ORCID Profile
0000-0001-6079-1316
Current Organisations
Prince Charles Hospital
,
Queensland University of Technology (QUT)
,
Medical Engineering Research Facility, Queensland University of Technology
,
Holy Spirit Northside Private Hospital
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Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.CLINBIOMECH.2007.05.009
Abstract: One of the known characteristics of osteoarthritis is the loss of articular cartilage lipids. Therefore, it is important to study how lipids influence the functions of the tissue. This can only be done successfully by indirect analysis involving the extraction of lipids and subsequent assessment of the delipidized matrix. Therefore, for accuracy, the procedure for lipid extraction must not induce any other modification in the s les to be assessed. Hence, we compare three rinsing agents and methods in this study. Normal and delipidized articular cartilage s les were tested under compressive loading at 4 loading velocities to obtain and compare their stiffness values. Chloroform rinsing resulted in a 45% decrease in the stiffness of cartilage at low strain-rates (10(-2)/s and 10(-1)/s) on average with a corresponding increase of 55% at higher strain-rate of 10/s relative to the normal. Ethanol rinsed cartilage exhibited a corresponding decrease of 40% at the low strain-rates while exhibiting an increase of about 20% at the highest loading rates. Propylene glycol rinsing resulted in a decrease of approximately 20% in stiffness, while an increase of up to 5% at high rates of loading. The loss of lipids modifies the stiffness of articular cartilage at all loading rates. The relatively larger deviation of the stiffness of chloroform-rinsed s les relative to the normal is probably a consequence of the drying process involved in rinsing protocol. It is probable that the results of milder rinsing agents, used without vacuum drying, are more reflective of physiological delipidization effects on the tissue. Consequently, we recommend propylene glycol and its associated protocol for extracting lipids from articular cartilage.
Publisher: The Journal of Rheumatology
Date: 15-01-2012
Abstract: Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMP), play key roles in development of osteoarthritis (OA). We investigated if crosstalk between subchondral bone osteoblasts (SBO) and articular cartilage chondrocytes (ACC) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, and also tested the possible involvement of mitogen-activated protein kinase (MAPK) signaling pathway during this process. ACC and SBO were isolated from normal and OA patients. An in vitro coculture model was developed to study the regulation of ADAMTS and MMP under normal and OA joint crosstalk conditions. The MAPK-ERK inhibitor PD98059 was applied to delineate the involvement of specific pathways during this interaction process. Indirect coculture of OA SBO with normal ACC resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3, and MMP-9 in ACC, whereas coculture of OA ACC led to increased MMP-1 and MMP-2 expression in normal SBO. Upregulation of ADAMTS and MMP under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway, and addition of the MAPK-ERK inhibitor PD98059 reversed the overexpression of ADAMTS and MMP in cocultures. These results add to the evidence that in human OA, altered bidirectional signals between SBO and ACC significantly influence the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMP. We have demonstrated for the first time that this altered crosstalk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.ARTH.2012.11.003
Abstract: Patients presenting for knee replacement on warfarin for medical reasons often require higher levels of anticoagulation peri-operatively than primary thromboprophylaxis and may require bridging therapy with heparin. We performed a retrospective case control study on 149 consecutive primary knee arthroplasty patients to investigate whether anti-coagulation affected short-term outcomes. Specific outcome measures indicated significant increases in prolonged wound drainage (26.8% of cases vs 7.3% of controls, P<0.001) superficial infection (16.8% vs 3.3%, P<0.001) deep infection (6.0% vs 0%, P<0.001) return-to-theatre for washout (4.7% vs 0.7%, P=0.004) and revision (4.7% vs 0.3%, P=0.001). Management of patients on long-term warfarin therapy following TKR is particularly challenging, as the surgeon must balance risk of thromboembolism against post-operative complications on an in idual patient basis in order to optimise outcomes.
Publisher: Medical Journals Sweden AB
Date: 08-12-2010
Publisher: Wiley
Date: 13-10-2017
Publisher: Wiley
Date: 17-12-2013
DOI: 10.1002/JCB.24362
Abstract: Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.
Publisher: Springer Science and Business Media LLC
Date: 27-10-2014
DOI: 10.1007/S11010-013-1840-2
Abstract: Recently, it has been suggested osteocytes control the activities of bone formation (osteoblasts) and resorption (osteoclast), indicating their important regulatory role in bone remodelling. However, to date, the role of osteocytes in controlling bone vascularisation remains unknown. Our aim was to investigate the interaction between endothelial cells and osteocytes and to explore the possible molecular mechanisms during angiogenesis. To model osteocyte/endothelial cell interactions, we co-cultured osteocyte cell line (MLOY4) with endothelial cell line (HUVECs). Co-cultures were performed in 1:1 mixture of osteocytes and endothelial cells or by using the conditioned media (CM) transfer method. Real-time cell migration of HUVECs was measured with the transwell migration assay and xCELLigence system. Expression levels of angiogenesis-related genes were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of vascular endothelial growth factor (VEGF) and mitogen-activated phosphorylated kinase (MAPK) signaling were monitored by western blotting using relevant antibodies and inhibitors. During the bone formation, it was noted that osteocyte dendritic processes were closely connected to the blood vessels. The CM generated from MLOY4 cells-activated proliferation, migration, tube-like structure formation, and upregulation of angiogenic genes in endothelial cells suggesting that secretory factor(s) from osteocytes could be responsible for angiogenesis. Furthermore, we identified that VEGF secreted from MLOY4-activated VEGFR2-MAPK-ERK-signaling pathways in HUVECs. Inhibiting VEGF and/or MAPK-ERK pathways abrogated osteocyte-mediated angiogenesis in HUVEC cells. Our data suggest an important role of osteocytes in regulating angiogenesis.
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/03008200902836057
Abstract: Many wounds to both soft and hard tissues heal via the formation of a granulation tissue bed. This bed is supportive of neoangiogenesis and releases proangiogenic, migratory, and proliferative growth factors and cytokines. In this study granulation tissue was grown on an intraperitoneal implant (4 mm diameter, 20 mm length) in a sheep. After 2 weeks, this implant was removed and transplanted into a femoral bone defect (4 mm diameter, 20 mm length). The sheep were sacrificed after 3 months, and the implant site examined using micro-CT and histology. A bone plaque formed adjacent to the implant, only in the presence of the peritoneal granulation tissue. This suggests that the formation of granulation tissue is a relatively conserved response at various locations in the body and its transplantation from one location to another can be used to induce tissue healing. This technique may prove useful as a method of improving physiological response to biomaterials.
Publisher: Elsevier BV
Date: 09-2007
DOI: 10.1016/J.ARTH.2006.09.013
Abstract: The effect of the incorporation of hotericin B into bone cement was examined as literature suggests, this may be a feasible method for the treatment of periprosthetic fungal infections. Addition of antifungal increased the compressive strength of the bone cement--a statistically significant amount from 107 +/- 2.3 to 121 +/- 1.5 MPa. Elution of tobramycin and hotericin B was quantified using ultraviolet-visible spectroscopy. Spectroscopy showed that 18% of the antibiotic was released during the first week, with most released in the first 24 hours. The elution of antifungal, however, was unable to be detected after 1 week, with less than 0.03% released. Amphotericin B does not weaken bone cement. Its inability to be delivered at a clinically significant dose gives no clear indication for its incorporation into cement.
Publisher: Elsevier
Date: 2009
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.BIOMATERIALS.2009.09.013
Abstract: To enhance and regulate cell affinity for poly (L-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (L-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (L-lactide)-block-poly (L-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-04-2019
Abstract: Computer navigation and image-derived instrumentation (IDI) are technology-based methods developed to improve outcomes and potentially reduce revision total knee arthroplasty (TKA). IDI refers to the use of manufactured, patient-specific surgical jigs. Conflicting reports exist on IDI-associated improvements in outcomes. The primary aim of the current study was to compare the rates of revision among TKA cases in which components were initially implanted with use of IDI, computer navigation, or neither of these methods (“other” TKA). The secondary aim was to determine whether the outcomes of IDI differed for specific subgroups. Data were obtained from the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) for the 3 TKA groups: IDI, computer-navigated, and other TKA. The study period was from the first IDI procedure recorded by the AOANJRR (April 2010) to December 31, 2016. The analysis was restricted to primary TKA cases undertaken for osteoarthritis and involving patellar resurfacing and the use of a cross-linked polyethylene insert. Subanalyses were performed to evaluate the effects of age, sex, implantation method, IDI manufacturer, prosthetic design, and prosthesis type on the rates of revision. Kaplan-Meier estimates of survivorship described the time to first revision. Hazard ratios (HRs, Cox proportional hazards models) with adjustment for age and sex were used to compare revision rates. IDI was used in 5,486 primary TKA procedures. There was no significant difference among the groups in the cumulative percent revision (CPR) at 5 years: 3.3% (95% confidence interval [CI], 2.4% to 4.6%) for IDI, 2.4% (95% CI, 2.2% to 2.7%) for the computer-navigated group, and 2.5% (95% CI, 2.3% to 2.7%) for other TKA. Posterior-stabilized TKA with use of the IDI method had a significantly higher rate of revision at months (HR, 1.45 [95% CI, 1.02 to 2.04] p = 0.036), as did IDI TKA in the ≤65-year-old patient cohort (HR, 1.52 [95% CI, 1.10 to 2.09] p = 0.010), compared with computer-navigated TKA. Patellar revision was significantly more likely in the IDI group. IDI TKA demonstrated no overall difference in early to mid-term revision rates compared with standard implantation methods. However, elevated rates of revision were seen with posterior-stabilized TKA, in patients ≤65 years of age, and for patellar revision, meaning that this method should be used with some caution and requires further study. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
Publisher: Mary Ann Liebert Inc
Date: 08-2011
DOI: 10.1089/TEN.TEC.2010.0453
Abstract: For a scaffold material to be considered effective and efficient for tissue engineering, it should be biocompatible and bioinductive. Silk fiber is a natural biocompatible material suitable for scaffold fabrication however, silk is tissue conductive and lacks tissue-inductive properties. One proposed method to make the scaffold tissue inductive is to introduce plasmids or viruses encoding a specific growth factor into the scaffold. In this study, we constructed adenoviruses encoding bone morphogenetic protein-7 (BMP-7) and incorporated these into silk scaffolds. The osteoinductive and new bone formation properties of these constructs were assessed in vivo in a critical-sized skull defect animal model. Silk fibroin scaffolds containing adenovirus particles coding BMP-7 were prepared. The release of the adenovirus particles from the scaffolds was quantified by tissue-culture infective dose (TCID50), and the bioactivity of the released viruses was evaluated on human bone marrow mesenchymal stromal cells (BMSCs). To demonstrate the in vivo bone forming ability of the virus-carrying silk fibroin scaffold, the scaffold constructs were implanted into calvarial defects in SCID mice. In vitro studies demonstrated that the virus-carrying silk fibroin scaffold released virus particles over a 3-week period while preserving their bioactivity. In vivo test of the scaffold constructs in critical-sized skull defect areas revealed that silk scaffolds were capable of delivering the adenovirus encoding BMP-7, resulting in significantly enhanced new bone formation. Silk scaffolds carrying BMP-7 encoding adenoviruses can effectively transfect cells and enhance both in vitro and in vivo osteogenesis. The findings of this study indicate that silk fibroin is a promising biomaterial for gene delivery to repair critical-sized bone defects.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4TB00009A
Abstract: Most research virtually ignores the important role of a blood clot in supporting bone healing.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.ARTH.2008.09.018
Abstract: Hip navigation was used as an assessment tool to compare ability to reproduce trial and definitive acetabular placement in total hip arthroplasty, using cemented and uncemented components. We demonstrated a significant difference in reproducibility between components. Of 20 uncemented cups, 4 (20%) deviated from the target inclination by 5 degrees or more compared to none of 21 in the cemented group (P = .048). Of the 20 uncemented cups, 7 (35%) deviated from the target version by 5 degrees or more compared to none of 21 in the cemented group (P = .003). This may explain higher rates of revision for dislocation with uncemented components. There was also a significant difference between the groups with regard to deviation from planned leg length (P < .001).
Publisher: Springer Science and Business Media LLC
Date: 17-06-2009
Abstract: There is little scientific evidence to support the usual practice of providing outpatient rehabilitation to patients undergoing total knee replacement surgery (TKR) immediately after discharge from the orthopaedic ward. It is hypothesised that the lack of clinical benefit is due to the low exercise intensity tolerated at this time, with patients still recovering from the effects of major orthopaedic surgery. The aim of the proposed clinical trial is to investigate the clinical and cost effectiveness of a novel rehabilitation strategy, consisting of an initial home exercise programme followed, approximately six weeks later, by higher intensity outpatient exercise classes. In this multicentre randomised controlled trial, 600 patients undergoing primary TKR will be recruited at the orthopaedic pre-admission clinic of 10 large public and private hospitals in Australia. There will be no change to the medical or rehabilitative care usually provided while the participant is admitted to the orthopaedic ward. After TKR, but prior to discharge from the orthopaedic ward, participants will be randomised to either the novel rehabilitation strategy or usual rehabilitative care as provided by the hospital or recommended by the orthopaedic surgeon. Outcomes assessments will be conducted at baseline (pre-admission clinic) and at 6 weeks, 6 months and 12 months following randomisation. The primary outcomes will be self-reported knee pain and physical function. Secondary outcomes include quality of life and objective measures of physical performance. Health economic data (health sector and community service utilisation, loss of productivity) will be recorded prospectively by participants in a patient diary. This patient cohort will also be followed-up annually for five years for knee pain, physical function and the need or actual incidence of further joint replacement surgery. The results of this pragmatic clinical trial can be directly implemented into clinical practice. If beneficial, the novel rehabilitation strategy of utilising outpatient exercise classes during a later rehabilitation phase would provide a feasible and potentially cost-effective intervention to optimise the physical well-being of the large number of people undergoing TKR. ACTRN12609000054213
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.ARTH.2007.07.009
Abstract: Risk factors were investigated for revision for dislocation in primary total hip arthroplasties (THAs) between September 1, 1999, and December 31, 2004, as reported by the Australian Orthopaedic Association National Joint Replacement Registry. For 65992 primary THAs, the only initial diagnoses with significantly increased relative risk (RR) of revision for dislocation compared to osteoarthritis were fractured neck of femur (RR, 2.03 P < .001), rheumatoid arthritis (RR, 2.01 P < .01), and avascular necrosis (RR, 1.57 P < .05). A total of 58109 primary THAs for osteoarthritis were investigated for effect of age group, sex, and fixation method. There were 428 (0.7%) revisions for dislocation, 369 (0.8%) with a cementless acetabulum, and 59 (0.6%) with cemented acetabulum (RR, 1.59 P < .01). There is a significantly increasing risk of revision for dislocation as head size decreases (P < .001). Cementless acetabula, particularly with smaller heads, have a higher rate of revision for dislocation.
Publisher: Springer Science and Business Media LLC
Date: 26-05-2018
DOI: 10.1007/S40271-018-0315-7
Abstract: A wealth of peer-reviewed data exists regarding people's health experience, yet practical ways of using the data to understand patients' experiences and to inform health co-design are needed. This study aims to develop an applied and pragmatic method for using patient experience literature in co-design by transforming it into an accessible and creative co-design tool. A scoping literature review of the CINAHL, MEDLINE, PsycINFO and PubMed electronic databases was conducted from January 2011 through August 2016. Qualitative publications regarding the experience of living with diabetes in Australia were selected. The Results section of each paper was extracted and affinity analysis was applied to identify insights into the health experience. These insights were developed into a card tool for use in health co-design activities. Thirteen relevant papers were identified from the review, and affinity analysis of the Results sections of these papers lead to the identification of 85 insights, from 'Shock of diagnosis' (Insight 1), to 'Delay seeking care' (Insight 9), to 'Assess the quality of care' (Insight 28), to 'Avoid or adapt habits' (Insight 78). Each insight was developed into an in idual card, which included a high-level theme, insight, quote and a link back to the literature, together making up the Health Experience Insight Cards, Living with Diabetes Edition. This was the first study to develop a method for transforming existing patient experience literature into a creative tool for health improvement. The Health Experience Insight Cards collate the erse experiences of over 300 people living with diabetes in Australia, from 13 studies. Health improvement teams can use the 'Living with Diabetes Edition' cards or they can follow this pragmatic method to create their own cards focused on other health experiences to facilitate person-focused health improvements.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 10-2023
Publisher: Wiley
Date: 16-09-2016
DOI: 10.1002/ACR.22861
Abstract: To evaluate the prevalence and determinants of clinically important fatigue before and up to 12 months after total knee replacement (TKR) surgery. This study was a secondary analysis of a prospective cohort study conducted among 422 patients (ages 45-74 years) undergoing primary TKR for osteoarthritis (OA) who participated in the Maximum Recovery After Knee Replacement randomized clinical trial. Assessments were carried out before, and at 6 weeks, 6 months, and 12 months after surgery. Self-reported fatigue was assessed on a 10-cm visual analog scale. Patients also completed a number of questionnaires evaluating knee pain, activity limitations, psychological well-being, comorbidity, and physical activity. Linear regression analyses were conducted to explore 6- and 12-month cross-sectional and longitudinal associations with self-reported fatigue. Clinically important fatigue (≥6.7 of 10) was reported by 145 patients (34%) before surgery, decreasing to 14%, 12%, and 8% at 6 weeks, 6 months, and 12 months after surgery, respectively. In multivariate analyses, muscle strength was strongly associated with fatigue at 6 months, and knee pain, activity limitations, number of comorbidities, and lack of energy were strongly associated with fatigue at both 6 and 12 months after TKR surgery. Female sex, number of comorbidities, depression, and fatigue were all early predictors of fatigue 12 months after TKR. Among patients undergoing TKR for OA, clinically important fatigue is considerably prevalent both before and for at least 6 months after surgery. Identifying and addressing early predictors of ongoing fatigue has the potential to improve the quality of life following TKR surgery.
