ORCID Profile
0000-0001-7937-4432
Current Organisations
Xi'an Jiaotong University
,
Queensland University of Technology (QUT)
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Publisher: Springer Netherlands
Date: 2013
Publisher: Elsevier BV
Date: 09-2013
Publisher: Springer Science and Business Media LLC
Date: 02-03-2017
Abstract: Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM) however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2012
DOI: 10.1038/NATURE11632
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.ACTBIO.2022.09.042
Abstract: Three Dimensional (3D) bioprinting is one of the most recent additive manufacturing technologies and enables the direct incorporation of cells within a highly porous 3D-bioprinted construct. While the field has mainly focused on developing methods for enhancing printing resolution and shape fidelity, little is understood about the biological impact of bioprinting on cells. To address this shortcoming, this study investigated the in vitro and in vivo response of human osteoblasts subsequent to bioprinting using gelatin methacryloyl (GelMA) as the hydrogel precursor. First, bioprinted and two-dimensional (2D) cultured osteoblasts were compared, demonstrating that the 3D microenvironment from bioprinting enhanced bone-related gene expression. Second, differentiation regimens of 2-week osteogenic pre-induction in 2D before bioprinting and/or 3-week post-printing osteogenic differentiation were assessed for their capacity to increase the bioprinted construct's biofunctionality towards bone regeneration. The combination of pre-and post-induction regimens showed superior osteogenic gene expression and mineralisation in vitro. Moreover, a rat calvarial model using microtomography and histology demonstrated bone regeneration potential for the pre-and post-differentiation procedure. This study shows the positive impact of bioprinting on cells for osteogenic differentiation and the increased in vivo osteogenic potential of bioprinted constructs via a pre-induction method. STATEMENT OF SIGNIFICANCE: 3D bioprinting, one of the most recent technologies for tissue engineering has mostly focussed on developing methods for enhancing printing properties, little is understood on the biological impact of bioprinting and /or subsequent in vitro maturation methods on cells. Therefore, we addressed these fundamental questions by investigating osteoblast gene expression in bioprinted construct and assessed the efficacy of several induction regimen towards osteogenic differentiation in vitro and in vivo. Osteogenic induction of cells prior to seeding in scaffolds used in conventional tissue engineering applications has been demonstrated to increase the osteogenic potential of the resulting construct. However, to the best of our knowledge, pre-induction methods have not been investigated in 3D bioprinting.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.BIOMATERIALS.2013.09.074
Abstract: Cell-based therapy is considered a promising approach to achieving predictable periodontal regeneration. In this study, the regenerative potential of cell sheets derived from different parts of the periodontium (gingival connective tissue, alveolar bone and periodontal ligament) were investigated in an athymic rat periodontal defect model. Periodontal ligament (PDLC), alveolar bone (ABC) and gingival margin-derived cells (GMC) were obtained from human donors. The osteogenic potential of the primary cultures was demonstrated in vitro. Cell sheets supported by a calcium phosphate coated melt electrospun polycaprolactone (CaP-PCL) scaffold were transplanted to denuded root surfaces in surgically created periodontal defects, and allowed to heal for 1 and 4 weeks. The CaP-PCL scaffold alone was able to promote alveolar bone formation within the defect after 4 weeks. The addition of ABC and PDLC sheets resulted in significant periodontal attachment formation. The GMC sheets did not promote periodontal regeneration on the root surface and inhibited bone formation within the CaP-PCL scaffold. In conclusion, the combination of either PDLC or ABC sheets with a CaP-PCL scaffold could promote periodontal regeneration, but ABC sheets were not as effective as PDLC sheets in promoting new attachment formation.