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.ARTH.2008.02.014
Abstract: Cement-within-cement (C-C) revision arthroplasty minimizes the complications associated with removal of secure polymethylmethacrylate. Failure at the interfacial region between new and old cement mantles remains a theoretical concern. This article assesses the cyclic fatigue properties of bilaminar cement mantles after C-C revision in vitro with the Exeter stem. Seven Exeter stems were cemented into Sawbone femurs and removed, and new undersized stems were cemented into the preserved mantle. The new constructs were loaded for 1,000,000 cycles at body temperature. Cement mantles were inspected postcycling. In no case was there delamination or failure of the cement mantle. The findings support the hypothesis that use of a thin revision cement mantle in conjunction with a polished double-tapered stem is not detrimental to the overall success of the implant. In the presence of a secure cement-bone interface in suitable patients, we recommend C-C revision techniques using double-tapered polished femoral stems.
Publisher: SAGE Publications
Date: 02-2007
Abstract: The mechanical properties of the short glass fibre reinforced (SGFR) epoxy resin used as the cortical bone analogue in the third-generation Sawbones femurs were investigated for use within orthopaedic benchtop tests. Tensile and four-point bending tests were used to assess the material properties of the SGFR epoxy at both room (22° C) and body temperatures (37° C). The 20 standardized specimens used for the materials testing were machined from third-generation Sawbones femurs. The flexural properties of the specimens were determined using ASTM D6272-02 and the tensile properties were obtained using ASTM D638-02. The mean (and standard deviation, or SD) values of the modulus of elasticity in four-point bending for room and body temperature specimens of 7.8 (0.64) GPa and 2.8 (0.66) GPa respectively were significantly different ( P 0.001). The mean (and SD) values of the modulus of elasticity in tension for the room and body temperature specimens of 9.4 (0.8) GPa and 5.4 (1.3) GPa respectively were also significantly different ( P = 0.02). The modulus of elasticity of SGFR epoxy is highly temperature dependent. A reduction in the modulus of elasticity of up to 63 per cent was observed when increasing the temperature of the specimens from room to body temperature. SGFR epoxy Sawbones do not accurately represent the material properties of bone at body temperature.
Publisher: Springer Science and Business Media LLC
Date: 18-04-2017
DOI: 10.1038/SREP46457
Abstract: The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA, C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0). The aim of this study was to investigate whether diets containing in idual SFA together with excess simple carbohydrates induce osteoarthritis (OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats were given either a corn starch diet or a diet composed of simple carbohydrates together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also exhibited cartilage degradation and subchondral bone changes similar to OA. In contrast, replacement of beef tallow with LA decreased signs of metabolic syndrome together with decreased cartilage degradation. Furthermore, PA and SA but not LA increased release of matrix sulphated proteoglycans in cultures of bovine cartilage explants or human chondrocytes. In conclusion, we have shown that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like knee changes. Thus, diets containing SFA are strongly relevant to the development or prevention of both OA and metabolic syndrome.
Publisher: Oxford University Press (OUP)
Date: 12-01-2012
DOI: 10.1093/RHEUMATOLOGY/KER360
Abstract: The p38 mitogen-activated protein kinase (MAPK) signal transduction pathway is involved in a variety of inflammatory responses, including cytokine generation, cell differentiation proliferation and apoptosis. Here, we examined the effects of systemic p38 MAPK inhibition on cartilage cells and OA disease progression by both in vitro and in vivo approaches. p38 kinase activity was evaluated in normal and OA cartilage cells by measuring the amount of phosphorylated protein. To examine the function of p38 signalling pathway in vitro, normal chondrocytes were isolated and differentiated in the presence or absence of p38 inhibitor SB203580 and analysed for chondrogenic phenotype. Effect of systemic p38 MAPK inhibition in normal and OA (induced by menisectomy) rats were analysed by treating animals with vehicle alone [dimethylsulphoxide (DMSO)] or p38 inhibitor (SB203580). Damage to the femur and tibial plateau was evaluated by modified Mankin score, histology and immunohistochemistry. Our in vitro studies have revealed that a down-regulation of chondrogenic and an increase of hypertrophic gene expression occurs in the normal chondrocytes when p38 is neutralized by a pharmacological inhibitor. We further observed that the basal levels of p38 phosphorylation were decreased in OA chondrocytes compared with normal chondrocytes. These findings together indicate the importance of this pathway in the regulation of cartilage physiology and its relevance to OA pathogenesis. At the in vivo level, systematic administration of a specific p38 MAPK inhibitor, SB203580, continuously for more than a month led to a significant loss of proteoglycan, aggrecan and cartilage thickness. On the other hand, SB203580-treated normal rats showed a significant increase in Terminal dUTP nick end-labelling (TUNEL)-positive cells, cartilage hypertrophy markers such as Type 10 collagen, Runt-related transcription factor and MMP-13 and substantially induced OA-like phenotypic changes in the normal rats. In addition, menisectomy-induced OA rat models that were treated with p38 inhibitor showed aggravation of cartilage damage. In summary, this study has provided evidence that the component of the p38 MAPK pathway is important to maintain cartilage health, and its inhibition can lead to severe cartilage degenerative changes. The observations in this study highlight the possibility of using activators of the p38 pathway as an alternative approach in the treatment of OA.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.BIOMATERIALS.2015.04.044
Abstract: Osteoblast lineage cells are direct effectors of osteogenesis and are, therefore, commonly used to evaluate the in vitro osteogenic capacity of bone substitute materials. This method has served its purposes when testing novel bone biomaterials however, inconsistent results between in vitro and in vivo studies suggest the mechanisms that govern a material's capacity to mediate osteogenesis are not well understood. The emerging field of osteoimmunology and immunomodulation has informed a paradigm shift in our view of bone biomaterials-from one of an inert to an osteoimmunomodulatory material-highlighting the importance of immune cells in materials-mediated osteogenesis. Neglecting the importance of the immune response during this process is a major shortcoming of the current evaluation protocol. In this study we evaluated a potential angiogenic bone substitute material cobalt incorporated with β-tricalcium phosphate (CCP), comparing the traditional "one cell type" approach with a "multiple cell types" approach to assess osteogenesis, the latter including the use of immune cells. We found that CCP extract by itself was sufficient to enhance osteogenic differentiation of bone marrow stem cells (BMSCs), whereas this effect was cancelled out when macrophages were involved. In response to CCP, the macrophage phenotype switched to the M1 extreme, releasing pro-inflammatory cytokines and bone catabolic factors. When the CCP materials were implanted into a rat femur condyle defect model, there was a significant increase of inflammatory markers and bone destruction, coupled with fibrous encapsulation rather than new bone formation. These findings demonstrated that the inclusion of immune cells (macrophages) in the in vitro assessment matched the in vivo tissue response, and that this method provides a more accurate indication of the essential role of immune cells when assessing materials-stimulated osteogenesis in vitro.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2016
Publisher: Springer Science and Business Media LLC
Date: 11-03-2013
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.INJURY.2009.01.116
Abstract: The use of allograft bone is increasingly common in orthopaedic reconstruction procedures. The optimal method of preparation of allograft bone is subject of great debate. Proponents of fresh-frozen graft cite improved biological and biomechanical characteristics relative to irradiated material, whereas fear of bacterial or viral transmission warrants some to favour irradiated graft. Careful review of the literature is necessary to appreciate the influence of processing techniques on bone quality. Whereas limited clinical trials are available to govern the selection of appropriate bone graft, this review presents the argument favouring the use of fresh-frozen bone allograft as compared to irradiated bone.
Publisher: Wiley
Date: 27-01-2015
DOI: 10.1002/ACR.22457
Abstract: To determine, at 6 weeks postsurgery, if a monitored home exercise program (HEP) is not inferior to usual care rehabilitation for patients undergoing primary unilateral total knee replacement (TKR) surgery for osteoarthritis. We conducted a multicenter, randomized clinical trial. Patients ages 45-75 years were allocated at the time of hospital discharge to usual care rehabilitation (n = 196) or the HEP (n = 194). Outcomes assessed 6 weeks after surgery included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales, knee range of motion, and the 50-foot walk time. The upper bound of the 95% confidence interval (95% CI) mean difference favoring usual care was used to determine noninferiority. At 6 weeks after surgery there were no significant differences between usual care and HEP, respectively, for pain (7.4 and 7.2 95% CI mean difference [MD] -0.7, 0.9), physical function (22.5 and 22.4 95% CI MD -2.5, 2.6), knee flexion (96° and 97° 95% CI MD -4°, 2°), knee extension (-7° and -6° 95% CI MD -2°, 1°), or the 50-foot walk time (12.9 and 12.9 seconds 95% CI MD -0.8, 0.7 seconds). At 6 weeks, 18 patients (9%) allocated to usual care and 11 (6%) to the HEP did not achieve 80° knee flexion. There was no difference between the treatment allocations in the number of hospital readmissions. The HEP was not inferior to usual care as an early rehabilitation protocol after primary TKR.
Publisher: American Chemical Society (ACS)
Date: 09-12-2009
DOI: 10.1021/BM800937G
Abstract: Amphiphilic triblock copolymers of methoxy-poly(ethylene glycol)-poly(L-lactide)-poly(L-lysine) (MPEG-b-PLLA-b-PLL) (Mn=8540-22 240) were synthesized through the ring-opening polymerization of Nepsilon-(Z)-lysine-N-carboxyanhydrides (N(epsilon)-(Z)-Lys-NCA) using MPEG-b-PLLA-NH2 as a macroinitiator. The triblock copolymers and diblock precursors were characterized by 1H NMR, ATR-FTIR, and GPC. The chain lengths of each block could be controlled by varying the feed ratios of the monomers. The surface properties of films of PLLA modified by blending with the triblock copolymers were investigated by XPS and AFM and demonstrated an enrichment of PLL blocks on the surface of the PLLA film. No cytotoxicity was detected on a range of modified PLLA films arising from the incorporation of the triblock copolymers. The triblock copolymers MPEG-b-PLLA-b-PLL showed better surface properties in promoting osteoblast adhesion and proliferation compared with pure PLLA and PLLA modified with MPEG-b-PLLA diblock copolymers. This study demonstrated that the triblock copolymers containing free amino groups, which self-segregate on the surface of biodegradable polyesters, have potential for applications in cell delivery and tissue engineering.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JOCA.2016.06.005
Abstract: Hypoxia is known to stabilize hypoxia-inducible factor (HIF) and initiate angiogenic signaling cascade. However, cartilage living in hypoxia environment can maintain avascularity. It is well known that abrogation of avascularity is related to cartilage degradation in osteoarthritis (OA). The aims of present study were to investigate the role of chondromodulin-1 (ChM-1), an endogenously anti-angiogenic protein in cartilage, during chondrocyte maturation and OA progression, as well as to explore the molecular mechanisms underlying the function of ChM-1 with a focus on HIF-2α pathway. Angiogenic-related markers were evaluated in OA cartilage and different stages of chondrocyte differentiation. Chondrocytes transfected with ChM-1 lentivirus or siRNA was treated with tumor necrosis factor (TNF-α) to investigate the role of ChM-1 in chondrocyte hypertrophic changes. In vivo study was conducted by using a surgical induced OA rat model with intra-articular injection of lentivirus ChM-1 (LV-ChM-1) or mock lentivirus (LV-GFP) control. Transcriptional activity of HIF-2α was determined by chromatin immunoprecipitation (ChIP) assay to unveil the mechanisms of ChM-1. Majority angiogenic factors increased in severe OA cartilage, while anti-angiogenic factors including ChM-1 decreased. ChM-1 expression was strongly related with chondrocyte differentiation and chondrogenesis in vitro. ChM-1 overexpression protected chondrocytes from TNF-α induced hypertrophy, and intra-articular injection of LV-ChM-1 delayed OA progression. ChM-1 delayed HIF-2α nuclear translocation at early time-points and decreased transcriptional activity of HIF-2α on collagen type Х α1 (COL10A1), vascular endothelial growth factor A (VEGFA) and matrix metallopeptidase-13 (MMP-13). ChM-1 maintains cartilage homeostasis by inhibiting HIF-2α induced catabolic activity and regulation of ChM-1 in cartilage may be a promising therapeutic strategy for OA.
Publisher: Wiley
Date: 14-07-2010
DOI: 10.1002/JBM.A.32843
Abstract: Impaction bone grafting in revision arthroplasty is a common and successful procedure to restore primary bone stock. Reducing the amount of bone needed to fill large grafts has been a driving force for the use of synthetic materials that can act as extenders or substitutes. To this end, we evaluated the mechanical properties of a new class of biodegradable polymer beads with and without donor bone to determine its suitability for use in impaction grafting. Biodegradable methacrylated anhydride beads were synthesized using thermal polymerization techniques. The mechanical properties of the beads were then tested in an impaction grafting test chamber and compared with morsellised porcine allograft. The beads, porcine allograft and a 50/50 combination all had similar mechanical properties, both in compression and relaxation. Pure polymer beads compacted significantly less than pure allograft and retained macroporosity after impaction. Our results suggest that the biodegradable beads have sufficient mechanical properties to be considered as an impaction grafting substitute or extender. Their ability to fill space whilst retaining macroporosity may be advantageous for tissue ingrowth and remodeling.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2015
DOI: 10.1007/S00402-015-2172-3
Abstract: The risk for late periprosthetic femoral fractures is higher in patients treated for a neck of femur fracture compared to osteoarthritis. It has been hypothesised that osteopaenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated whether a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite Sawbone model. A biomechanical bone analogue was used. Two different body sizes (Exeter 44-1 versus 44-4) of a polished tapered cemented femoral stem were implanted by an experienced surgeon in seven bone analogues each and internally rotated at 40°/s until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874, MI, USA). The data were non-parametric and therefore tested with the Mann-Whitney U test. The median torque to fracture was 156.7 Nm (IQR 19.7) for the 44-1 stem and 237.1 Nm (IQR 52.9) for the 44-4 stem (p = 0.001). The median fracture energy was 8.5 J (IQR 7.3) for the 44-1 stem and 19.5 J (IQR 8.8) for the 44-4 stem (p = 0.014). The use of large body polished tapered cemented stems for neck of femur fractures increases the torque to failure in a biomechanical model and therefore is likely to reduce late periprosthetic fracture risk in this vulnerable cohort.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.BIOMATERIALS.2010.01.083
Abstract: The periosteum plays an indispensable role in both bone formation and bone defect healing. In this study we constructed an artificial in vitro periosteum by incorporating osteogenic differentiated bone marrow stromal cells (BMSCs) and cobalt chloride (CoCl(2))-treated BMSCs. The engineered periostea were implanted both subcutaneously and into skull bone defects in SCID mice to investigate ectopic and orthotopic osteogenesis and vascularization. After two weeks in subcutaneous and four weeks in bone defect areas, the implanted constructs were assessed for ectopic and orthotopic osteogenesis and vascularization by micro-CT, histomorphometrical and immunohistochemical methods. The results showed that CoCl(2) pre-treated BMSCs induced higher degree of vascularization and enhanced osteogenesis within the implants in both ectopic and orthotopic areas. This study provided a novel approach using BMSCs sourced from the same patient for both osteogenic and pro-angiogenic purposes in constructing tissue engineered periosteum to enhance vascularized osteogenesis.
Publisher: Elsevier BV
Date: 10-2002
Abstract: There is concern that modularity in a total hip arthroplasty system increases serum cobalt and chromium ion levels. This study measures the serum cobalt and chromium levels in patients with an Oxford Universal Hip (Corin, Cirencester, United Kingdom), which has a modular sliding mechanism patients with a similarly manufactured hip with no sliding mechanism and a control group. Loosening was excluded clinically and radiologically. Arthroplasty patients had statistically higher levels of serum cobalt and chromium than controls, but there was no significant difference in levels between the implanted groups.
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1016/J.ARTH.2006.04.010
Abstract: Although cement-within-cement revision arthroplasty minimizes the complications associated with removal of secure PMMA, failure at the interfacial region between new and old cement mantles remains a theoretical concern. This article assesses the variability in shear properties of bilaminar cement mantles related to duration of postcure and the use of antibiotic cements. Bilaminar cement mantles were 15% to 20% weaker than uniform mantles (P < .001) and demonstrated variability in shear strength related to duration of postcure of the freshly applied cement (P < .001). The use of Antibiotic Simplex did not significantly influence interfacial cement adhesion (P = .52). Interfacial adhesion by mechanisms other than mechanical interlock plays a significant role in the bond formed between new and old PMMA cements, with an important contribution by diffusion-based molecular interdigitation. In the presence of a secure cement-bone interface, we recommend cement-within-cement revision techniques in suitable patients.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2013
DOI: 10.1038/NCOMMS2905
Abstract: Small interfering RNA silences specific genes by interfering with mRNA translation, and acts to modulate or inhibit specific biological pathways a therapy that holds great promise in the cure of many diseases. However, the naked small interfering RNA is susceptible to degradation by plasma and tissue nucleases and due to its negative charge unable to cross the cell membrane. Here we report a new polymer carrier designed to mimic the influenza virus escape mechanism from the endosome, followed by a timed release of the small interfering RNA in the cytosol through a self-catalyzed polymer degradation process. Our polymer changes to a negatively charged and non-toxic polymer after the release of small interfering RNA, presenting potential for multiple repeat doses and long-term treatment of diseases.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6NR06421C
Abstract: The osteoimmune environment plays indispensable roles in bone regeneration because the early immune environment that exists during the regenerative process promotes the recruitment and differentiation of osteoblastic lineage cells. The response of immune cells growing on nanotopographic surfaces and the microenvironment they generate should be considered when evaluating nanotopography-mediated osteogenesis, which are topics that are generally neglected in the field. In this study, we investigated the modulatory effects of nanoporous anodic alumina with different sized pores on macrophage responses and their subsequent effects on the osteogenic differentiation of bone marrow stromal cells (BMSCs). The nanopore structure and the pore size were found to be important adhesive cues for macrophages, which affected their spreading and cell shape, subsequently regulated the expression and activation of autophagy pathway components (LC3A/B, Beclin-1, Atg3, Atg7, and P62) and modulated the inflammatory response, osteoclastic activities, and release of osteogenic factors. Subsequently, the osteogenic pathways (Wnt and BMP) of BMSCs were found to be regulated by different nanopore-induced inflammatory environments, which affected the osteogenic differentiation outcomes. This study is the first to emphasize the effects of immune cells on nanotopography-mediated osteogenesis, which could lead to a new strategy for the development of advanced nanobiomaterials for tissue engineering, nanomedicine and immunotherapeutic applications.