Publisher: Wiley
Date: 18-02-2017
DOI: 10.1111/JCPE.12686
Abstract: Alveolar bone regeneration remains a significant clinical challenge in periodontology and dental implantology. This study assessed the mineralized tissue forming potential of 3-D printed medical grade polycaprolactone (mPCL) constructs containing osteoblasts (OB) encapsulated in a hyaluronic acid (HA)-hydrogel incorporating bone morphogenetic protein-7 (BMP-7). HA-hydrogels containing human OB ± BMP-7 were prepared. Cell viability, osteogenic gene expression, mineralized tissue formation and BMP-7 release in vitro, were assessed by fluorescence staining, RT-PCR, histological/μ-CT examination and ELISA respectively. In an athymic rat model, subcutaneous ectopic mineralized tissue formation in mPCL-hydrogel constructs was assessed by μ-CT and histology. Osteoblast encapsulation in HA-hydrogels did not detrimentally effect cell viability, and 3-D culture in osteogenic media showed mineralized collagenous matrix formation after 6 weeks. BMP-7 release from the hydrogel was biphasic, sustained and increased osteogenic gene expression in vitro. After 4 weeks in vivo, mPCL-hydrogel constructs containing BMP-7 formed significantly more volume (mm Functionalized mPCL-HA hydrogel constructs provide a favourable environment for bone tissue engineering. Although encapsulated cells contributed to mineralized tissue formation within the hydrogel in vitro and in vivo, their addition did not result in an improved outcome compared to BMP-7 alone.
Publisher: Springer Science and Business Media LLC
Date: 29-07-2016
Publisher: American Association for the Advancement of Science (AAAS)
Date: 17-02-2012
Abstract: Identifying genes that give rise to diseases is one of the major goals of sequencing human genomes. However, putative loss-of-function genes, which are often some of the first identified targets of genome and exome sequencing, have often turned out to be sequencing errors rather than true genetic variants. In order to identify the true scope of loss-of-function genes within the human genome, MacArthur et al. (p. 823 see the Perspective by Quintana-Murci ) extensively validated the genomes from the 1000 Genomes Project, as well as an additional European in idual, and found that the average person has about 100 true loss-of-function alleles of which approximately 20 have two copies within an in idual. Because many known disease-causing genes were identified in “normal” in iduals, the process of clinical sequencing needs to reassess how to identify likely causative alleles.
Publisher: American Chemical Society (ACS)
Date: 27-10-2011
DOI: 10.1021/BM201291E
Abstract: A series of copolymers of trimethylene carbonate (TMC) and L-lactide (LLA) were synthesized and evaluated as scaffolds for the production of artificial blood vessels. The polymers were end-functionalized with acrylate, cast into films, and cross-linked using UV light. The mechanical, degradation, and biocompatibility properties were evaluated. High TMC polymers showed mechanical properties comparable to human arteries (Young's moduli of 1.2-1.8 MPa and high elasticity with repeated cycling at 10% strain). Over 84 days degradation in PBS, the modulus and material strength decreased gradually. The polymers were nontoxic and showed good cell adhesion and proliferation over 7 days using human mesenchymal stem cells. When implanted into the rat peritoneal cavity, the polymers elicited formation of tissue capsules composed of myofibroblasts, resembling immature vascular smooth muscle cells. Thus, these polymers showed properties which were tunable and favorable for vascular tissue engineering, specifically, the growth of artificial blood vessels in vivo.
Publisher: SAGE Publications
Date: 06-02-2018
Abstract: Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.JHSA.2017.06.014
Abstract: The field of hand surgery is constantly evolving to meet the challenges of repairing intricate anatomical structures with limited availability of donor tissue. The past 10 years have seen an exponential growth in tissue engineering, which has broadened the perspectives of tackling these age-old problems. Various fabrication techniques such as melt electrospinning and fused deposition modelling have been employed to synthesize 3-dimensional bioscaffolds that can be used to replace lost tissue. These bioscaffolds with strategic biomimicry have been shown to allow for integrative and functional repair of tissue injuries. This review article summarizes the most current advances in tissue engineering and its applications in the field of hand surgery. It outlines the current tissue engineering techniques commonly used for tackling musculoskeletal problems and highlights the most promising approaches according to clinical evidence. In particular, the paper explores regenerative medicine concepts applied to specific tissues including nerve, bone, cartilage, tendon, ligament, and vessels. In the face of innovative and pioneering research, tissue engineering will undoubtedly play a key role in reconstructive hand surgery in the not too distant future.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7TB00165G
Abstract: Precise interface engineering in inorganic–organic hybrid materials enhances both the elastic moduli and toughness of a biodegradable composite, which is of relevance for load-bearing applications in bone tissue engineering.