Publisher: Medical Journals Sweden AB
Date: 05-09-2015
Publisher: Wiley
Date: 24-03-2016
DOI: 10.1002/ACR.22692
Abstract: To determine the prevalence and burden of pain and activity limitations associated with retaining presurgery self-reported knee instability 6 months after total knee replacement (TKR) surgery and to identify early potentially modifiable risk factors for retaining knee instability in the operated knee after TKR surgery. A secondary analysis was performed using measures obtained from 390 participants undergoing primary unilateral TKR and participating in a randomized clinical trial. Self-reported knee instability was measured using 2 items from the Activities of Daily Living Scale of the Knee Outcome Survey. Outcome measures were knee pain (range 0-20) and physical function (range 0-68) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC), stair-climb power, 50-foot walk time, knee range of motion, and isometric knee flexion and extension strength. In this study, 72% of participants reported knee instability just prior to surgery, with 32% retaining instability in the operated knee 6 months after surgery. Participants retaining operated knee instability had significantly more knee pain and activity limitations 6 months after surgery, with mean ± SD WOMAC scores of 4.8 ± 3.7 and 17.5 ± 11.1, respectively, compared to participants without knee instability, with 2.9 ± 3.1 and 9.8 ± 9.2. The multivariable predictor model for retained knee instability included a high comorbidity score (>6), low stair-climb power ( 7 of 20), and younger age (<60 years). Self-reported knee instability is highly prevalent before and after TKR surgery and is associated with a considerable burden of pain and activity limitation in the operated knee. Increasing lower extremity muscle power may reduce the risk of retaining knee instability after TKR surgery.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2023
Publisher: Mary Ann Liebert Inc
Date: 02-2010
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.ARTH.2016.02.023
Abstract: The incidence of obesity among patients presenting for elective total hip arthroplasty (THA) has increased in the last decade, and the relationship between obesity and the need for joint arthroplasty has been demonstrated. This study evaluates the effects of morbid obesity on outcomes after primary THA by comparing short-term outcomes in THA between a morbidly obese (body mass index [BMI] ≥40) and a normal weight (BMI, 18.5 to <25) cohort at our institution between January 2003 and December 2010. Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission, and length of readmission were compared. Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (P = .002). Postoperatively, there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI ≥40 compared with 2.7% (P = .005) as well as a 5.1-fold increase in surgery-related readmitted bed days-0.32 bed days per patient for normal weight compared with 1.64 bed days per patient for the morbidly obese (P = .026). Morbidly obese patients present a technical challenge and likely this, and the resultant complications are underestimated. More work needs to be performed to enable suitable allocation of resources.
Publisher: Wiley
Date: 19-02-2009
DOI: 10.1002/JCB.22088
Abstract: Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing MSC self-renewal and differentiation remain largely unknown. The development of sophisticated techniques, in particular clinical proteomics, has enabled researchers in various fields to identify and characterize cell specific biomarkers for therapeutic purposes. This study seeks to understand the cellular and sub-cellular processes responsible for the existence of stem cell populations in bone marrow s les by revealing the whole cell proteome of the clonal cultures of bone marrow-derived MSCs (BMSCs). Protein profiling of the MSC clonal populations was conducted by Two-Dimensional Liquid Chromatography/Matrix-Assisted Laser Desorption/Ionisation (MALDI) Mass Spectrometry (MS). A total of 83 proteins were identified with high confidence of which 11 showed differential expression between subpopulations, which included cytoskeletal and structural proteins, calcium binding proteins, cytokinetic proteins, and members of the intermediate filament family. This study generated a proteome reference map of BMSCs from the clonal populations, which will be valuable to better understand the underlying mechanism of BMSC self-renewal and differentiation.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.DIFF.2010.12.003
Abstract: Angiogenesis, or neovascularization, is a finely balanced process controlled by pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is a major pro-angiogenic factor, whereas pigment epithelial-derived factor (PEDF) is the most potent natural angiogenesis inhibitor. In this study, the regulatory role of bone marrow stromal cells (BMSCs) during angiogenesis was assessed by the endothelial differentiation potential, VEGF/PEDF production and responses to pro-angiogenic and hypoxic conditions. The in vivo regulation of blood vessel formation by BMSCs was also explored in a SCID mouse model. Results showed that PEDF was expressed more prominently in BMSCs compared to VEGF. This contrasted with human umbilical vein endothelial cells (HUVECs) where the expression of VEGF was higher than that of PEDF. The ratio of VEGF/PEDF gene expression in BMSCs increased when VEGF concentration reached 40ng/ml in the culture medium, but decreased at 80ng/ml. Under CoCl(2)-induced hypoxic conditions, the VEGF/PEDF ratio of BMSCs increased significantly in both normal and angiogenic culture media. There was no expression of endothelial cell markers in BMSCs cultured in either pro-angiogenic or hypoxia culture conditions when compared with HUVECs. The in vivo study showed that VEGF/PEDF expression closely correlated with the degree of neovascularization, and that hypoxia significantly induced pro-angiogenic activity in BMSCs. These results indicate that, rather than being progenitors of endothelial cells, BMSCs play an important role in regulating the neovascularization process, and that the ratio of VEGF and PEDF may, in effect, be an indicator of the pro- or anti-angiogenic activities of BMSCs.
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2020
DOI: 10.1101/2020.05.15.094847
Abstract: Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. The objective of this study was to characterize ovine BMSC (oBMSC) in vitro , and to evaluate the capacity of chondrogenic micro -pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation. oBMSC micro -pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O 2 . The capacity of cartilage micro -pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction medium ingredient, 3-Isobutyl-1-methylxanthine (IBMX) was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O 2 atmosphere. Micro -pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro -pellets. While oACh micro -pellets formed cartilage-like repair tissue in sheep, oBMSC micro -pellets did not. The sensitivity of oBMSC to IBMX highlights species-species differences between oBMSC and hBMSC. Micro -pellets manufactured from oBMSC were not effective in repairing osteochondral defects, while oACh micro -pellets enabled modest repair. While oBMSC can be driven to form cartilage-like tissue in vitro, their effective use in cartilage repair will require mitigation of hypertrophy.
Publisher: Springer Science and Business Media LLC
Date: 21-10-2016
DOI: 10.1038/SREP35645
Abstract: The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing.
Publisher: Georg Thieme Verlag KG
Date: 25-10-2022
DOI: 10.1055/A-1967-2346
Abstract: This study examines the potential cost savings for the health system and the community in a broadly accessible model through the increased utilization of unicompartmental knee arthroplasty (UKA) using robotic arm-assisted UKA (raUKA) versus conventional total knee arthroplasty (cTKA). We retrospectively reviewed 240 patients where the first 120 consecutive raUKA performed during this period were matched to 120 cTKAs. Clinical data from the medical records and costs for procedure for each component were collected. Bivariate analyses were performed on the data to determine if there were statistically significant differences by surgery type in clinical outcomes and financial costs. There was a significantly lower cost incurred for raUKA versus cTKA with an average saving of AU$7,179 per case. The operating time (86.0 vs. 75.9 minutes p = 0.004) was significantly higher for raUKA, but the length of stay was significantly lower (1.8 vs. 4.8 days p 0.001). There was a significant difference in the use of opioids between raUKA and cTKA (125.0 morphine equivalent [ME] vs. 522.1 ME, p 0.001). This study demonstrated that the use of raUKA rather than cTKA in suitably indicated patients may realize significant cost savings.
Publisher: Wiley
Date: 15-06-2015
DOI: 10.1002/JBMR.2445
Abstract: Canonical Wnt signaling is important in tooth development but it is unclear whether it can induce cementogenesis and promote the regeneration of periodontal tissues lost because of disease. Therefore, the aim of this study is to investigate the influence of canonical Wnt signaling enhancers on human periodontal ligament cell (hPDLCs) cementogenic differentiation in vitro and cementum repair in a rat periodontal defect model. Canonical Wnt signaling was induced by (1) local injection of lithium chloride (2) local injection of sclerostin antibody and (3) local injection of a lentiviral construct overexpressing β-catenin. The results showed that the local activation of canonical Wnt signaling resulted in significant new cellular cementum deposition and the formation of well-organized periodontal ligament fibers, which was absent in the control group. In vitro experiments using hPDLCs showed that the Wnt signaling pathway activators significantly increased mineralization, alkaline phosphatase (ALP) activity, and gene and protein expression of the bone and cementum markers osteocalcin (OCN), osteopontin (OPN), cementum protein 1 (CEMP1), and cementum attachment protein (CAP). Our results show that the activation of the canonical Wnt signaling pathway can induce in vivo cementum regeneration and in vitro cementogenic differentiation of hPDLCs.
Publisher: Wiley
Date: 21-04-2014
DOI: 10.1111/CLR.12178
Abstract: Titanium implant surfaces with modified topographies have improved osteogenic properties in vivo. However, the molecular mechanisms remain obscure. This study explored the signaling pathways responsible for the pro-osteogenic properties of micro-roughened (SLA) and chemically/nanostructurally (modSLA) modified titanium surfaces on human alveolar bone-derived osteoprogenitor cells (BCs) in vitro. The activation of stem cell signaling pathways (TGFβ/BMP, Wnt, FGF, Hedgehog, Notch) was investigated following early exposure (24 and 72 h) of BCs to SLA and modSLA surfaces in the absence of osteogenic cell culture supplements. Key regulatory genes from the TGFβ/BMP (TGFBR2, BMPR2, BMPR1B, ACVR1B, SMAD1, SMAD5), Wnt (Wnt/β-catenin and Wnt/Ca(2+) ) (FZD1, FZD3, FZD5, LRP5, NFATC1, NFATC2, NFATC4, PYGO2, LEF1) and Notch (NOTCH1, NOTCH2, NOTCH4, PSEN1, PSEN2, PSENEN) pathways were upregulated on the modified surfaces. These findings correlated with a higher expression of osteogenic markers bone sialoprotein (IBSP) and osteocalcin (BGLAP), and bone differentiation factors BMP2, BMP6, and GDF15, as observed on the modified surfaces. These findings demonstrate that the activation of the pro-osteogenic cell signaling pathways by modSLA and SLA surfaces leads to enhanced osteogenic differentiation as evidenced after 7 and 14 days culture in osteogenic media and provides a mechanistic insight into the superior osseointegration on the modified surfaces observed in vivo.
Publisher: Mary Ann Liebert Inc
Date: 09-2009
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.ARTH.2017.03.060
Abstract: It is increasingly apparent that the effect of obesity in arthroplasty is joint-specific. This study evaluates the effects of morbid obesity on primary total knee arthroplasty by comparing short-term outcomes between a morbidly obese (body mass index ≥40 kg/m One hundred seventeen morbidly obese patients were compared with 94 normal weight patients. Operative time, length of stay, complications, 30-day readmission, and readmission length were compared. Morbid obesity conveyed no significant increase in 30-day readmission. Operative time was increased at 100 minutes in the morbidly obese group, compared with 90.5 minutes (P = .026). Morbid obesity conveyed no increased risk of length of stay or readmission in this cohort.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.ARTH.2013.10.016
Abstract: In an attempt to preserve proximal femoral bone stock and achieve a better fit in smaller femora, especially in the Asian population, several new shorter stem designs have become available. We investigated the torque to periprosthetic femoral fracture of the Exeter short stem compared with the conventional length Exeter stem in a Sawbone model. Forty-two stems 21 shorter and 21 conventional stems both with three different offsets were cemented in a composite Sawbone model and torqued to fracture. Results showed that Sawbone femurs break at a statistically significantly lower torque to failure with a shorter compared to conventional-length Exeter stem of the same offset. Both standard and short-stem designs are safe to use as the torque to failure is 7-10 times that seen in activities of daily living.
Publisher: Begell House
Date: 2003
DOI: 10.1615/JLONGTERMEFFMEDIMPLANTS.V13.I5.50
Abstract: Patients (n = 81) undergoing total hip replacement (THR) were randomized to receive either standard of care plus fibrin sealant (FS) (10 mL total) or standard of care alone to evaluate the efficacy of FS for reducing blood loss in THR. Considering the 81 intent-to-treat patients, adjusted perioperative blood loss was reduced significantly in the FS group, by 197 mL [95% CI: 45 mL, 319 mL] or 23.5% [95% CI: 5.4%, 38.1%] (p = 0.014). When protocol violators were eliminated, leaving 73 patients, the adjusted FS group perioperative bleeding was reduced by 221 mL [95% CI: 63 mL, 351 mL] or 27.1% [95% CI: 7.6%, 42.5%] (p = 0.0098).
Publisher: Wiley
Date: 30-09-2014
DOI: 10.1002/JBM.A.34954
Abstract: Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the β-tricalcium phosphate (β-TCP) stimulated osteogenesis. It was found that osteocytes responded to the β-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of β-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials.
Publisher: Wiley
Date: 10-11-2017
DOI: 10.1002/JCB.25758
Abstract: Osteoarthritis (OA) is a progressive, age-related disease characterized by the degradation of the cartilage, abnormal bone remodeling, and joint pain eventually leading to disability. The occurrence of clinically diagnosed OA and the incidence of disability show geographic variations, which suggests that lifestyle and factors such as diet play a vital role in the formation and progression of OA. Obesity is associated with a state of low-grade inflammation and increased plasma concentrations of fatty acids such as the saturated fatty acids (SFA). Importantly, obesity is a major risk factor for the development of OA in both weight-bearing and non-weight-bearing joints. Further, obese in iduals bear the full brunt of OA which poses a huge health, social and economic problem, and hence it is essential to increase our understanding of OA and obesity to improve patient care and decrease disease progression. Hence, the current state of knowledge on the relationship between obesity and OA is reviewed, especially the influence of different diets. In particular, we emphasize the role and mechanisms of SFA to cause or worsen OA. J. Cell. Biochem. 118: 453-463, 2017. © 2016 Wiley Periodicals, Inc.
Publisher: SAGE Publications
Date: 02-2007
Abstract: Clinical experience shows that removal of the Exeter long-stem femoral component (220 mm, 240 mm, 260 mm) of total hip arthroplasty is extremely difficult, often requiring splitting of the femur. To identify the reason for this, measurements of stem geometry and force required to pull the stems out of the cement mantle were conducted on three original Exeter long-stem and one standard femoral components. All implants required an initial force of approximately 4 kN for release from the cement. The long-stem components then required much larger forces and hence much higher expenditure of energy to pull them clear of the cement. This was attributed to the reverse taper seen on the nominally cylindrical distal section of the long-stem components. Following re-design of the manufacturing process to ensure the taper continued to the implant's distal tip, four further implants were tested. These demonstrated the requirement for initial cement release but then required no further energy expenditure similar to the standard stem. This study clearly demonstrated that the original difficulty in removing these long stems was owing to the manufacturing process resulting in a reverse taper on the distal stem. The adoption of recommended manufacturing changes to ensure the taper continues to the distal tip removed this difficulty.
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.BIOMATERIALS.2013.11.014
Abstract: Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used β-tricalcium phosphate (β-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to β-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the β-TCP stimulation, indicating that macrophage may participate in the β-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned β-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.
Publisher: Springer International Publishing
Date: 2015
Publisher: Trans Tech Publications Ltd.
Date: 09-02-2008
Publisher: Wiley
Date: 29-04-2010
DOI: 10.1002/ART.27397
Abstract: Previous studies have shown the influence of subchondral bone osteoblasts (SBOs) on phenotypical changes of articular cartilage chondrocytes (ACCs) during the development of osteoarthritis (OA). The molecular mechanisms involved during this process remain elusive, in particular, the signal transduction pathways. The aim of this study was to investigate the in vitro effects of OA SBOs on the phenotypical changes in normal ACCs and to unveil the potential involvement of MAPK signaling pathways during this process. Normal and arthritic cartilage and bone s les were collected for isolation of ACCs and SBOs. Direct and indirect coculture models were applied to study chondrocyte hypertrophy under the influence of OA SBOs. MAPKs in the regulation of the cell-cell interactions were monitored by phosphorylated antibodies and relevant inhibitors. OA SBOs led to increased hypertrophic gene expression and matrix calcification in ACCs by means of both direct and indirect cell-cell interactions. In this study, we demonstrated for the first time that OA SBOs suppressed p38 phosphorylation and induced ERK-1/2 signal phosphorylation in cocultured ACCs. The ERK-1/2 pathway inhibitor PD98059 significantly attenuated the hypertrophic changes induced by conditioned medium from OA SBOs, and the p38 inhibitor SB203580 resulted in the up-regulation of hypertrophic genes in ACCs. The findings of this study suggest that the pathologic interaction of OA SBOs and ACCs is mediated via the activation of ERK-1/2 phosphorylation and deactivation of p38 phosphorylation, resulting in hypertrophic differentiation of ACCs.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/03008200701692354
Abstract: This article investigates in vitro the hypothesis that the frequency profile of ultrasound reflections may be used to characterize degradation and osteoarthritic progression in articular cartilage, irrespective of the effects of transducer orientation. To this end, ultrasound echoes were taken in the time domain from the articular surface and osteochondral junction of normal, collagen meshwork-disrupted, proteoglycan-depleted, and osteoarthritic s les, converted to the frequency domain by fast Fourier transform and analyzed. Our results show the significant effects of specific enzymatic degradation programs on the ultrasound frequency profile of reflections from the cartilage surface and osteochondral junction, and their manifestation in the tissue surrounding a focal osteoarthritic defect. Collagen meshwork disruption was most apparent in the profile of reflections from the articular surface, while proteoglycan depletion was most clearly observed in the reflections from the osteochondral junction. The reflected signals from the osteochondral junction may further contain information about the subchondral bone. From these results we proposed that the analysis of specific frequencies of reflected ultrasound signals has the potential to differentiate normal from degraded articular cartilage-on-bone, when the angle of incidence can be controlled within a +/-1.2 degrees limit. This encourages further research into the effects of progressive artificial degradation of the cartilage matrix and subchondral bone on the spectral profile to quantify the relationship between the frequency profile and the level of specific degradation in naturally degraded joints.