Publisher: Springer Science and Business Media LLC
Date: 11-12-1994
DOI: 10.1038/NATURE15393
Publisher: Elsevier BV
Date: 2008
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.ACTBIO.2012.08.015
Abstract: One limitation of electrospinning stems from the charge build-up that occurs during processing, preventing further fibre deposition and limiting the scaffold overall thickness and hence their end-use in tissue engineering applications targeting large tissue defect repair. To overcome this, we have developed a technique in which thermally induced phase separation (TIPS) and electrospinning are combined. Thick three-dimensional, multilayered composite scaffolds were produced by simply stacking in idual polycaprolactone (PCL) microfibrous electrospun discs into a cylindrical holder that was filled with a 3% poly(lactic-co-glycolic acid) (PLGA) solution in dimethylsulfoxide (a good solvent for PLGA but a poor one for PCL). The construct was quenched in liquid nitrogen and the solvent removed by leaching out in cold water. This technique enables the fabrication of scaffolds composed principally of electrospun membranes that have no limit to their thickness. The mechanical properties of these scaffolds were assessed under both quasi-static and dynamic conditions. The multilayered composite scaffolds had similar compressive properties to 5% PCL scaffolds fabricated solely by the TIPS methodology. However, tensile tests demonstrated that the multilayered construct outperformed a scaffold made purely by TIPS, highlighting the contribution of the electrospun component of the composite scaffold to enhancing the overall mechanical property slate. Cell studies revealed cell infiltration principally from the scaffold edges under static seeding conditions. This fabrication methodology permits the rapid construction of thick, strong scaffolds from a range of biodegradable polymers often used in tissue engineering, and will be particularly useful when large dimension electrospun scaffolds are required.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.ARCHORALBIO.2018.01.014
Abstract: Decellularization aims to harness the regenerative properties of native extracellular matrix. The objective of this study was to evaluate different methods of decellularization of periodontal ligament cell sheets whilst maintaining their structural and biological integrity. Human periodontal ligament cell sheets were placed onto melt electrospun polycaprolactone (PCL) membranes that reinforced the cell sheets during the various decellularization protocols. These cell sheet constructs (CSCs) were decellularized under static erfusion conditions using a) 20 mM ammonium hydroxide (NH4OH)/Triton X-100, 0.5% v/v and b) sodium dodecyl sulfate (SDS, 0.2% v/v), both +/- DNase besides Freeze-thaw (F/T) cycling method. CSCs were assessed using a collagen quantification assay, immunostaining and scanning electron microscopy. Residual fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were assessed with Bio-plex assays. DNA removal without DNase was higher under static conditions. However, after DNase treatment, there were no differences between the different decellularization methods with virtually 100% DNA removal. DNA elimination in F/T was less efficient even after DNase treatment. Collagen content was preserved with all techniques, except with SDS treatment. Structural integrity was preserved after NH4OH/Triton X-100 and F/T treatment, while SDS altered the extracellular matrix structure. Growth factor amounts were reduced after decellularization with all methods, with the greatest reduction (to virtually undetectable amounts) following SDS treatment, while NH4OH/Triton X-100 and DNase treatment resulted in approximately 10% retention. This study showed that treatment with NH4OH/Triton X-100 and DNase solution was the most efficient method for DNA removal and the preservation of extracellular matrix integrity and growth factors retention.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.BIOMATERIALS.2013.03.088
Abstract: This study investigated the effect of a calcium phosphate (CaP) coating onto a polycaprolactone melt electrospun scaffold and in vitro culture conditions on ectopic bone formation in a subcutaneous rat model. The CaP coating resulted in an increased alkaline phosphatase activity (ALP) in ovine osteoblasts regardless of the culture conditions and this was also translated into higher levels of mineralisation. A subcutaneous implantation was performed and increasing ectopic bone formation was observed over time for the CaP-coated s les previously cultured in osteogenic media whereas the corresponding non-coated s les displayed a lag phase before bone formation occurred from 4 to 8 weeks post-implantation. Histology and immunohistochemistry revealed bone fill through the scaffolds 8 weeks post-implantation for coated and non-coated specimens and that ALP, osteocalcin and collagen 1 were present at the ossification front and in the bone tissues. Vascularisation in the vicinity of the bone tissues was also observed indicating that the newly formed bone was not deprived of oxygen and nutrients. We found that in vitro osteogenic induction was essential for achieving bone formation and CaP coating accelerated the osteogenic process. We conclude that high cell density and preservation of the collagenous and mineralised extracellular matrix secreted in vitro are factors of importance for ectopic bone formation.