Publisher: Wiley
Date: 11-1998
DOI: 10.1046/J.1365-2559.1998.00546.X
Abstract: Hip joint disease associated with progressive amyloid deposition in uraemic patients receiving chronic haemodialysis treatment often requires treatment by joint arthroplasty. The aim of this study was to determine whether beta 2-microglobulin amyloid deposition occurred in the periprosthetic tissues of arthroplasties that had undergone aseptic loosening and required a revision procedure. Sections of the pseudocapsule, acetabular and femoral pseudomembrane surrounding failed total hip replacements of five uraemic patients known to have beta 2-microglobulin amyloid deposits at the time of primary joint replacement were examined for the presence of beta 2-microglobulin amyloid deposition by Congo red staining and immunohistochemical staining for beta 2-microglobulin and other amyloid proteins. Clinical and radiological features of each case, including postoperative history and extent of osteolysis, were also noted. In all cases evidence of beta 2-microglobulin amyloid deposits were found in one or more of the above periprosthetic tissues. In three of these cases amyloid deposition was extensive. This study shows that beta 2-microglobulin amyloid deposition occurs in revision arthroplasty tissues. Accelerated loosening of the prosthesis is known to occur in uraemic patients and it is possible that beta 2-microglobulin amyloid deposition may contribute to early arthroplasty failure in uraemic patients who remain on haemodialysis treatment.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.ARTH.2013.04.039
Abstract: This study evaluated the energy cost of walking (Cw) with knee flexion contractures (FC) simulated with a knee brace, in total knee arthroplasty (TKA) recipients (n=16) and normal controls (n=15), and compared it to baseline (no brace). There was no significant difference in Cw between the groups at baseline but TKA recipients walked slower (P=0.048) and with greater knee flexion in this condition (P=0.003). Simulated FC significantly increased Cw in both groups (TKA P=0.020, control P=0.002) and this occurred when FC exceeded 20° in the TKA group and 15° in the controls. Reported perceived exertion was only significantly increased by FC in the control group (control P<0.001, TKA P=0.058). Simulated knee FCs less than 20° do not increase Cw or perceived exertion in TKA recipients.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.ARTH.2011.07.015
Abstract: The incidence of pseudotumor formation has been reported to be 1% in patients with metal-on-metal resurfacing arthroplasties. This complication is not exclusive to these patients. We report a case of pseudotumor formation secondary to femoral head-neck corrosion after a metal-on-polyethylene uncemented total hip arthroplasty.
Publisher: IOP Publishing
Date: 28-08-2009
DOI: 10.1088/0031-9155/54/18/015
Abstract: A non-destructive, diffuse reflectance near infrared spectroscopy (DR-NIRS) approach is considered as a potential tool for determining the component-level structural properties of articular cartilage. To this end, DR-NIRS was applied in vitro to detect structural changes, using principal component analysis as the statistical basis for characterization. The results show that this technique, particularly with first-derivative pretreatment, can distinguish normal, intact cartilage from enzymatically digested cartilage. Further, this paper establishes that the use of DR-NIRS enables the probing of the full depth of the uncalcified cartilage matrix, potentially allowing the assessment of degenerative changes in joint tissue, independent of the site of initiation of the osteoarthritic process.
Publisher: Elsevier BV
Date: 10-1998
Publisher: IEEE
Date: 11-2017
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.ARTH.2012.06.001
Abstract: Bleeding-related wound complications cause significant morbidity in lower limb arthroplasty surgery. Patients who require therapeutic anticoagulation in the perioperative period are potentially at higher risk for these complications. This is a retrospective case-control study reviewing all primary total hip arthroplasties performed in a single center during a 5-year period and comparing outcomes of the patients on warfarin with a double-matched control group of patients not on warfarin. The warfarin group had a significantly higher risk of deep joint infection (9% vs 2.2%), hematoma/wound ooze (28% vs 4%), and superficial infection (13.5% vs 2.2%). Managing patients undergoing total hip arthroplasty with therapeutic anticoagulation is a balance between the risk of thromboembolic disease and bleeding-related complications. Improved understanding of this risk will better allow patients to make an informed decision regarding their elective arthroplasty surgery.
Publisher: Mary Ann Liebert Inc
Date: 04-2007
Abstract: The demand for treatment strategies for damaged musculoskeletal tissue is continuously growing, especially with the increasing number of older people with degenerative diseases of the skeletal system such as osteoarthritis (OA). Because depletion of multipotent cells has been implicated in degenerative joint diseases, cell-based therapies have been proposed for tissue regeneration, especially for cartilage repair. The aim of the present study is to focus on the possibility of deriving and expanding multipotential mesenchymal stem cells (MSCs) from bone marrow s les of patients with OA by characterizing MSCs at the single cell level. Single-cell clonal cultures were established in 96-well plates by limiting dilution of bone marrow stromal cells (BMSCs) from three patients with OA. Fourteen clones were established for subsequent characterization. There was a wide variation in cell doubling times, with the time taken to reach 20 population doublings ranging from 37 days to more than 100 days. The clones were grouped into fast-growing and slow-growing clones. All except one of the fast-growing stem cell clones were tripotential. However, the slow-growing clones showed limited differentiation potential and morphological changes associated with cellular senescence with extended duration in culture. Flow cytometric analysis indicated a strong need to investigate for novel cell-surface characteristic markers of BMSCs because there was no obvious difference in the expression of the selected characteristic BMSC cell surface markers CD29, CD44, CD90, CD105, and CD166 between fast-growing and slow-growing clones. This study has demonstrated the existence of a fast-growing multipotential MSC population from bone marrow s les of patients with OA. Therefore, despite a supposedly smaller stem cell compartment in these patients, we demonstrate here that they can still yield a potentially therapeutically useful source of syngeneic MSCs.
Publisher: Elsevier BV
Date: 10-2007
DOI: 10.1016/J.ARTH.2007.03.012
Abstract: The effect of cyclic loading on the torsional stiffness of a polished double-tapered femoral stem was investigated in vitro. Initial torsional stability was compared with torsional stability after cyclic loading. Stems were removed from the cement mantle and reinserted without the use of additional cement. Torsional stability was measured after reinsertion and after further cyclic loading. Subsidence of the stem was observed. No difference in torsional stiffness was observed during loading. No difference between the stiffness before extraction and after reinsertion was observed. Torsional stiffness of an Exeter stem does not decrease after axial subsidence under cyclic loading. Stability is retained after reinsertion into the original cement mantle. Debonding of the Exeter stem is not associated with rotational instability of the implant.
Publisher: Public Library of Science (PLoS)
Date: 24-02-2016
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BIOMATERIALS.2014.01.062
Abstract: The development of effective therapeutic strategies against prostate cancer bone metastases has been impeded by the lack of adequate animal models that are able to recapitulate the biology of the disease in humans. Bioengineered approaches allow researchers to create sophisticated experimentally and physiologically relevant in vivo models to study interactions between cancer cells and their microenvironment under reproducible conditions. The aim of this study was to engineer a morphologically and functionally intact humanized organ bone which can serve as a homing site for human prostate cancer cells. Transplantation of biodegradable tubular composite scaffolds seeded with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone construct including a large number of human mesenchymal cells which were shown to be metabolically active and capable of producing extracellular matrix components. Micro-CT analysis demonstrated that the newly formed ossicle recapitulated the morphological features of a physiological organ bone with a trabecular network surrounded by a cortex-like outer structure. This microenvironment was supportive of the lodgement and maintenance of murine haematopoietic cell clusters, thus mimicking a functional organ bone. Bioluminescence imaging demonstrated that luciferase-transduced human PC3 cells reproducibly homed to the humanized tissue engineered bone constructs, proliferated, and developed macro-metastases. This model allows the analysis of interactions between human prostate cancer cells and a functional humanized bone organ within an immuno-incompetent murine host. The system can serve as a reproducible platform to study effects of therapeutics against prostate cancer bone metastases within a humanized microenvironment.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.ARTH.2011.05.025
Abstract: Postoperative fever in arthroplasty patients is common. The value of diagnostic workup of fever in this instance is of questionable utility. Studies have shown that blood cultures in this scenario add little to clinical management, but s le sizes have been small and the use of blood cultures in this setting continues. This study aimed to examine the value of blood cultures in the assessment of postoperative fever in a large arthroplasty population. The medical records of 101 patients who had 141 blood culture sets taken during a 2-year period were retrospectively analyzed. Of the 141 blood culture sets, only 2 returned positive results. These were both thought to be as a result of skin contamination at the time of venipuncture. No infectious sequelae occurred in either patient. We conclude that blood cultures have no role to play in the assessment of the febrile, otherwise asymptomatic arthroplasty patient in the early postoperative period.
Publisher: Hindawi Limited
Date: 05-10-2015
DOI: 10.1002/TERM.1619
Abstract: The interaction between host and donor cells is believed to play an important role in osteogenesis. However, it is still unclear how donor osteogenic cells behave and interact with host cells in vivo. The purpose of this study was to track the interactions between transplanted osteogenic cells and host cells during osteogenesis. In vitro migration assay was carried out to investigate the ability of osteogenic differentiated human mesenchymal stem cells (O-hMSCs) to recruit MSCs. At the in vivo level, O-hMSCs were implanted subcutaneously or into skull defects in severe combined immunodeficient (SCID) mice. New bone formation was observed by micro-CT and histological procedures. In situ hybridization (ISH) against human Alu sequences was performed to distinguish donor osteogenic cells from host cells. In vitro migration assay revealed an increased migration potential of MSCs by co-culturing with O-hMSCs. In agreement with the results of in vitro studies, ISH against human Alu sequences showed that host mouse MSCs migrated in large numbers into the transplantation site in response to O-hMSCs. Interestingly, host cells recruited by O-hMSCs were the major cell populations in newly formed bone tissues, indicating that O-hMSCs can trigger and initiate osteogenesis when transplanted in orthotopic sites. The observations from this study demonstrated that in vitro induced O-hMSCs were able to attract host MSCs in vivo and were involved in osteogenesis together with host cells, which may be of importance for bone tissue-engineering applications.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.ARTH.2010.03.014
Abstract: The use of the cement-in-cement technique for femoral component revisions has been well described. The application of this technique in the management of selected Vancouver B2 periprosthetic femur fractures, after careful preoperative and intraoperative evaluation, offers a novel alternative that is rapid and technically less demanding, with resulting decreased blood loss and decreased risk of iatrogenic fragmentation of bone during cement removal.
Publisher: Elsevier BV
Date: 09-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: Informa UK Limited
Date: 16-01-2021
Publisher: Mary Ann Liebert Inc
Date: 12-2014
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.BONE.2009.10.014
Abstract: Osteoarthritic subchondral bone is characterized by abnormal bone density and enhanced production of bone turnover markers, an indication of osteoblast dysfunction. Several studies have proposed that pathological changes in articular cartilage influence the subchondral bone changes, which are typical of the progression of osteoarthritis however, direct evidence of this has yet to be reported. The aim of the present study was to investigate what effects articular cartilage cells, isolated from normal and osteoarthritic joints, may have on the subchondral bone osteoblast phenotype, and also the potential involvement of the mitogen activated protein kinase (MAPK) signalling pathway during this process. Our results suggest that chondrocytes isolated from a normal joint inhibited osteoblast differentiation, whereas chondrocytes isolated from an osteoarthritic joint enhanced osteoblast differentiation, both via a direct and indirect cell interaction mechanisms. Furthermore, the interaction of subchondral bone osteoblasts with osteoarthritic chondrocyte conditioned media appeared to significantly activate ERK1/2 phosphorylation. On the other hand, conditioned media from normal articular chondrocytes did not affect ERK1/2 phosphorylation. Inhibition of the MAPK-ERK1/2 pathways reversed the phenotype changes of subchondral bone osteoblast, which would otherwise be induced by the conditioned media from osteoarthritic chondrocytes. In conclusion, our findings provide evidence that osteoarthritic chondrocytes affect subchondral bone osteoblast metabolism via an ERK1/2 dependent pathway.
Publisher: Elsevier BV
Date: 04-2007
Publisher: Springer Science and Business Media LLC
Date: 02-2010
Publisher: Trans Tech Publications Ltd.
Date: 09-02-2008
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.ACTBIO.2012.05.008
Abstract: Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca(2+) (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca(2+) signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca(2+) pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca(2+) pathways during osteogenic differentiation on modified titanium implant surfaces.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.CLINBIOMECH.2008.06.007
Abstract: A microscopic layer of surface active phospholipids overlays the articular cartilage of the knee. Its depletion in osteoarthritic joints results in loss of lubrication and load-bearing efficiency. We hypothesize that exposure of articular cartilage to the dominant unsaturated phospholipid component of knee surfactant can regenerate the load-bearing properties of the tissue. This was evaluated by studying the stress-strain and stiffness characteristics of normal intact and lipid-depleted cartilage exposed to lipid-based surfactants for known durations. Normal intact, lipid-depleted and surfactant-treated bovine articular cartilage specimens were compressed at 0.5mm/min to a maximum strain of 40% and their stress-strain and stiffness data were compared. The stiffness of lipid-depleted s les increased by 40% on average relative to the normal after exposure of the same s les to saturated surfactant for one and 24h, the average stiffness decreased by 25% and 62%, respectively from this high value. On the other hand, exposure of delipidized specimens to a mixture of selected unsaturated surfactant species for one and 24h resulted in a reduction of 85% and 90% in the stiffness of the depilidized s les respectively, largely reversing the effect of lipid removal to a level much closer to that of the normal intact cartilage and therefore better than that obtained with incubation in the saturated surfactant. Lipid loss in articular cartilage results in a consistent increase in stiffness relative to normal tissue stiffness. This consequence of lipid loss can be partially reversed by the reintroduction of surface active phospholipids. The results of this study show that the lipid components of cartilage play an important role in determining the compliance of the loaded tissue.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.JOCA.2012.07.007
Abstract: The aim of this study was to demonstrate the potential of near-infrared (NIR) spectroscopy for categorizing cartilage degeneration induced in animal models. Three models of osteoarthritic degeneration were induced in laboratory rats via one of the following methods: (1) menisectomy (MSX) (2) anterior cruciate ligament transection (ACLT) and (3) intra-articular injection of mono-ido-acetate (1 mg) (MIA), in the right knee joint, with 12 rats per model group. After 8 weeks, the animals were sacrificed and tibial knee joints were collected. A custom-made near-infrared (NIR) probe of diameter 5 mm was placed on the cartilage surface and spectral data were acquired from each specimen in the wave number range 4,000-12,500 cm(-1). Following spectral data acquisition, the specimens were fixed and Safranin-O staining was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis based on principal component analysis and partial least squares regression, the spectral data were then related to the Mankin scores of the s les tested. Mild to severe degenerative cartilage changes were observed in the subject animals. The ACLT models showed mild cartilage degeneration, MSX models moderate, and MIA severe cartilage degenerative changes both morphologically and histologically. Our result demonstrates that NIR spectroscopic information is capable of separating the cartilage s les into different groups relative to the severity of degeneration, with NIR correlating significantly with their Mankin score (R(2) = 88.85%). We conclude that NIR is a viable tool for evaluating articular cartilage health and physical properties such as change in thickness with degeneration.
Publisher: Wiley
Date: 27-01-2017
DOI: 10.1002/ACR.23117
Abstract: To evaluate the long-term benefit of providing a post-acute, outpatient group exercise program for patients following primary total knee replacement (TKR) surgery for osteoarthritis. A multicenter randomized clinical trial was conducted in 12 Australian public and private hospital centers. A total of 422 participants, ages 45-75 years, were randomly allocated prior to hospital discharge to the post-acute group exercise program or to usual care and were assessed at 6 weeks, 6 months, and 12 months after surgery. The main outcomes were operated knee pain and activity limitations at 12 months using the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire. Secondary outcomes included health-related quality of life (Short Form 12 health survey), knee extension and flexion strength, stair-climb power, 50-foot walk speed, and active knee range of motion. While both allocation groups achieved significant improvements in knee pain and activity limitations over the 12-month followup period, there were no significant differences in these main outcomes, or in the secondary physical performance measures, between the 2 treatment allocations. Twelve months after TKR, 69% and 72% of participants allocated to post-acute exercise and usual acute care, respectively, were considered to be treatment-responders. While population normative values for self-report measures of pain, activity limitation, and health-related quality of life were attained 12 months after TKR, marked deficits in physical performance measures remained. Providing access to a post-acute group exercise program did not result in greater reductions in long-term knee pain or activity limitations than usual care. Patients undergoing primary TKR retain marked physical performance deficits 12 months after surgery.
Publisher: SAGE Publications
Date: 23-10-2014
Abstract: Metal ion release is common following total hip arthroplasty, yet postoperative levels have not been defined for most stems currently used in clinical practice. To assess metal ion release in the serum of patients with well functioning unilateral Exeter V40 primary total hip arthroplasties one year after surgery. Whole blood chromium and serum cobalt levels were measured in 20 patients following primary total hip arthroplasty with the Exeter V40 stem and a variety of acetabular components one year after surgery. Whole blood chromium levels were within the normal range (10-100 nmol/L), with a single mild elevation of serum cobalt (normal ≤20 nmol/L). In well functioning primary unilateral total hip arthroplasty using the Exeter V40 stem with a variety of acetabular components one year post surgery, whole blood chromium levels are normal and serum cobalt elevations are rare and mild.
Publisher: The Royal Society
Date: 10-2023
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.ARTH.2008.01.130
Abstract: A randomized controlled trial was performed to assess the effect of a rim cutter device on cement mantles in modern elective total hip arthroplasty using a flanged acetabular component. Forty patients were randomized to a rim cutter (21) or control (19) group. A statistically significant improvement in cement penetration was demonstrated in zone 1 (10.1 vs 8.6 mm, P = .023), and in cement mantle thickness in zones 2 and 3 (7.8 and 6.7 mm vs 5.7 and 5.4 mm [P < .001 and P = .017]), with a reduced incidence of bottoming out of the socket (1/21 vs 8/19 [P = .007]). Cement mantle thicknesses greater than 8 mm were achieved more consistently in the rim cutter group (30% vs 2%). This technique improves cement penetration and mantle thickness in a reliable manner.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 15-05-2021
Publisher: Wiley
Date: 20-07-2010
DOI: 10.1002/JBM.A.32873
Abstract: Microsphere systems with the ideal properties for bone regeneration need to be bioactive, and at the same time possess the capacity for controlled protein/drug-delivery however, the current crop of microsphere system fails to fulfill these properties. The aim of this study was to develop a novel protein-delivery system of bioactive mesoporous glass (MBG) microspheres by a biomimetic method through controlling the density of apatite on the surface of microspheres, for potential bone tissue regeneration. MBG microspheres were prepared by using the method of alginate cross-linking with Ca(2+) ions. The cellular bioactivity of MBG microspheres was evaluated by investigating the proliferation and attachment of bone marrow stromal cell (BMSC). The loading efficiency (LE) and release kinetics of bovine serum albumin (BSA) on MBG microspheres were investigated after coprecipitating with biomimetic apatite in simulated body fluids (SBF). The results showed that MBG microspheres supported BMSC attachment and the Si-containing ionic products from MBG microspheres stimulated BMSCs proliferation. The density of apatite on MBG microspheres increased with the length of soaking time in SBF. BSA-LE of MBG was significantly enhanced by coprecipitating with apatite. Furthermore, the LE and release kinetics of BSA could be controlled by controlling the density of apatite formed on MBG microspheres. Our results suggest that MBG microspheres are a promising protein-delivery system as a filling material for bone defect healing and regeneration.
Publisher: Springer Science and Business Media LLC
Date: 2013
DOI: 10.1186/AR4333
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2005
DOI: 10.1097/01.BLO.0000149994.58542.C9
Abstract: We investigated the effect of pneumatic pressure applied to the proximal musculature of the sheep foreleg on load at the site of a transverse osteotomy of the distal radius. The distal radii of 10 fresh sheep foreleg specimens were osteotomized and a pressure sensor was inserted between the two bone fragments. An inflatable cuff, connected to a second pressure sensor, was positioned around the proximal forelimb musculature and the leg then was immobilized in a plaster cast. The inflatable cuff was inflated and deflated repeatedly to various pressures. Measurements of the cuff pressure and corresponding change in pressure at the osteotomy site were recorded. The results indicated that application of pneumatic pressure to the proximal foreleg musculature produced a corresponding increase in load at the osteotomy site. For the cuff pressures tested (109.8-238.4 mm Hg), there was a linear correlation with the load at the osteotomy site with a gradient of 12 mm Hg/N. It is conceivable, based on the results of this study, that a technique could be developed to provide dynamic loading to accelerate fracture healing in the upper limb of humans.
Publisher: Springer Science and Business Media LLC
Date: 23-08-2007
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.ARTHRO.2014.04.097
Abstract: The purpose of this study was to demonstrate the potential of near infrared (NIR) spectroscopy for characterizing the health and degenerative state of articular cartilage based on the components of the Mankin score. Three models of osteoarthritic degeneration induced in laboratory rats by anterior cruciate ligament (ACL) transection, meniscectomy (MSX), and intra-articular injection of monoiodoacetate (1 mg) (MIA) were used in this study. Degeneration was induced in the right knee joint each model group consisted of 12 rats (N = 36). After 8 weeks, the animals were euthanized and knee joints were collected. A custom-made diffuse reflectance NIR probe of 5-mm diameter was placed on the tibial and femoral surfaces, and spectral data were acquired from each specimen in the wave number range of 4,000 to 12,500 cm(-1). After spectral data acquisition, the specimens were fixed and safranin O staining (SOS) was performed to assess disease severity based on the Mankin scoring system. Using multivariate statistical analysis, with spectral preprocessing and wavelength selection technique, the spectral data were then correlated to the structural integrity (SI), cellularity (CEL), and matrix staining (SOS) components of the Mankin score for all the s les tested. ACL models showed mild cartilage degeneration, MSX models had moderate degeneration, and MIA models showed severe cartilage degenerative changes both morphologically and histologically. Our results reveal significant linear correlations between the NIR absorption spectra and SI (R(2) = 94.78%), CEL (R(2) = 88.03%), and SOS (R(2) = 96.39%) parameters of all s les in the models. In addition, clustering of the s les according to their level of degeneration, with respect to the Mankin components, was also observed. NIR spectroscopic probing of articular cartilage can potentially provide critical information about the health of articular cartilage matrix in early and advanced stages of osteoarthritis (OA). This rapid nondestructive method can facilitate clinical appraisal of articular cartilage integrity during arthroscopic surgery.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.ARTH.2012.08.016
Abstract: The aim of this study was to perform a biomechanical analysis of the cement-in-cement (c-in-c) technique for fixation of selected Vancouver Type B1 femoral periprosthetic fractures and to assess the degree of cement interposition at the fracture site. Six embalmed cadaveric femora were implanted with a cemented femoral stem. Vancouver Type B1 fractures were created by applying a combined axial and rotational load to failure. The femora were repaired using the c-in-c technique and reloaded to failure. The mean primary fracture torque was 117 Nm (SD 16.6, range 89-133). The mean revision fracture torque was 50 Nm (SD 16.6, range 29-74), which is above the torque previously observed for activities of daily living. Cement interposition at the fracture site was found to be minimal.
Publisher: Informa UK Limited
Date: 2004
DOI: 10.1080/03008200490442653
Abstract: In alignment with the proposition that a lipid layer overlays the superficial zone of the articular cartilage, this study presents the consequence of the removal of lipids on the load-bearing characteristics of the tissue. Both normal unmodified and delipidized cartilage matrices were loaded at four different strain-rates of 1.3 x 10(-4)/s, 1.3 x 10(-3)/s, 1.3 x 10(-2)/s, and 1.3 x 10(-1)/s to strains of no more than 40%, to compare their stress-strain and stiffness-strain-rate characteristics. Our results demonstrate that at the lowest strain-rate of 1.3 x 10(-4)/s, the stiffness of the delipidized matrix was lower in comparison to that of the normal unmodified tissue. This response was reversed at higher strain-rates of 1.3 x 10(-2)/s and above. We conclude, therefore, that in general, at physiological rates of loading, the depletion of lipids from the articular cartilage reduces its compliance by at least 25%. We infer from the present study that this degenerative stiffening is an important contributing factor in impairing the tissue's load processing function in osteoarthritic joints.
Publisher: Elsevier BV
Date: 08-1999
Publisher: Hindawi Limited
Date: 22-03-2018
DOI: 10.1002/TERM.2327
Abstract: Cell-cell interaction is believed to play a critical role in the cell-based therapy for bone regeneration. However, the mechanisms involved in the interaction between donor cells and host cells during the bone healing process are still not clear. This study investigated the potential effect of vascular endothelial growth factor A (VEGFA) produced by osteogenically differentiated mesenchymal stem cells (O-MSCs) on the recruitment and regulation of undifferentiated MSCs and macrophages during osteogenesis. Factors secreted from MSCs during osteogenic differentiation were monitored by cytokine arrays. Indirect coculture models were applied to study the effect of VEGFA derived from O-MSCs on the motility, cell morphology and CXCL12/CXCR4 expression in MSCs as well as the regulation of local immune response. A mouse skull defect model was used to unveil the cell recruitment, macrophage activity and new bone formation following O-MSCs transplantation. It was found that VEGFA secretion increased dramatically during the osteogenic differentiation of MSCs. The secreted VEGFA by O-MSCs stimulated the expression of CXCL12/CXCR4, resulting in the recruitment of MSCs and macrophages to the bone defects. It was noted that O-MSCs could regulate the local inflammation by modulating the expression of proinflammatory cytokines in macrophages and neutralizing VEGFA produced by O-MSCs resulted in significant decrease of cell recruitment, cytokine secretion and new bone formation. This study demonstrates that VEGFA secreted by O-MSCs plays a pivotal role in the cell recruitment and regulation of local immune response during osteogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/03008200701458749
Abstract: In view of the controversy of the clinical use of hyperbaric oxygen (HBO) treatment to stimulate fracture healing and bone regeneration, we have analyzed the effects of daily exposure to HBO on the proliferation and differentiation of human osteoblasts in vitro. HBO stimulated proliferation when osteoblasts were cultured in 10% fetal calf serum (FCS), whereas an inhibitory effect of HBO was observed when cultures were supplemented with 2% FCS. On the other hand, HBO enhanced biomineralization with an increase in bone nodule formation, calcium deposition, and alkaline phosphatase activity, whereas no cytotoxic effect was detected using a lactate dehydrogenase activity assay. The data suggest that the exposure of osteoblasts to HBO enhances differentiation toward the osteogenic phenotype, providing cellular evidence of the potential application of HBO in fracture healing and bone regeneration.
Publisher: Elsevier BV
Date: 02-2023
Publisher: Springer Science and Business Media LLC
Date: 27-10-2014
DOI: 10.1007/S00402-009-0819-7
Abstract: Whilst intramedullary nailing is a commonly accepted technique for lower limb fracture fixation, the cost of nails can be prohibitive in hospitals in developing nations. In these institutions bone cement has found many off label applications, that whilst are effective do not meet manufacturers guidelines. The aim of this study was to examine the biomechanics of one such application, fracture fixation using a bone cement intramedullary nail. Five porcine femurs underwent a mid-shaft osteotomy and were fixed using a nail made from antibiotic simplex bone cement. The torsional and flexural stiffness and shear modulus of these constructs were compared to five intact porcine femurs. The bone cement intramedullary nail was able to achieve relative stability in both torsion, with a mean shear modulus of 0.17 GPa and in flexion with a mean flexural stiffness of 358 N/mm. This corresponds to 47 and 22% of the respective measurements in the intact femurs. The mean ultimate flexural strength of fracture/nail constructs was 936 +/- 350 N, which is 20% of the ultimate flexural strength of an intact porcine femur (4,820 +/- 698 N). Intramedullary nails made from bone cement were able to provide sufficient promise in this situation to warrant further investigation for their applicability as a low cost alternative for use in developing countries.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.ARTH.2014.04.022
Abstract: Mortality following hip arthroplasty is affected by a large number of confounding variables each of which must be considered to enable valid interpretation. Relevant variables available from the 2011 NJR data set were included in the Cox model. Mortality rates in hip arthroplasty patients were lower than in the age-matched population across all hip types. Age at surgery, ASA grade, diagnosis, gender, provider type, hip type and lead surgeon grade all had a significant effect on mortality. Schemper's statistic showed that only 18.98% of the variation in mortality was explained by the variables available in the NJR data set. It is inappropriate to use NJR data to study an outcome affected by a multitude of confounding variables when these cannot be adequately accounted for in the available data set.
Publisher: Wiley
Date: 23-06-2010
DOI: 10.1111/J.1445-2197.2010.05346.X
Abstract: The objective of routine outpatient assessment of well-functioning patients after primary total hip arthroplasty (THA) is to detect asymptomatic failure of prostheses to guide recommendations for early intervention. We have observed that the revision of THAs in asymptomatic patients is highly uncommon. We therefore question the need for routine follow-up of patients after THA. A prospective analysis of an orthopaedic database identified 158 patients who received 177 revision THAs over a four-year period. A retrospective chart review was conducted. Patient demographics, primary and revision surgery parameters and follow-up information were recorded and cross-referenced with Australian Orthopaedic Association National Joint Replacement Registry data. One hundred ten THAs in 104 patients (average age 70.4 (SD 9.8 years)). There were 70 (63.6%) in total, 13 (11.8%) femoral and 27 (24.5%) acetabular revisions. The indications for revision were aseptic loosening (70%), dislocation (8.2%), peri-prosthetic fracture (7.3%), osteolysis (6.4%) and infection (4.5%). Only four (3.6%) were asymptomatic revisions. A mean of 5.3 (SD 5.2 and 1.9 (SD 5.3)) follow-up appointments were required before revision in patients with and without symptoms, respectively. The average time from the primary to revision surgery was 11.8 (SD 7.23) years. We conclude that patients with prostheses with excellent long-term clinical results as validated by joint registries, routine follow-up of asymptomatic THA should be questioned and requires further investigation. Based on the work of this study, the current practice of routine follow-up of asymptomatic THA may be excessively costly and unnecessary, and a less resource-intensive review method may be more appropriate.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Mary Ann Liebert Inc
Date: 04-2008
Abstract: Osteophytes are a distinct feature of osteoarthritis (OA). Their formation may be related to pluripotential cells in the periosteum responding to stimulus during OA. This study aimed to isolate stem cells from osteophyte tissues and to characterize their phenotype, proliferation, and differentiation potential, as well as their immunomodulatory properties. Osteophyte-derived cells were isolated from osteophyte tissue s les collected during knee replacement surgery. These cells were characterized by the expression of cell-surface antigens, differentiation potential into mesenchymal lineages, growth kinetics, and modulation of alloimmune responses. Multipotential stem cells were identified from all osteophyte s les, namely osteophyte-derived mesenchymal stem cells (oMSCs). The surface antigen expression of oMSCs was consistent with that of MSCs they lacked the hematopoietic and common leukocyte markers (CD34, CD45) while expressing those related to adhesion (CD29, CD166, CD44) and stem cells (CD90, CD105, CD73). The proliferation capacity of oMSCs in culture was superior to that of bone marrow-derived MSCs (bMSCs), and these cells readily differentiated into tissues of the mesenchymal lineages. oMSCs also demonstrated the ability to suppress allogeneic T cell proliferation, which was associated with the expression of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Our results showed that osteophyte-derived cells had similar properties to MSCs in the expression of antigen phenotype, differential potential, and suppression of alloimmune response. Furthermore, when compared to bMSCs, oMSCs maintained a higher proliferative capacity, which may offer new insights of the tissue formation and potentially an alternative source for therapeutic stem cell-based tissue regeneration.
Publisher: Elsevier BV
Date: 2008
DOI: 10.1016/J.BONE.2007.08.048
Abstract: In both physiological and pathological processes, periosteum plays a determinant role in bone formation and fracture healing. However, no specific report is available so far focusing on the detailed structural and major cellular differences between the periostea covering different bone surface in relation to ageing. The aim of this study is to compare the structural and cellular differences in diaphyseal and metaphyseal periostea in different aged rats using histological and immunohistochemical methods. Four female Lewis rats from each group of juvenile (7 weeks old), mature (7 months old) and aged groups (2 years old) were sacrificed and the right femur of each rat was retrieved, fixed, decalcified and embedded. Five-micrometer thick serial sagittal sections were cut and stained with Hematoxylin and Eosin, Stro-1 (stem cell marker), F4/80 (macrophage marker), TRAP (osteoclast marker) and vWF (endothelial cell marker). One-millimeter lengths of middle diaphyseal and metaphyseal periosteum were selected for observation. The thickness, total cell number and positive cell number for each antibody were measured and compared in each periosteal area and different aged groups. The results were subjected to two-way ANOVA and SNK tests. The results showed that the thickness and cell number in diaphyseal periosteum decreased with age (p<0.001). In comparison with diaphyseal area, the thickness and cell number in metaphyseal periosteum were much higher (p 0.05). However, the juvenile rats had more Stro1(+), F4/80(+) cells and blood vessels and fewer TRAP(+) cells in different periosteal areas compared with other groups (p<0.001). The aged rats showed much fewer Stro1(+) cells, but more F4/80(+), TRAP(+) cells and blood vessels in the cambial layer of metaphyseal periosteum (p<0.001). In conclusion, structure and cell population of periosteum appear to be both age-related and site-specific. The metaphyseal periosteum of aged rats seems more destructive than diaphyseal part and other age groups. Macrophages in the periosteum may play a dual important role in osteogenesis and osteoclastogenesis.
Publisher: Wiley
Date: 12-2005
DOI: 10.1111/J.1445-2197.2005.03497.X
Abstract: Internal fixation of fractures using plates and screws is a common method of treatment. Occasionally the internal fixation fails prior to fracture healing. This often requires revision surgery. Determining the force that internal fixation needs to withstand postoperatively would enable this force to be applied intraoperatively as a test to predict successful fixation. The purpose of the present paper was to determine the minimum stripping torque needed to predict successful internal fixation strength. The pull-out strength and stripping torque relationships of 4.5-mm cortical bone screws in Sawbones polyurethane foam were determined. Screw forces were directly measured using an LCM load cell washer on a model intertrochanteric neck of femur fracture fixed with 135 degrees 4-hole pin and plate loaded to single leg stance conditions. Additionally a 135 degrees 4-hole pin and plate was mounted on foam blocks and loaded until failure of the shaft screws from the foam occurred. Predicted stripping torque/yield load was determined. Pull-out strength and stripping torque of 4.5-mm cortical bone screws in polyurethane foam have a high degree of linear correlation R(2) = 0.95. Direct measurement of shaft screw forces at single leg stance conditions were 585-686 N. This correlated with a stripping torque of 0.9 Nm. Load to yield testing at single leg stance conditions corresponded to a stripping torque of 1.8 Nm. Withstanding 0.9-1.8 Nm of torque during insertion of the femoral shaft screws of a 135 degrees 4-hole pin and plate predicts that the construct will successfully withstand single leg stance.
Publisher: SAGE Publications
Date: 12-2009
Abstract: This paper is a sequel to previously published findings showing that mechanical indentation alone cannot clearly discriminate between normal and degraded articular cartilage. Consequently, the structural elasticity potential ℜ c = ɛ r / σ i , which combines indentation stress σ i with near-instantaneous rebound ɛ r following unloading, is hypothesized as a potential cartilage assessment parameter, which arguably measures the integrity of the collagen fibre—proteoglycan entrapment system. To establish the validity of our hypothesis, s les of normal intact, artificially degraded, and osteoarthritic bovine cartilage were subjected to quasi-static compression at 0.1 s −1 and 0.025 s −1 to 30 per cent strain and then unloaded. A significant reduction in recovery was observed for artificially and naturally degraded s les in the first 5 s following unloading ( p .01). The structural elasticity potential provided a considerable improvement over the results obtained using the in idual indentation and rebound parameters to distinguish between paired normal and artificially degraded s les and indicated a high statistical significance of p .005 when applied to the differentiation of normal and osteoarthritic s les.