Publisher: Wiley
Date: 20-12-2008
DOI: 10.1002/JBM.B.30982
Abstract: Scaffolding is an essential issue in tissue engineering and scaffolds should answer certain essential criteria: biocompatibility, high porosity, and important pore interconnectivity to facilitate cell migration and fluid diffusion. In this work, a modified solvent casting-particulate leaching out method is presented to produce scaffolds with spherical and interconnected pores. Sugar particles (200-300 microm and 300-500 microm) were poured through a horizontal Meker burner flame and collected below the flame. While crossing the high temperature zone, the particles melted and adopted a spherical shape. Spherical particles were compressed in plastic mold. Then, poly-L-lactic acid solution was cast in the sugar assembly. After solvent evaporation, the sugar was removed by immersing the structure into distilled water for 3 days. The obtained scaffolds presented highly spherical interconnected pores, with interconnection pathways from 10 to 100 mum. Pore interconnection was obtained without any additional step. Compression tests were carried out to evaluate the scaffold mechanical performances. Moreover, rabbit bone marrow mesenchymal stem cells were found to adhere and to proliferate in vitro in the scaffold over 21 days. This technique produced scaffold with highly spherical and interconnected pores without the use of additional organic solvents to leach out the porogen.
Publisher: MDPI AG
Date: 19-02-2014
DOI: 10.3390/PR2010167
Publisher: American Vacuum Society
Date: 11-2020
DOI: 10.1116/6.0000687
Abstract: Surface modification of biomaterials is a strategy used to improve cellular and in vivo outcomes. However, most studies do not evaluate the lifetime of the introduced surface layer, which is an important aspect affecting how a biomaterial will interact with a cellular environment both in the short and in the long term. This study evaluated the surface layer stability in vitro in buffer solution of materials produced from poly(lactic-co-glycolic acid) (50:50) and polycaprolactone modified by hydrolysis and/or grafting of hydrophilic polymers using grafting from approaches. The data presented in this study highlight the shortcomings of using model substrates (e.g., spun-coated films) rather than disks, particles, and scaffolds. It also illustrates how similar surface modification strategies in some cases result in very different lifetimes of the surface layer, thus emphasizing the need for these studies as analogies cannot always be drawn.
Publisher: American Vacuum Society
Date: 09-02-2012
DOI: 10.1007/S13758-011-0013-7
Abstract: Flexible tubular structures fabricated from solution electrospun fibers are finding increasing use in tissue engineering applications. However it is difficult to control the deposition of fibers due to the chaotic nature of the solution electrospinning jet. By using non-conductive polymer melts instead of polymer solutions the path and collection of the fiber becomes predictable. In this work we demonstrate the melt electrospinning of polycaprolactone in a direct writing mode onto a rotating cylinder. This allows the design and fabrication of tubes using 20 μm diameter fibers with controllable micropatterns and mechanical properties. A key design parameter is the fiber winding angle, where it allows control over scaffold pore morphology (e.g. size, shape, number and porosity). Furthermore, the establishment of a finite element model as a predictive design tool is validated against mechanical testing results of melt electrospun tubes to show that a lesser winding angle provides improved mechanical response to uniaxial tension and compression. In addition, we show that melt electrospun tubes support the growth of three different cell types in vitro and are therefore promising scaffolds for tissue engineering applications.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.ACTBIO.2013.02.009
Abstract: The growth of suitable tissue to replace natural blood vessels requires a degradable scaffold material that is processable into porous structures with appropriate mechanical and cell growth properties. This study investigates the fabrication of degradable, crosslinkable prepolymers of l-lactide-co-trimethylene carbonate into porous scaffolds by electrospinning. After crosslinking by γ-radiation, dimensionally stable scaffolds were obtained with up to 56% trimethylene carbonate incorporation. The fibrous mats showed Young's moduli closely matching human arteries (0.4-0.8MPa). Repeated cyclic extension yielded negligible change in mechanical properties, demonstrating the potential for use under dynamic physiological conditions. The scaffolds remained elastic and resilient at 30% strain after 84days of degradation in phosphate buffer, while the modulus and ultimate stress and strain progressively decreased. The electrospun mats are mechanically superior to solid films of the same materials. In vitro, human mesenchymal stem cells adhered to and readily proliferated on the three-dimensional fiber network, demonstrating that these polymers may find use in growing artificial blood vessels in vivo.