Publisher: Trans Tech Publications, Ltd.
Date: 09-2010
DOI: 10.4028/WWW.SCIENTIFIC.NET/JBBTE.6.1
Abstract: Polymer microspheres loaded with bioactive particles, biomolecules, proteins, and/or growth factors play important roles in tissue engineering, drug delivery, and cell therapy. The conventional double emulsion method and a new method of electrospraying into liquid nitrogen were used to prepare bovine serum albumin (BAS)-loaded poly(lactic-co-glycolic acid) (PLGA) porous microspheres. The particle size, the surface morphology and the internal porous structure of the microspheres were observed using scanning electron microscopy (SEM). The loading efficiency, the encapsulation efficiency, and the release profile of the BSA-loaded PLGA microspheres were measured and studied. It was shown that the microspheres from double emulsion had smaller particle sizes (3-50 m), a less porous structure, a poor loading efficiency (5.2 %), and a poor encapsulation efficiency (43.5%). However, the microspheres from the electrospraying into liquid nitrogen had larger particle sizes (400-600 m), a highly porous structure, a high loading efficiency (12.2%), and a high encapsulation efficiency (93.8%). Thus the combination of electrospraying with freezing in liquid nitrogen and subsequent freeze drying represented a suitable way to produce polymer microspheres for effective loading and sustained release of proteins.
Publisher: SAGE Publications
Date: 15-04-2009
Abstract: With the aim of providing information for modelling joint and limb systems, widely available constitutive hyperelastic laws are evaluated in this paper for their ability to predict the mechanical responses of normal and osteoarthritic articular cartilage. Load—displacement data from mechanical indentation were obtained for normal and osteoarthritic cartilage at 0.1 s −1 and 0.025 s −1 and converted to the stress—stretch ratio. The data were then fitted to the ArrudA—Boyce, Mooney—Rivlin, neo-Hookean, Ogden, polynomial, and Yeoh hyperelastic laws in the MATLAB environment. Although each of the hyperelastic laws performed satisfactorily at the higher rate of loading, their ability to fit experimental data at the lower loading rate varied considerably. For the preferred models, coefficients were provided for stiff, soft, and average tissues to represent normal and degraded tissue at high and low loading rates. The present authors recommend the use of the Mooney—Rivlin or the Yeoh models for describing both normal and degraded articular cartilage, with the Mooney—Rivlin model providing the best compromise between accuracy and required computational power.
Publisher: Elsevier BV
Date: 04-2008
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.ARTH.2006.06.003
Abstract: The influence of dislocation on functional outcomes of primary total hip arthroplasty is unclear. The purpose of this study was to assess the effect of nonrecurrent dislocations treated with closed reduction after primary total hip arthroplasty on postoperative outcome in the short to medium term. Ninety-six patients were enrolled in this retrospective case-control study. There were 32 patients who had a postoperative dislocation. The control group consisted of 64 matched patients who did not dislocate. All patients had a minimum of 1-year follow-up. The 2 groups were compared using the SF-12, reduced WOMAC, and satisfaction questionnaire. There was no statistical difference between the 2 groups in subjective functional outcomes using the WOMAC or SF-12. However, there was a trend toward better quality of life scores in the control group, and they were more satisfied with their surgery compared with the dislocation group.
Publisher: Wiley
Date: 26-02-2014
DOI: 10.1111/ANS.12552
Abstract: Magnetic resonance imaging (MRI) is being increasingly utilized to define pathology and guide treatment in patients presenting with wrist pain. The clinical relevance of MRI identified or confirmed pathology has not been established, and the prevalence of asymptomatic MRI pathology is not known. Twenty volunteers with no previous wrist injury or symptoms underwent bilateral MRI wrist studies in this exploratory diagnostic study. The scans were reported by an experienced musculoskeletal radiologist and an experienced wrist surgeon, with a consensus reached on each report. There were 3.15 positive MRI findings per wrist. There were 126 positive findings (range 1-6 per wrist). Sixty-eight ganglia were identified. Eleven ligament tears or perforations were also identified. Increased joint fluid was seen at many sites, most frequently adjacent to the piso-triquetral joint. The accuracy of MRI in identifying triangular fibrocartilage complex tears, intercarpal ligament tears and carpal bone osteonecrosis is rapidly being refined. Positive MRI findings are common and may be coincidental in patients with wrist pain. MRI findings need to be correlated closely with clinical examination and history.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2016
DOI: 10.1007/S00109-016-1425-0
Abstract: Osteoarthritis (OA) is a chronic, incurable and destructive joint disease that is characterized by chondrocyte hypertrophy and cartilage degradation. Angiogenesis, mediated by the action of vascular endothelial growth factor (VEGF), is known to be a contributing factor in the pathogenesis of OA. In this study, we use a lentivirus-based approach to investigate whether VEGF knockdown would be beneficial to chondrogenesis and could prevent or slow down OA progression. We first profiled cytokines in human OA cartilage using cytokine antibody arrays. This revealed that as many as 21 angiogenesis-related cytokines were significantly upregulated in severe OA cartilage compared to mild OA s les. Next, we infected chondrocytes with VEGF small hairpin RNA (shRNA) lentivirus (LV-VEGF shRNA) and treated these cells with tumour necrosis factor alpha (TNF-α) to induce hypertrophy. The results showed that inhibition of VEGF not only enhanced chondrogenic differentiation, but also protected chondrocytes from TNF-α-induced hypertrophy. We also found that knockdown of VEGF suppressed TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. Furthermore, using a surgically induced OA rat model, we showed that VEGF inhibition delayed OA progression in animals given intra-articular injection of LV-VEGF shRNA. In conclusion, in this study, we have shown that VEGF knockdown can enhance chondrogenesis and prevent OA progression, thus providing evidence that inhibition of VEGF may be a potential therapeutic approach for OA patients. Numerous pro-angiogenic factors are upregulated in severe OA cartilage. Inhibition of VEGF by shRNA protects chondrocytes from TNF-α-induced hypertrophy. Knockdown of VEGF suppresses TNF-α-induced phosphorylation of ERK1/2 in chondrocytes. VEGF inhibition delays OA progression in rat model in vivo. Inhibition of VEGF may be a potential therapeutic approach for OA patients.
Publisher: Wiley
Date: 06-2006
DOI: 10.1111/J.1445-2197.2006.03757.X
Abstract: In Australia, the most frequently used hemiarthroplasty prosthesis for the management of displaced intracapsular femoral neck fractures is the Uncemented Austin Moore (UAM). Despite concerns regarding poor functional outcomes and increased early revision rates associated with the UAM prosthesis, apprehension regarding the systemic side-effects of polymethylmethacrylate cement implantation in the elderly patient continues to influence prosthesis selection. This study examines the incidence of early prosthesis related complications after UAM and Cemented Thompson (CT) hemiarthroplasty procedures for the management of femoral neck fractures. A multicentre retrospective review of charts and radiographs was conducted in 1118 unipolar hemiarthroplasty implantations to determine early complications associated with the CT and UAM prostheses over a 6-year period in five Queensland public hospitals. Intraoperative periprosthetic fractures were sustained in 11.8% of UAM and 1.8% of CT implantations (P < 0.0001). Intraoperative periprosthetic fractures were associated with an increased requirement for reoperation within 1 month of the index procedure (P = 0.05). No statistical difference in the incidence of intraoperative periprosthetic fractures could be observed between the hospitals participating, regardless of the proportional use of each prosthesis. Early dislocation rates were similar for the UAM and CT prostheses. The intraoperative mortality rate attributable to the use of polymethylmethacrylate cement during hip hemiarthroplasty was 1/738 (0.14%). The results of this study support the use of the CT prosthesis for the management of femoral neck fractures to reduce the high incidence of intraoperative periprosthetic fractures and associated requirements for early reoperation experienced with the UAM.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1111/J.1538-7836.2005.01457.X
Abstract: A prospective randomized double-blind placebo-controlled study was undertaken to determine the efficacy and mechanism of action of two antifibrinolytic drugs aprotinin and epsilon aminocaproic acid (EACA) in reducing blood loss in primary unilateral total hip arthroplasty (THA). Aprotinin was administered as a bolus of 2 x 10(6) kallikrein inhibitor units (KIU) followed by 0.5 x 10(6) KIU h(-1) for 3 h, EACA was given as 10 g over 30 min followed by 5 g over 3 h. The median postoperative blood loss 24 h postoperatively was reduced from 450 mL in the placebo group to 180 mL for aprotinin (60% reduction, P < 0.001) and to 210 mL for EACA (53% reduction, P < 0.01). In this population, there was no reduction in the perioperative transfusion requirements. The mechanism of both drugs was independent of platelets as indicated by flow cytometric measurement of change of their expression of P-selectin, platelet-monocyte aggregates, V/Va and CD40 ligand. There were no thrombotic or infective complications and no adverse events were attributable to use of either drug. Infusion of either aprotinin or EACA at the doses described is a safe and effective means of reducing blood loss after THA. These therapies provide a means of reducing blood loss in THA patients.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.BONE.2012.12.042
Abstract: Determining the properties and integrity of subchondral bone in the developmental stages of osteoarthritis, especially in a form that can facilitate real-time characterization for diagnostic and decision-making purposes, is still a matter for research and development. This paper presents relationships between near infrared absorption spectra and properties of subchondral bone obtained from 3 models of osteoarthritic degeneration induced in laboratory rats via: (i) menisectomy (MSX) (ii) anterior cruciate ligament transaction (ACL) and (iii) intra-articular injection of mono-ido-acetate (1mg) (MIA), in the right knee joint, with 12 rats per model group (N=36). After 8weeks, the animals were sacrificed and knee joints were collected. A custom-made diffuse reflectance NIR probe of diameter 5mm was placed on the tibial surface and spectral data were acquired from each specimen in the wavenumber range 4000-12500cm(-1). After spectral acquisition, micro computed tomography (micro-CT) was performed on the s les and subchondral bone parameters namely: bone volume (BV) and bone mineral density (BMD) were extracted from the micro-CT data. Statistical correlation was then conducted between these parameters and regions of the near infrared spectra using multivariate techniques including principal component analysis (PCA), discriminant analysis (DA), and partial least squares (PLS) regression. Statistically significant linear correlations were found between the near infrared absorption spectra and subchondral bone BMD (R(2)=98.84%) and BV (R(2)=97.87%). In conclusion, near infrared spectroscopic probing can be used to detect, qualify and quantify changes in the composition of the subchondral bone, and could potentially assist in distinguishing healthy from OA bone as demonstrated with our laboratory rat models.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2007
Publisher: Informa UK Limited
Date: 2007
DOI: 10.1080/03008200601074778
Abstract: This article outlines the motivation and preliminary investigations into a novel method of characterizing cartilage health for potential in vivo application. Current in vivo indentation techniques, which primarily rely on stiffness measurements based on axial data, are unable to adequately distinguish between healthy and degraded tissue. The present in vitro study investigates the effects of controlled artificial degradation on the effective surface stretch, comparing the results with those obtained from the peripheral cartilage surrounding focal osteoarthritis. Results suggest that this technique is highly sensitive, showing a maximum range of 14% effective surface stretch in a normal joint compared with 42% for axial strain measurements. We further demonstrated that the technique can discriminate between degenerative changes and the intrinsic variations in cartilage properties across the normal joint. From these investigations we propose that the relationship between indentation and the in-plane strain field under the indenter can better distinguish degraded tissue than the currently used stiffness techniques.
Publisher: IOP Publishing
Date: 08-07-2008
DOI: 10.1088/0031-9155/53/15/008
Abstract: The ability to quantify and qualify the progression of joint degeneration is becoming increasingly important in surgery. This paper examines the patterns of relative ultrasound reflection from normal, artificially and naturally degraded cartilage-on-bone, particularly investigating the potential of the ratio of reflection coefficients from the surface and osteochondral junction in distinguishing normal from osteoarthritic tissue. To this end, the reflection coefficients from the articular surface and osteochondral junction of normal cartilage-on-bone s les were calculated and compared to s les after the removal of proteoglycans, disruption of the collagen meshwork, delipidization of the articular surface and mechanical abrasion. Our results show that the large variation across normal and degraded joint s les negates the use of an isolated bone reflection measurement and to a lesser extent, an isolated surface reflection. The relative surface to bone reflections, calculated as a ratio of reflection coefficients, provided a more consistent and statistically significant (p < 0.001) method for distinguishing each type of degradation, especially osteoarthritic degradation, and due to the complementary relationship between surface and bone reflections was found to be an effective method for distinguishing degraded from normal tissue in the osteoarthritic joint, independent of the site of initiation of the osteoarthritic process.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.IJOM.2012.06.002
Abstract: This article reviews the literature on the outcome of flapless surgery for dental implants in the posterior maxilla. The literature search was carried out in using the keywords: flapless, dental implants and maxilla. A hand search and Medline search were carried out on studies published between 1971 and 2011. The authors included research involving a minimum of 15 dental implants with a follow-up period of 1 year, an outcome measurement of implant survival, but excluded studies involving multiple simultaneous interventions, and studies with missing data. The Cochrane approach for cohort studies and Oxford Centre for Evidence-Based Medicine were applied. Of the 56 published papers selected, 14 papers on the flapless technique showed high overall implant survival rates. The prospective studies yielded 97.01% (95% CI: 90.72-99.0) while retrospective studies or case series illustrated 95.08% (95% CI: 91.0-97.93) survival. The average of intraoperative complications was 6.55% using the flapless procedure. The limited data obtained showed that flapless surgery in posterior maxilla areas could be a viable and predictable treatment method for implant placement. Flapless surgery tends to be more applicable in this area of the mouth. Further long-term clinical controlled studies are needed.
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.BIOSYSTEMS.2008.05.030
Abstract: Osteoarthritis (OA), the most common form of arthritis is a degenerative joint disease, which causes severe long-term pain and physical disability. It is becoming more important to improve diagnosis and understanding of the disease process and subsequently develop new intervention to delay or even reverse the disease progress. Our study was designed to combine two relatively novel treatment techniques, autologous chondrocyte transplantation (ACT) and proposed application of medical remedies based on surface-active phospholipids. To this end we exposed chondrocyte to culture environments with mixtures of culture medium and phospholipid solutions. Following various culture periods, cell survival and well-being were determined by measuring proliferation and assessing morphological features, and comparing these with the behaviour of cells grown in classical which were not mixed with surfactant, i.e., control culture medium. Scanning electron microscopy and light microscopy demonstrate that the cells exposed to mixtures with surfactant were as healthy as those in the control environment with polygonal morphology, while proliferation assay indicated a noticeably higher level of proliferation over similar periods, for cells cultured in media that was mixed with surfactants. Also, the cells in media with unsaturated surfactants responded better than those cultured in mixtures containing saturated surfactant.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3TC32057J
Abstract: The anisotropic growth of gold nanoparticles under the influence of gemini surfactants is studied. The growth mechanism is discussed using electronic structure calculation modeling.
Publisher: Elsevier BV
Date: 07-2016
Publisher: Elsevier BV
Date: 04-2012
DOI: 10.1016/J.ARTH.2011.08.002
Abstract: We describe a scaling method for templating digital radiographs using conventional acetate templates independent of template magnification without the need for a calibration marker. The mean magnification factor for the radiology department was determined (119.8% range, 117%-123.4%). This fixed magnification factor was used to scale the radiographs by the method described. Thirty-two femoral heads on postoperative total hip arthroplasty radiographs were then measured and compared with the actual size. The mean absolute accuracy was within 0.5% of actual head size (range, 0%-3%) with a mean absolute difference of 0.16 mm (range, 0-1 mm SD, 0.26 mm). Intraclass correlation coefficient showed excellent reliability for both interobserver and intraobserver measurements with intraclass correlation coefficient scores of 0.993 (95% CI, 0.988-0.996) for interobserver measurements and intraobserver measurements ranging between 0.990 and 0.993 (95% CI, 0.980-0.997).
Publisher: Elsevier BV
Date: 2010
Publisher: Oxford University Press (OUP)
Date: 07-2014
DOI: 10.1093/RHEUMATOLOGY/KEU262
Abstract: The aim of this study was to test the possible involvement, relevance and significance of dentin matrix protein 1 (DMP1) in chondrocyte redifferentiation and OA. To examine the function of DMP1 in vitro, bone marrow stromal cells (BMSCs) and articular chondrocytes (ACs) were isolated and differentiated in micromasses in the presence or absence of DMP1 small interfering RNA and analysed for chondrogenic phenotype. The association of DMP1 expression with OA progression was analysed time dependently in the OA menisectomy rat model and in grade-specific OA human s les. It was found that DMP1 was strongly related to chondrogenesis, which was evidenced by the strong expression of DMP1 in the 14.5-day mouse embryonic cartilage development stage and in femoral heads of post-natal days 0 and 4. In vitro chondrogenesis in BMSCs and ACs was accompanied by a gradual increase in DMP1 expression at both the gene and protein levels. In addition, knockdown of DMP1 expression led to decreased chondrocyte marker genes, such as COL2A1, ACAN and SOX9, and an increase in the expression of COL10A and MMP13 in ACs. Moreover, treatment with IL-1β, a well-known catabolic culprit of proteoglycan matrix loss, significantly reduced the expression of DMP1. Furthermore, we also observed the suppression of DMP1 protein in a grade-specific manner in knee joint s les from patients with OA. In the menisectomy-induced OA model, an increase in the Mankin score was accompanied by the gradual loss of DMP1 expression. Observations from this study suggest that DMP1 may play an important role in maintaining the chondrogenic phenotype and its possible involvement in altered cartilage matrix remodelling and degradation in disease conditions like OA.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 10-0009
DOI: 10.1016/J.KNEE.2008.05.003
Abstract: We report the case of a 44-year-old man who underwent a partial medial meniscectomy for a meniscal tear whose postoperative course was complicated by the development of heterotopic ossification (HO) within the medial arthroscopic portal. Following a routine initial procedure, the patient presented with ongoing pain and a palpable, painful lump around the previous medial arthroscopy portal. Plain radiographs and MRI were suggestive of a bony structure within the soft tissues. Histopathological examination at repeat arthroscopy confirmed osseous tissue consistent with HO. Recovery after the second procedure was rapid and resulted in normal knee function and complete pain relief. HO within an arthroscopy portal is a rare complication following arthroscopic partial meniscectomy in the knee and has not previously been described in the literature.