Publisher: Springer New York
Date: 07-12-2016
DOI: 10.1007/978-1-4939-6685-1_23
Abstract: Decellularized tissue-engineered constructs have the potential to promote regeneration by providing a biomimetic extracellular matrix that directs tissue-specific regeneration when implanted in situ. Recently, the use of cell sheets has shown promising results in promoting periodontal regeneration. Here, we describe the fabrication of decellularized periodontal cell sheets with intact extracellular matrix structural and biological properties. Melt electro spun polycaprolactone (PCL) scaffolds are used as a carrier for the inherently fragile cell sheets, to provide support during the processes of decellularization. An optimized decellularization method is outlined using perfusion with a combination of NH
Publisher: SAGE Publications
Date: 29-06-2015
Abstract: Craniofacial tissues are organized with complex 3-dimensional (3D) architectures. Mimicking such 3D complexity and the multicellular interactions naturally occurring in craniofacial structures represents one of the greatest challenges in regenerative dentistry. Three-dimensional bioprinting of tissues and biological structures has been proposed as a promising alternative to address some of these key challenges. It enables precise manufacture of various biomaterials with complex 3D architectures, while being compatible with multiple cell sources and being customizable to patient-specific needs. This review describes different 3D bioprinting methods and summarizes how different classes of biomaterials (polymer hydrogels, ceramics, composites, and cell aggregates) may be used for 3D biomanufacturing of scaffolds, as well as craniofacial tissue analogs. While the fabrication of scaffolds upon which cells attach, migrate, and proliferate is already in use, printing of all the components that form a tissue (living cells and matrix materials together) to produce tissue constructs is still in its early stages. In summary, this review seeks to highlight some of the key advantages of 3D bioprinting technology for the regeneration of craniofacial structures. Additionally, it stimulates progress on the development of strategies that will promote the translation of craniofacial tissue engineering from the laboratory bench to the chair side.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.BIOMATERIALS.2012.04.038
Abstract: This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum.
Publisher: Wiley
Date: 05-02-2014
DOI: 10.1111/JCPE.12214
Abstract: This study investigated the ability of an osteoconductive biphasic scaffold to simultaneously regenerate alveolar bone, periodontal ligament and cementum. A biphasic scaffold was built by attaching a fused deposition modelled bone compartment to a melt electrospun periodontal compartment. The bone compartment was coated with a calcium phosphate (CaP) layer for increasing osteoconductivity, seeded with osteoblasts and cultured in vitro for 6 weeks. The resulting constructs were then complemented with the placement of PDL cell sheets on the periodontal compartment, attached to a dentin block and subcutaneously implanted into athymic rats for 8 weeks. Scanning electron microscopy, X-ray diffraction, alkaline phosphatase and DNA content quantification, confocal laser microscopy, micro computerized tomography and histological analysis were employed to evaluate the scaffold's performance. The in vitro study showed that alkaline phosphatase activity was significantly increased in the CaP-coated s les and they also displayed enhanced mineralization. In the in vivo study, significantly more bone formation was observed in the coated scaffolds. Histological analysis revealed that the large pore size of the periodontal compartment permitted vascularization of the cell sheets, and periodontal attachment was achieved at the dentin interface. This work demonstrates that the combination of cell sheet technology together with an osteoconductive biphasic scaffold could be utilized to address the limitations of current periodontal regeneration techniques.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.ACTBIO.2022.07.023
Abstract: Periodontal regeneration is characterized by the attachment of oblique periodontal ligament fibres on the tooth root surface. To facilitate periodontal ligament attachment, a fibre-guiding tissue engineered biphasic construct was manufactured by melt electrowriting (MEW) for influencing reproducible cell guidance and tissue orientation. The biphasic scaffold contained fibre-guiding features in the periodontal ligament component comprising of 100 µm spaced channels (100CH), a pore size gradient in the bone component and maintained a highly porous and fully interconnected interface between the compartments. The efficacy of the fibre-guiding channels was assessed in an ectopic periodontal attachment model in immunocompromised rats. This demonstrated an unprecedented and systematic tissue alignment perpendicular to the dentin in the 100CH group, resulting in the close mimicry of native periodontal ligament architecture. In addition, the histology revealed high levels of tissue integration between the two compartments as observed by the perpendicular collagen attachment on the dentin surface, which also extended and infiltrated the scaffold's bone compartment. In conclusion, the 100 µm fibre-guiding scaffold induced a systematic tissue orientation at the dentin-ligament interface, resembling the native periodontium and thus resulting in enhanced alignment mimicking periodontal ligament regeneration. STATEMENT OF SIGNIFICANCE: Periodontitis is a prevalent inflammatory disease affecting a large portion of the adult population and leading to the destruction of the tooth-supporting structures (alveolar bone, periodontal ligament, and cementum). Current surgical treatments are unpredictable and generally result in repair rather than functional regeneration. A key feature of functional regeneration is the re-insertion of the oblique or perpendicularly orientated periodontal ligament fibre in both the alveolar bone and root surface. This study demonstrates that a highly porous scaffold featuring 100 µm width channels manufactured by the stacking of melt electrospun fibres, induced perpendicular alignment and attachment of the neo-ligament onto a dentine surface. The fibre guiding micro-architecture may pave the way for enhanced and more functional regeneration of the periodontium.
Publisher: Springer Science and Business Media LLC
Date: 30-11-2020
DOI: 10.1038/S41467-020-20128-W
Abstract: Correction to this paper has been published: 0.1038/s41467-020-20128-w
Publisher: Wiley
Date: 02-08-2010
DOI: 10.1002/JBM.A.32801
Abstract: We developed a novel technique involving knitting and electrospinning to fabricate a composite scaffold for ligament tissue engineering. Knitted structures were coated with poly(L-lactic-co-e-caprolactone) (PLCL) and then placed onto a rotating cylinder and a PLCL solution was electrospun onto the structure. Highly aligned 2-microm-diameter microfibers covered the space between the stitches and adhered to the knitted scaffolds. The stress-strain tensile curves exhibited an initial toe region similar to the tensile behavior of ligaments. Composite scaffolds had an elastic modulus (150 +/- 14 MPa) similar to the modulus of human ligaments. Biological evaluation showed that cells proliferated on the composite scaffolds and they spontaneously orientated along the direction of microfiber alignment. The microfiber architecture also induced a high level of extracellular matrix secretion, which was characterized by immunostaining. We found that cells produced collagen type I and type III, two main components found in ligaments. After 14 days of culture, collagen type III started to form a fibrous network. We fabricated a composite scaffold having the mechanical properties of the knitted structure and the morphological properties of the aligned microfibers. It is difficult to seed a highly macroporous structure with cells, however the technique we developed enabled an easy cell seeding due to presence of the microfiber layer. Therefore, these scaffolds presented attractive properties for a future use in bioreactors for ligament tissue engineering.
Publisher: Escola Bahiana de Medicina e Saude Publica
Date: 13-09-2023
Publisher: American Chemical Society (ACS)
Date: 21-04-2021
Publisher: Informa UK Limited
Date: 03-03-2008
Publisher: Wiley
Date: 05-03-2020
DOI: 10.1111/JRE.12729
Publisher: Springer Science and Business Media LLC
Date: 28-08-2020
DOI: 10.1038/S41467-020-17359-2
Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 09-07-0077
DOI: 10.1038/NATURE13385
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2BM00039C
Publisher: SAGE Publications
Date: 19-08-2014
Abstract: For a successful clinical outcome, periodontal regeneration requires the coordinated response of multiple soft and hard tissues (periodontal ligament, gingiva, cementum, and bone) during the wound-healing process. Tissue-engineered constructs for regeneration of the periodontium must be of a complex 3-dimensional shape and adequate size and demonstrate biomechanical stability over time. A critical requirement is the ability to promote the formation of functional periodontal attachment between regenerated alveolar bone, and newly formed cementum on the root surface. This review outlines the current advances in multiphasic scaffold fabrication and how these scaffolds can be combined with cell- and growth factor–based approaches to form tissue-engineered constructs capable of recapitulating the complex temporal and spatial wound-healing events that will lead to predictable periodontal regeneration. This can be achieved through a variety of approaches, with promising strategies characterized by the use of scaffolds that can deliver and stabilize cells capable of cementogenesis onto the root surface, provide biomechanical cues that encourage perpendicular alignment of periodontal fibers to the root surface, and provide osteogenic cues and appropriate space to facilitate bone regeneration. Progress on the development of multiphasic constructs for periodontal tissue engineering is in the early stages of development, and these constructs need to be tested in large animal models and, ultimately, human clinical trials.