Publisher: Medical Journals Sweden AB
Date: 2005
DOI: 10.1080/17453670510041448
Abstract: Metal particles are generated during bone preparation in knee arthroplasty. These particles may produce third-body wear, or may have a role in osteolysis. Knowledge of their characteristics may help in the development of methods to reduce the amount of metal debris during bone cutting procedures. We performed bony resection of the distal femur and proximal tibia on 15 pig knees, simulating a total knee arthroplasty (TKA). Metal debris was collected from the saw blades, cutting blocks and bone surfaces and cleaned for microanalysis. The average loss of metal from the saw blades was 1.13 mg. The average volume of a wear particle was 3.4 x 10(-16) m(3). From this, it was estimated that approximately 500,000 particles are released from the saw blade alone. Material analysis of the particles indicated that the majority originated from the metallic cutting guides, suggesting that many millions of wear particles would be generated during the surgical procedure. Two particle shapes predominated: platelet shape and ploughed shape. Wear particles are produced during resection for a TKA. These may enter the artificial articulation and cause accelerated wear and macrophage activation. Redesign of cutting blocks and saw blades may reduce the amount of debris produced during surgery.
Publisher: Wiley
Date: 02-2017
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.BIOMATERIALS.2014.06.038
Abstract: The osteoimmunomodulatory property of bone biomaterials is a vital property determining the in vivo fate of the implants. Endowing bone biomaterials with favorable osteoimmunomodulatory properties is of great importance in triggering desired immune response and thus supports the bone healing process. Magnesium (Mg) has been recognized as a revolutionary metal for applications in orthopedics due to it being biodegradable, biocompatible, and having osteoconductive properties. However, Mg's high rate of degradation leads to an excessive inflammatory response and this has restricted its application in bone tissue engineering. In this study, β-tricalcium phosphate (β-TCP) was used to coat Mg scaffolds in an effort to modulate the detrimental osteoimmunomodulatory properties of Mg scaffolds, due to the reported favorable osteoimmunomodulatory properties of β-TCP. It was noted that macrophages switched to the M2 extreme phenotype in response to the Mg-β-TCP scaffolds, which could be due to the inhibition of the toll like receptor (TLR) signaling pathway. VEGF and BMP2 were significantly upregulated in the macrophages exposed to Mg-β-TCP scaffolds, indicating pro-osteogenic properties of macrophages in β-TCP modified Mg scaffolds. This was further demonstrated by the macrophage-mediated osteogenic differentiation of bone marrow stromal cells (BMSCs). When BMSCs were stimulated by conditioned medium from macrophages cultured on Mg-β-TCP scaffolds, osteogenic differentiation of BMSCs was significantly enhanced whereas osteoclastogenesis was inhibited, as indicated by the downregualtion of MCSF, TRAP and inhibition of the RANKL/RANK system. These findings suggest that β-TCP coating of Mg scaffolds can modulate the scaffold's osteoimmunomodulatory properties, shift the immune microenvironment towards one that favors osteogenesis over osteoclastogenesis. Endowing bone biomaterials with favorable osteoimmunomodulatory properties can be a highly valuable strategy for the development or modification of advanced bone biomaterials.
Publisher: Medical Journals Sweden AB
Date: 30-06-2010
Publisher: Mary Ann Liebert Inc
Date: 11-2005
Abstract: Cell attachment, expansion, and migration in three-dimensional biomaterials are crucial steps for effective delivery of osteogenic cells into bone defects. Complexes composed of vitronectin (VN), insulin-like growth factors (IGFs), and insulin growth factor-binding proteins (IGFBPs) have been reported to enhance cell attachment, proliferation, and migration in a variety of cell lines in vitro. The aim of this study was to examine whether prebound complexes of VN and IGFs +/- IGFBPs could facilitate human osteoblast serum-free expansion in vitro and enhance cell attachment, proliferation, and migration in three-dimensional biomaterial constructs. Human osteoblasts derived from alveolar bone chips and the established human osteoblast cell line Saos-2 were used. These cells were seeded on tissue culture plates and porous scaffolds of type I collagen sponges and polyglycolic acid (PGA), which had been coated with VN +/- IGFBP-5 +/- IGF-I. Cell attachment, proliferation, and migration were evaluated by cell counting, confocal microscopy, and scanning electron microscopy. The number of attached human osteoblasts was significantly higher in VN-coated polystyrene culture dishes. Furthermore, significant increases in cell proliferation were observed when growth factors were bound to these surfaces in the presence of VN. In the two scaffold materials examined, greater cell attachment was found in type I collagen sponges compared with PGA scaffolds. However, coating the scaffolds with complexes composed of VN + IGF-I or VN + IGFBP-5 + IGF-I enhanced cell attachment on PGA. Moreover, the presence of VN + IGFBP-5 + IGF-I resulted in significantly greater osteoblast migration into deep pore areas as compared with untreated scaffolds or scaffolds treated with fetal calf serum. These results demonstrated that complexes of VN + IGFBP-5 + IGF-I can be used to expand osteoblasts in vitro under serum-free conditions and enhance the attachment and migration of human osteoblasts in three-dimensional culture. This in turn suggests a potential application in surface modification of biomaterials for tissue reconstruction.
Publisher: BMJ
Date: 02-08-2006
Publisher: Elsevier BV
Date: 06-2003
DOI: 10.1016/S0883-5403(03)00072-X
Abstract: Much evidence supports the hypothesis that surface-active phospholipid (SAPL), which imparts the thin hydrophobic outermost lining to the normal articular surface, is the boundary lubricant reducing friction to remarkably low levels. We review this evidence and further hypothesize that SAPL produced in type B synoviocytes will also lubricate prostheses after implantation. This could explain why implanted hips display far less wear than hips in simulated wear trials do, even using protein as the lubricant whereas rougher surfaces can be tolerated in vivo. We introduce the concept that a deficiency of SAPL might explain the selective failure of prostheses just as osteoarthritic articular surfaces are deficient. This, in turn, leads to the replenishment of SAPL, as tested in OA, and the concept of prelubricating prostheses before implantation.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.ARTH.2008.12.009
Abstract: Routine postsurgery assessment of primary total hip arthroplasty (THA) is recommended in many countries. Whether the benefits of this activity are justified by the costs is not known. We used a decision-analytic Markov model to compare the costs and health outcomes of 3 different follow-up strategies after primary THA. If there is no routine follow-up of patients for 7 years after primary THA, there would be cost savings between AU$6.5 and $11.9 million and gains of between 1.8 and 8.8 quality-adjusted life years. Policy makers should investigate less resource-intensive alternatives to common routine postsurgical assessment.
Publisher: Wiley
Date: 26-07-2006
Publisher: Medical Journals Sweden AB
Date: 11-05-2011
Publisher: SAGE Publications
Date: 08-06-2013
Abstract: The repair of articular cartilage typically involves the repair of cartilage–subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage–subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite–β-tricalcium phosphate (HA–TCP), poly lactic-glycolic acid (PLGA)-HA–TCP dual-layered composite scaffolds (PLGA/HA–TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA–TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA–TCP scaffolds. Furthermore, HA–TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA–TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2013
DOI: 10.1007/S00109-012-0953-5
Abstract: We hypothesised that a potentially disease-modifying osteoarthritis (OA) drug such as hyaluronic acid (HA) given in combination with anti-inflammatory signalling agents such as mitogen-activated protein kinase kinase-extracellular signal-regulated kinase (MEK-ERK) signalling inhibitor (U0126) could result in additive or synergistic effects on preventing the degeneration of articular cartilage. Chondrocyte differentiation and hypertrophy were evaluated using human OA primary cells treated with either HA or U0126, or the combination of HA + U0126. Cartilage degeneration in menisectomy (MSX) induced rat OA model was investigated by intra-articular delivery of either HA or U0126, or the combination of HA + U0126. Histology, immunostaining, RT-qPCR, Western blotting and zymography were performed to assess the expression of cartilage matrix proteins and hypertrophic markers. Phosphorylated ERK (pERK)1/2-positive chondrocytes were significantly higher in OA s les compared with those in healthy control suggesting the pathological role of that pathway in OA. It was noted that HA + U0126 significantly reduced the levels of pERK, chondrocyte hypertrophic markers (COL10 and RUNX2) and degenerative markers (ADAMTs5 and MMP-13), however, increased the levels of chondrogenic markers (COL2) compared to untreated or the application of HA or U0126 alone. In agreement with the results in vitro, intra-articular delivery of HA + U0126 showed significant therapeutic improvement of cartilage in rat MSX OA model compared with untreated or the application of HA or U0126 alone. Our study suggests that the combination of HA and MEK-ERK inhibition has a synergistic effect on preventing cartilage degeneration.
Publisher: Medical Journals Sweden AB
Date: 2007
DOI: 10.1080/17453670710013852
Abstract: The identity of the vital active ingredient within synovial fluid (SF)--to which we owe the near frictionless performance of diarthrodial joints--has been the quest of researchers for many years. Initially, hyaluronic acid (HA) was thought to be the lubricant, but it has been shown not to possess the load-bearing ability required within the physiological joint. The glycoprotein fraction of synovial fluid (lubricin) has been shown to have the same lubricating ability as synovial fluid. All or part of this is thought to be due to the surface-active phospholipids (SAPLs) present in lubricin. We characterized the SAPLs adsorbed on the surface of retrieved prostheses which have been implicated as the boundary lubricant. Rinsing fluids collected from the bearing surfaces of 40 prostheses removed from hip and knee revision operations were analyzed using high-performance liquid chromatography (HPLC). SAPLs were detected on all retrieved implants. During the study, 8 different species of phosphatidylcholines were identified. We also determined the relative concentration of each species, which suggested that the unsaturated SAPL species predominate. It is of value to know the identity of the lubricating constituents of SF, not only for the future development of artificial joints, but also in developing cures for several disease processes in which lubrication plays a role.
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2019
DOI: 10.1101/853556
Abstract: Despite immense promise, engineering of stable cartilage tissue from bone marrow-derived stromal cells (BMSCs, also known as bone marrow-derived “mesenchymal stem cells”) remains elusive. Relative cartilage-like matrix deposition is commonly used to guide BMSC chondrogenic optimisation efforts. However, matrix deposition is heterogeneous in most models, and notably, it lags behind cell fate decisions. We reason that the lag time between cell fate decision and matrix accumulation, coupled with matrix heterogeneity, has obscured basic BMSC biological characteristics, such as differentiation kinetics. Here, we utilize a customized microwell platform to assemble hundreds of small-diameter BMSC micro -pellets and characterized chondrogenic differentiation kinetics in response to the canonical signaling molecule, transforming growth factor-β1 (TGF-β1). Micro -pellets provide a homogeneous readout, and our experimental design accounts for the significant time delay between growth factor signal and deposition of cartilage-like matrix. While 14-to-21-day induction protocols are routine, BMSC micro -pellet cultures reveal that a single day of TGF-β1 exposure was sufficient to trigger chondrogenic differentiation cascades resulting in outcomes similar to micro -pellets exposed to TGF-β1 for 21 days. RNA-sequencing analysis demonstrated that one day of TGF-β1 exposure was also sufficient to induce hypertrophic cascades in BMSC, not observed in articular chondrocytes. Refocusing chondrogenic induction optimisation efforts from weeks to the first hours or days of culture, using homogeneous model systems, may benefit efforts to build stable cartilage formed by BMSCs. The macro -pellet model, and assumptions generated using it, have permeated BMSC-based cartilage tissue engineering strategies since the 1990s. Using a micro -pellet model, we show that BMSC chondrogenic kinetics are significantly more rapid than historical macro -pellets data suggests, and that BMSC chondrogenic and hypertrophic commitment is instructed by a single day of TGF-β1 exposure. This highly relevant study demonstrates that: (1) macro -pellets, which are large heterogeneous tissue models confound the differentiation kinetics visible in micro -pellet models (2) induction strategies should focus on the first hours or days of culture (3) even a single day of TGF-β1 exposure drives BMSC to form hypertrophic tissue in vivo , requiring early intervention to prevent hypertrophy and (4) articular chondrocytes and BMSCs respond distinctly to TGF-β1.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2016
DOI: 10.1007/S00223-016-0125-7
Abstract: This study aimed to identify the microRNAs associated with sclerotic status of subchondral bone in the pathogenesis of osteoarthritis (OA). Total RNA was extracted from non-sclerotic and sclerotic OA subchondral bone from patients undergoing knee replacement surgeries. miRCURY™ LNA miRNA chip and qRT-PCR were used to profile and validate differential microRNA expression. In addition, we further confirmed profiles of altered miRNAs in an OA rat meniscectomy animal model and their putative targets of the miRNAs were predicted using ingenuity (IPA) software. Finally, five short-listed miRNAs were reactivated by transient in vitro overexpression (miRNA mimics) in subchondral bone osteoblasts and their phenotypes were assessed. Functional screening identified 30 differentiated miRNAs in sclerotic subchondral bone compared to non-sclerotic bone of OA patients. Data integration resulted in confirmation of the eight miRNAs, with aberrant expression in independent human OA bone s le set. In silico analysis (IPA) identified 732 mRNA transcripts as putative targets of the eight altered miRNAs, of which twenty genes were validated to be differentially expressed in sclerotic compared to non-sclerotic bone s les. Out of eight dysregulated miRNA's, five of them showed consistent time-dependent downregulation in a rat OA model. Furthermore, synthetic miR-199a-3p, miR-199a-5p, miR-590-5p, and miR-211-5p mimics rescued the abnormal osteoarthritic subchondral bone osteoblast gene expression and mineralization. We have identified four novel miRNAs that play important roles in subchondral bone pathogenesis in OA. Additional studies are required to develop these miRNAs into therapeutic modalities for OA.
Publisher: Wiley
Date: 03-11-2009
Abstract: Articular cartilage is a highly hydrated tissue with depth-dependent cellular and matrix properties that provide low-friction load bearing in joints. However, the structure and function are frequently lost and there is insufficient repair response to regenerate high-quality cartilage. Several hydrogel-based tissue-engineering strategies have recently been developed to form constructs with biomimetic zonal variations to improve cartilage repair. Modular hydrogel systems allow for systematic control over hydrogel properties, and advanced fabrication techniques allow for control over construct organization. These technologies have great potential to address many unanswered questions involved in prescribing zonal properties to tissue-engineered constructs for cartilage repair.
Publisher: SAGE Publications
Date: 12-02-2010
Abstract: The Rim Cutter™ (Stryker Orthopedics, Mahwah, New Jersey) is a tool designed to cut a ledge inside the rim of the acetabulum, onto which a precisely trimmed, cemented, flanged cup can be fitted. The aim was to investigate the effect of the Rim Cutter on the intra-acetabular cement mantle pressure and the depth of cement penetration during cup insertion. The study had two parts. In the first part, hemi-pelvis models were fitted with pressure sensors. Pressure in the acetabulum was measured on insertion of a conventional cemented flanged cup with and without the use of a Rim Cutter to prepare the rim of the acetabulum. The second part assessed cement penetration when the same cups were inserted into a foam shell model. The shell was mounted in a jig and had holes drilled in it the distance that cement penetrated into the holes was measured. A significant increase in cement pressure at the apex ( p = 0.04) and the rim ( p = 0.004) is seen when the Rim Cutter is used. Cement penetration in the Rim Cutter group was significantly increased at the rim of the acetabulum ( p = 0.003). Insertion of a flanged cup after the acetabulum is prepared with the Rim Cutter leads to a significant increase in cement pressure and penetration during cup insertion in vitro when compared with conventional flanged cups.
Publisher: IOP Publishing
Date: 04-01-2012
DOI: 10.1088/0031-9155/57/2/547
Abstract: Early-stage treatments for osteoarthritis are attracting considerable interest as a means to delay, or avoid altogether, the pain and lack of mobility associated with late-stage disease, and the considerable burden that it places on the community. With the development of these treatments comes a need to assess the tissue to which they are applied, both in trialling of new treatments and as an aid to clinical decision making. Here, we measure a range of mechanical indentation, ultrasound and near-infrared spectroscopy parameters in normal and osteoarthritic bovine joints in vitro to describe the role of different physical phenomena in disease progression, using this as a basis to investigate the potential value of the techniques as clinical tools. Based on 72 s les we found that mechanical and ultrasound parameters showed differences between fibrillated tissue, macroscopically normal tissue in osteoarthritic joints, and normal tissue, yet did were unable to differentiate degradation beyond that which was visible to the naked eye. Near-infrared spectroscopy showed a clear progression of degradation across the visibly normal osteoarthritic joint surface and as such, was the only technique considered useful for clinical application.