Publisher: Wiley
Date: 26-02-2015
Abstract: The ability to test large arrays of cell and biomaterial combinations in 3D environments is still rather limited in the context of tissue engineering and regenerative medicine. This limitation can be generally addressed by employing highly automated and reproducible methodologies. This study reports on the development of a highly versatile and upscalable method based on additive manufacturing for the fabrication of arrays of scaffolds, which are enclosed into in idualized perfusion chambers. Devices containing eight scaffolds and their corresponding bioreactor chambers are simultaneously fabricated utilizing a dual extrusion additive manufacturing system. To demonstrate the versatility of the concept, the scaffolds, while enclosed into the device, are subsequently surface-coated with a biomimetic calcium phosphate layer by perfusion with simulated body fluid solution. 96 scaffolds are simultaneously seeded and cultured with human osteoblasts under highly controlled bidirectional perfusion dynamic conditions over 4 weeks. Both coated and noncoated resulting scaffolds show homogeneous cell distribution and high cell viability throughout the 4 weeks culture period and CaP-coated scaffolds result in a significantly increased cell number. The methodology developed in this work exemplifies the applicability of additive manufacturing as a tool for further automation of studies in the field of tissue engineering and regenerative medicine.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2020
DOI: 10.1038/S41586-020-1969-6
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale 1–3 . Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution in acral melanoma, for ex le, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter 4 identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation 5,6 analyses timings and patterns of tumour evolution 7 describes the erse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity 8,9 and evaluates a range of more-specialized features of cancer genomes 8,10–18 .
Publisher: American Chemical Society (ACS)
Date: 03-12-2020
Publisher: Springer Science and Business Media LLC
Date: 21-09-2020
DOI: 10.1038/S41467-020-18151-Y
Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA s les, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological ergences between two reproducible somatic variant detection efforts.
Publisher: Future Medicine Ltd
Date: 03-2015
DOI: 10.2217/NNM.14.218
Abstract: Aim: Topographically modified substrates are increasingly used in tissue engineering to enhance biomimicry. The overarching hypothesis is that topographical cues will control cellular response at the cell–substrate interface. Materials & methods: The influence of anisotropically ordered poly(lactic-co-glycolic acid) substrates (constant groove width of ˜1860 nm constant line width of ˜2220 nm variable groove depth of ˜35, 306 and 2046 nm) on in vitro and in vivo osteogenesis were assessed. Results & discussion: We demonstrate that substrates with groove depths of approximately 306 and 2046 nm promote osteoblast alignment parallel to underlined topography in vitro. However, none of the topographies assessed promoted directional osteogenesis in vivo. Conclusion: 2D imprinting technologies are useful tools for in vitro cell phenotype maintenance.
Publisher: Wiley
Date: 26-03-2015
DOI: 10.1002/PATH.4519
Abstract: Neurological heterotopic ossification (NHO) is the abnormal formation of bone in soft tissues as a consequence of spinal cord or traumatic brain injury. NHO causes pain, ankyloses, vascular and nerve compression and delays rehabilitation in this high-morbidity patient group. The pathological mechanisms leading to NHO remain unknown and consequently there are no therapeutic options to prevent or reduce NHO. Genetically modified mouse models of rare genetic forms of heterotopic ossification (HO) exist, but their relevance to NHO is questionable. Consequently, we developed the first model of spinal cord injury (SCI)-induced NHO in genetically unmodified mice. Formation of NHO, measured by micro-computed tomography, required the combination of both SCI and localized muscular inflammation. Our NHO model faithfully reproduced many clinical features of NHO in SCI patients and both human and mouse NHO tissues contained macrophages. Muscle-derived mesenchymal progenitors underwent osteoblast differentiation in vitro in response to serum from NHO mice without additional exogenous osteogenic stimuli. Substance P was identified as a candidate NHO systemic neuropeptide, as it was significantly elevated in the serum of NHO patients. However, antagonism of substance P receptor in our NHO model only modestly reduced the volume of NHO. In contrast, ablation of phagocytic macrophages with clodronate-loaded liposomes reduced the size of NHO by 90%, supporting the conclusion that NHO is highly dependent on inflammation and phagocytic macrophages in soft tissues. Overall, we have developed the first clinically relevant model of NHO and demonstrated that a combined insult of neurological injury and soft tissue inflammation drives NHO pathophysiology.