Publisher: Mary Ann Liebert Inc
Date: 12-2013
Publisher: Wiley
Date: 05-01-2011
DOI: 10.1002/JBM.B.31779
Abstract: Poly(lactide-co-glycolide) (PLGA) beads have been widely studied as a potential drug rotein carrier. The main shortcomings of PLGA beads are that they lack bioactivity and controllable drug-delivery ability, and their acidic degradation by-products can lead to pH decrease in the vicinity of the implants. Akermanite (AK) (Ca(2) MgSi(2) O(7) ) is a novel bioactive ceramic which has shown excellent bioactivity and degradation in vivo. This study aimed to incorporate AK to PLGA beads to improve the physiochemical, drug-delivery, and biological properties of PLGA beads. The microstructure of beads was characterized by SEM. The effect of AK incorporating into PLGA beads on the mechanical strength, apatite-formation ability, the loading and release of BSA, and the proliferation, and differentiation of bone marrow stromal cells (BMSCs) was investigated. The results showed that the incorporation of AK into PLGA beads altered the anisotropic microporous structure into homogenous one and improved their compressive strength and apatite-formation ability in simulated body fluids (SBF). AK neutralized the acidic products from PLGA beads, leading to stable pH value of 7.4 in biological environment. AK led to a sustainable and controllable release of bovine serum albumin (BSA) in PLGA beads. The incorporation of AK into PLGA beads enhanced the proliferation and alkaline phosphatase activity of BMSCs. This study implies that the incorporation of AK into PLGA beads is a promising method to enhance their physiochemical and biological property. AK/PLGA composite beads are a potential bioactive drug-delivery system for bone tissue repair.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.AJIC.2012.11.015
Abstract: Surgical site infection (SSI) is associated with substantial costs for health services, reduced quality of life, and functional outcomes. The aim of this study was to evaluate the cost-effectiveness of strategies claiming to reduce the risk of SSI in hip arthroplasty in Australia. Baseline use of antibiotic prophylaxis (AP) was compared with no antibiotic prophylaxis (no AP), antibiotic-impregnated cement (AP + ABC), and laminar air operating rooms (AP + LOR). A Markov model was used to simulate long-term health and cost outcomes of a hypothetical cohort of 30,000 total hip arthroplasty patients from a health services perspective. Model parameters were informed by the best available evidence. Uncertainty was explored in probabilistic sensitivity and scenario analyses. Stopping the routine use of AP resulted in over Australian dollars (AUD) $1.5 million extra costs and a loss of 163 quality-adjusted life years (QALYs). Using antibiotic cement in addition to AP (AP + ABC) generated an extra 32 QALYs while saving over AUD $123,000. The use of laminar air operating rooms combined with routine AP (AP + LOR) resulted in an AUD $4.59 million cost increase and 127 QALYs lost compared with the baseline comparator. Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalized patients, save lives, and enhance resource allocation. Based on this evidence, the use of laminar air operating rooms is not recommended.
Publisher: Wiley
Date: 29-05-2008
Publisher: Elsevier BV
Date: 06-2004
Publisher: Research Square Platform LLC
Date: 16-10-2023
Publisher: Springer Science and Business Media LLC
Date: 16-07-2016
DOI: 10.1007/S11926-016-0605-9
Abstract: Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and lification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2020
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.ACTBIO.2007.10.006
Abstract: Regeneration of bone, cartilage and osteochondral tissues by tissue engineering has attracted intense attention due to its potential advantages over the traditional replacement of tissues with synthetic implants. Nevertheless, there is still a dearth of ideal or suitable scaffolds based on porous biomaterials, and the present study was undertaken to develop and evaluate a useful porous composite scaffold system. Here, hydroxyapatite (HA)/tricalcium phosphate (TCP) scaffolds (average pore size: 500 microm porosity: 87%) were prepared by a polyurethane foam replica method, followed by modification with infiltration and coating of poly(lactic-co-glycolic acid) (PLGA). The thermal shock resistance of the composite scaffolds was evaluated by measuring the compressive strength before and after quenching or freezing treatment. The porous structure (in terms of pore size, porosity and pore interconnectivity) of the composite scaffolds was examined. The penetration of the bone marrow stromal stem cells into the scaffolds and the attachment of the cells onto the scaffolds were also investigated. It was shown that the PLGA incorporation in the HA/TCP scaffolds significantly increased the compressive strength up to 660 kPa and the residual compressive strength after the freezing treatment decreased to 160 kPa, which was, however, sufficient for the scaffolds to withstand subsequent cell culture procedures and a freeze-drying process. On the other hand, the PLGA coating on the strut surfaces of the scaffolds was rather thin (<5 microm) and apparently porous, maintaining the high open porosity of the HA/TCP scaffolds, resulting in desirable migration and attachment of the bone marrow stromal stem cells, although a thicker PLGA coating would have imparted a higher compressive strength of the PLGA-coated porous HA/TCP composite scaffolds.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ACTBIO.2019.01.006
Abstract: Exosomes are extracellular nanovesicles that play an important role in cellular communication. The modulatory effects of bone morphogenetic protein 2 (BMP2) on macrophages have encouraged the functionalization of scaffolds through the integration of the exosomes from the BMP2-stimulated macrophages to avoid ectopic bone formation and reduce adverse effects. To determine the functionality of exosomal nanocarriers from macrophages after BMP2 stimulation, we isolated the exosomes from Dulbecco's modified Eagle's medium (DMEM)- or BMP2-stimulated macrophages and evaluated their effects on osteogenesis. Morphological characterization of the exosomes derived from DMEM- or BMP2-treated macrophages revealed no significant differences, and the bone marrow-derived mesenchymal stromal cells showed similar cellular uptake patterns for both exosomes. In vitro study using BMP2/macrophage-derived exosomes indicated their beneficial effects on osteogenic differentiation. To improve the bio-functionality for titanium implants, BMP2/macrophage-derived exosomes were used to modify titanium nanotube implants to favor osteogenesis. The incorporation of BMP2/macrophage-derived exosomes dramatically increased the expression of early osteoblastic differentiation markers, alkaline phosphatase (ALP) and BMP2, indicative of the pro-osteogenic role of the titanium nanotubes incorporated with BMP2/macrophage-derived exosomes. The titanium nanotubes functionalized with BMP2/macrophage-derived exosomes activated autophagy during osteogenic differentiation. In conclusion, the exosome-integrated titanium nanotube may serve as an emerging functional material for bone regeneration. STATEMENT OF SIGNIFICANCE: The clinical application of bone morphogenetic protein 2 (BMP2) is often limited by its side effects. Exosomes are naturally secreted nanosized vesicles derived from cells and play an important role in intercellular communication. The contributions of this study include (1) the demonstration of the potential regulatory role of BMP2/macrophage-derived exosomes on the osteogenic differentiation of mesenchymal stromal cells (MSCs) (2) fabrication of titanium nanotubes incorporated with exosomes (3) new insights into the application of titanium nanotube-based materials for the safe use of BMP2.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.KNEE.2009.02.006
Abstract: Bone sarcomas are the fourth most common cancer in in iduals under 25 years. Limb salvage procedures are popular for the treatment of osteosarcomas as they have functional and physiological benefits over traditional utative procedures. The objective of this study was to apply disease specific measures to a group of intra-articular knee osteosarcoma patients and to evaluate structural and treatment variables predictive of the functional outcome scores. Twenty patients (10 female, 10 male) treated with tumour resection and endoprosthetic knee arthroplasty took part in the study. The Musculoskeletal Tumour Society (MSTS) rating scale and the Toronto Extremity Salvage Score (TESS) were used to assess impairment and disability respectively. Impairment was recorded as 83% and disability was recorded as 86% suggesting moderate to high function following limb salvage surgery. Task difficulty was shown to increase for activities requiring large knee flexion angles, presumably due to increased patellofemoral forces. Bivariate correlations revealed that loss of quadriceps musculature, knee extension strength and knee flexion range of motion were parameters moderately associated with the assessment instruments. ANOVA revealed no significant differences in impairment (P=0.962) or disability (P=0.411) between the differing types of prostheses. In conclusion clinicians and therapists should emphasise restoration of post-surgical range of motion and strength in order to enhance functional recovery.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.ARTH.2007.05.048
Abstract: In some orthopedic procedures, including total knee arthroplasty (TKA), surgeons are exposed to noise generated by powered instruments, with a risk of developing occupational hearing loss. A new saw design, the Stryker Precision system (Stryker, Kalamazoo, Mich), has been developed that may reduce noise during TKA surgery. The new system was tested against a standard Stryker System 5 sagittal saw in simulated TKA surgery using porcine cadaveric femurs, and noise levels from the cuts were measured. The average noise level of the Precision system, L(Aeq) = 81.6 dB(A), was significantly lower than that of the System 5 saw, L(Aeq) = 88.9 dB(A) (P = .003). Calculated 8-hour values for both blade systems were within Health and Safety guidelines. It was concluded that the Precision system produced a lower risk of noise-induced hearing loss than the System 5 saw.
Publisher: Elsevier BV
Date: 09-2013
Publisher: Wiley
Date: 18-05-2010
DOI: 10.1111/J.1365-2362.2010.02289.X
Abstract: Peri-operative cardiac events are common and associated with significant morbidity. A predictive biomarker would assist in pre-operative risk stratification of surgical patients. This study explored the utility of pre-operative measurements of platelet-bound CD40 ligand and other biomarkers for predicting peri-operative cardiac events in total hip or knee arthroplasty. Blood s les were collected from 62 patients prior to surgery and tested for the biomarkers platelet CD40 ligand, platelet factor V/Va, platelet P-selectin, high-sensitivity C-reactive protein, B-type natriuretic peptide and soluble CD40 ligand. The Revised Cardiac Risk Index was also calculated. Patients were then followed up prospectively and screened for peri-operative cardiac events by means of ECG, serial troponin I, a cardiologist's review and an interview at 6 weeks post operation. Six of 62 (9.7%) patients had a cardiac event. Patients who experienced a cardiac event had higher pre-operative platelet CD40 ligand levels as measured by flow cytometry [median 0.55% vs. 0.29% (P = 0.02)]. In this sized s le, platelet CD40L was the only biomarker independently associated with cardiac events (P = 0.02), the area under the receiver-operator characteristic curve being 0.79. In a study of this number of patients, of the six biomarkers tested, only platelet CD40 ligand was found to have a probable association with peri-operative cardiac events in hip and knee arthroplasty.
Publisher: Informa UK Limited
Date: 2200
DOI: 10.1080/03008200600646360
Abstract: A biological and embryological bone induction from epithelial-mesenchymal cell interactions has been noticed in some developing tissues. However, the mechanism for bone formation induced by the epithelial-mesenchymal cell interactions is not clear. The aim of our study was to reveal the role of laminin, vascular endothelial growth factor (VEGF), and bone matrix proteins in mesenchymal cell differentiation during uroepithelial bone induction using a well-established canine model. In this model, a myoperitoneal muscle flap from the abdominal rectus sheath was transplanted into the bladder wall. After 6 weeks, the bladder s les were removed and assessed by histology and immunohistochemistry. This study demonstrated that bone formation occurred in two different directions with two distinct mechanisms. We noted that bone-forming cells in two types of bone formation derived from mesenchymal stem cell differentiation induced either from uroepithelium or bone autoinduction. Laminin was only expressed in peripheral regions of uroepithelium bone formation. Type II collagen was expressed both intracellularly and extracellularly around hypertrophic chondrocytes, whereas VEGF was mostly expressed in proliferating chondrocytes. This study indicates that components in basement membrane like laminin play a role in transitional epithelium-induced differentiation of mesenchymal cells to chondrocytes in muscle tissue. The sequential expression of bone matrix proteins by differentiated osteogenetic cells indicates a subsequent sequence of bone autoinduction.
Publisher: Ivyspring International Publisher
Date: 2012
DOI: 10.7150/IJBS.4221
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.ACTBIO.2013.05.014
Abstract: Polyvinylpyrrolidone-iodine (Povidone-iodine, PVP-I) is widely used as an antiseptic agent for lavation during joint surgery however, the biological effects of PVP-I on cells from joint tissue are unknown. This study examined the biocompatibility and biological effects of PVP-I on cells from joint tissue, with the aim of optimizing cell-scaffold based joint repair. Cells from joint tissue, including cartilage derived progenitor cells (CPC), subchondral bone derived osteoblast and bone marrow derived mesenchymal stem cells (BM-MSC) were isolated. The concentration-dependent effects of PVP-I on cell proliferation, migration and differentiation were evaluated. Additionally, the efficacy and mechanism of a PVP-I loaded bilayer collagen scaffold for osteochondral defect repair was investigated in a rabbit model. A micromolar concentration of PVP-I was found not to affect cell proliferation, CPC migration or extracellular matrix production. Interestingly, micromolar concentrations of PVP-I promote osteogenic differentiation of BM-MSC, as evidenced by up-regulation of RUNX2 and Osteocalcin gene expression, as well as increased mineralization on the three-dimensional scaffold. PVP-I treatment of collagen scaffolds significantly increased fibronectin binding onto the scaffold surface and collagen type I protein synthesis of cultured BM-MSC. Implantation of PVP-I treated collagen scaffolds into rabbit osteochondral defect significantly enhanced subchondral bone regeneration at 6 weeks post-surgery compared with the scaffold alone (subchondral bone histological score of 8.80±1.64 vs. 3.8±2.19, p<0.05). The biocompatibility and pro-osteogenic activity of PVP-I on the cells from joint tissue and the enhanced subchondral bone formation in PVP-I treated scaffolds would thus indicate the potential of PVP-I for osteochondral defect repair.
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.CLINBIOMECH.2007.04.013
Abstract: Relative indentation characteristics are commonly used for distinguishing between normal healthy and degraded cartilage. The application of this parameter in surgical decision making and an appreciation of articular cartilage biomechanics has prompted us to hypothesise that it is difficult to define a reference stiffness to characterise normal articular cartilage. This hypothesis is tested for validity by carrying out biomechanical indentation of articular cartilage s les that are characterised as visually normal and degraded relative to proteoglycan depletion and collagen disruption. Compressive loading was applied at known strain rates to visually normal, artificially degraded and naturally osteoarthritic articular cartilage and observing the trends of their stress-strain and stiffness characteristics. While our results demonstrated a 25% depreciation in the stiffness of in idual s les after proteoglycan depletion, they also showed that when compared to the stiffness of normal s les only 17% lie outside the range of the stress-strain behaviour of normal s les. We conclude that the extent of the variability in the properties of normal s les, and the degree of overlap (81%) of the biomechanical properties of normal and degraded matrices demonstrate that indentation data cannot form an accurate basis for distinguishing normal from abnormal articular cartilage s les with consequences for the application of this mechanical process in the clinical environment.
Publisher: Medical Journals Sweden AB
Date: 09-11-2011
Publisher: SAGE Publications
Date: 03-02-2023
DOI: 10.1177/09544119231152351
Abstract: Standard practice for acetabular component placement in total hip arthroplasty (THA) is to medialise the acetabular component. Bone preservation techniques during primary THA are beneficial for possible future revisions. The goal of this study is to examine the effect of downsizing and minimising medialisation of the acetabular component on bone resection volume. The volume of bone resected during acetabular preparation for different sizes of components was calculated and the volume of bone preserved by downsizing the cup was determined. Minimising medialisation of the acetabular component by 1–3 mm from the true floor was calculated. Absolute values and percentage of bone volume preserved when acetabular components are downsized or less medialised is presented. Downsizing the acetabular component by one size (2 mm) preserves between 2.6 cm 3 (size 40 vs 42) and 8.4 cm 3 (size 72 vs 74) of bone volume and consistently reduces resected bone volume by at least 35% (range 35.2%–37.5%). Similarly, reducing medialisation of a 56 mm acetabular cup (as an ex le of a commonly implanted component) by 3 mm reduces bone loss by 5.9 cm 3 – 44% less bone volume resection. Downsizing and minimising medialisation of the cup in THA substantially preserves bone which may benefit future revision surgeries. Surgeons could consider implanting the smallest acceptable acetabular shell to preserve bone without compromising on head size.
Publisher: Hindawi Limited
Date: 12-07-2016
DOI: 10.1002/TERM.2190
Abstract: Blood clots (haematomas) that form immediately following a bone fracture have been shown to be vital for the subsequent healing process. During the clotting process, a number of factors can influence the fibrin clot structure, such as fibrin polymerization, growth factor binding, cellular infiltration (including platelet retraction), protein concentrations and cytokines. The modulation of the fibrin clot structure within the fracture site has important clinical implications and could result in the development of multifunctional scaffolds that mimic the natural structure of a haematoma. Artificial haematoma structures such as these can be created from the patient's own blood and can therefore act as an ideal bone defect filling material for potential clinical application to accelerate bone regeneration. Copyright © 2016 John Wiley & Sons, Ltd.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 03-2006
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1016/J.ARTHRO.2005.03.004
Abstract: To determine whether a cone-shaped interference screw positioned centrally during tibial fixation in hamstring anterior cruciate ligament (ACL) reconstruction was equal to or better than a peripheral position in terms of stiffness, yield load, ultimate load, and mode of failure. Randomized matched-pair biomechanical pullout study. One of each of 7 matched pairs of human cadaveric tendon in porcine tibia with titanium cone-shaped screws were randomly allocated to either the peripheral or central group. Bone tunnels were drilled 45 degrees to the long axis of the tibia, akin to standard ACL reconstruction. Tunnel diameter was matched to tendon diameter and a screw 1 mm larger than tunnel diameter was inserted. A Universal Materials Testing Machine (Hounsfield Testing Equipment, Horsham, PA) was used to pull in the line of the tendon. Tendons were inspected after construct disassembly. The central screw configuration showed significantly higher stiffness (P = .0085), yield load (P = .0135), and ultimate load (P = .0075). The mode of failure in the peripheral screw position was slippage at the screw-tendon interface in all cases. In the central group, 87.5% of cases had a breakage in the tendon and 12.5% had slippage at the tendon-bone interface. Central interference screw fixation of soft-tissue ACL reconstruction offers superior fixation strength and stiffness in single pullout mode when compared with peripheral interference screw fixation. Failure in the central group was mostly by tendon breakage, suggesting that a larger difference may be exhibited by the central over the peripheral fixation than demonstrated in this study. Central interference screw fixation compared with peripheral fixation may allow greater confidence in early rehabilitation and reduced clinical failure rates in the long term.
Publisher: Wiley
Date: 19-08-2009
DOI: 10.1002/JCB.22312
Abstract: This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence.
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
Start Date: 2006
End Date: 2006
Funder: Australian Research Council
View Funded ActivityStart Date: 2010
End Date: 2013
Funder: Australian Research Council
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: Australian Research Council
View Funded Activity