Publisher: American Chemical Society (ACS)
Date: 21-11-2019
Publisher: Springer Science and Business Media LLC
Date: 26-01-2012
DOI: 10.1007/S00441-011-1298-Z
Abstract: There is a growing need for successful bone tissue engineering strategies and advanced biomaterials that mimic the structure and function of native tissues carry great promise. Successful bone repair approaches may include an osteoconductive scaffold, osteoinductive growth factors, cells with an osteogenic potential and capacity for graft vascularisation. To increase osteoinductivity of biomaterials, the local combination and delivery of growth factors has been developed. In the present study we investigated the osteogenic effects of calcium phosphate (CaP)-coated nanofiber mesh tube-mediated delivery of BMP-7 from a PRP matrix for the regeneration of critical sized segmental bone defects in a small animal model. Bilateral full-thickness diaphyseal segmental defects were created in twelve male Lewis rats and nanofiber mesh tubes were placed around the defect. Defects received either treatment with a CaP-coated nanofiber mesh tube (n = 6), an un-coated nanofiber mesh tube (n=6) a CaP-coated nanofiber mesh tube with PRP (n=6) or a CaP-coated nanofiber mesh tube in combination with 5 μg BMP-7 and PRP (n = 6). After 12 weeks, bone volume and biomechanical properties were evaluated using radiography, microCT, biomechanical testing and histology. The results demonstrated significantly higher biomechanical properties and bone volume for the BMP group compared to the control groups. These results were supported by the histological evaluations, where BMP group showed the highest rate of bone regeneration within the defect. In conclusion, BMP-7 delivery via PRP enhanced functional bone defect regeneration, and together these data support the use of BMP-7 in the treatment of critical sized defects.
Publisher: Wiley
Date: 07-09-2020
DOI: 10.1002/JOR.24785
Abstract: Scapholunate interosseous ligament tears are a common wrist injury in young and active patients that can lead to suboptimal outcomes after repair. This research aims to assess a multiphasic scaffold using 3D‐printing for reconstruction of the dorsal scapholunate interosseous ligament. The scaffold was surgically implanted in vivo in the position of the native rabbit medial collateral ligament. Two branches of treatment were implemented in the study. In the first group, the rabbits (n = 8) had the knee joint fixed in flexion for 4 weeks using 1.4 mm K‐wires prior to s le harvesting. The second group (n = 8) had the rabbit knee joint immobilized for 4 weeks prior to K‐wire removal and mobilization for an additional 4 weeks prior to s le harvesting. Overall, s les were harvested at 4 weeks post‐surgery (immobilized group) and eight weeks post‐surgery (mobilized group). Mechanical tensile testing (n = 5/group) and histology (n = 3/group) of the constructs were conducted. Tissue integration and maturation were observed resulting in increased mechanical strength of the operated joint at 8 weeks ( P .05). Bone and ligament tissues were regenerated in their respective compartments with structural and mechanical properties approaching those reported for the human dorsal SLIL ligament. Clinical Significance: This proof of concept study has demonstrated that the synthetic multiphasic scaffold was capable of regenerating both bone and ligament while also withstanding the physiological load once implanted in the rabbit knee. The artificial scaffold may provide an alternative to current techniques for reconstruction of scapholunate instability or other ligament injuries in the hand and wrist.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.ACTBIO.2021.11.047
Abstract: Recent advances in the field of regenerative medicine and biomaterial science have highlighted the importance of controlling immune cell phenotypes at the biomaterial interface. These studies have clearly indicated that a rapid resolution of the inflammatory process, mediated by a switch in the macrophage population towards a reparative phenotype, is essential for tissue regeneration to occur. While various biomaterial surfaces have been developed in order to impart immunomodulatory properties to the resulting constructs, an alternative strategy involving the use of reparative biological cues, known as resolvins, is emerging in regenerative medicine. This review reports on the mechanisms via which resolvins participate in the resolution of inflammation and describes their current utilisation in pre-clinical and clinical settings, along with their effectiveness when combined with biomaterial constructs in tissue engineering applications. STATEMENT OF SIGNIFICANCE: The resolution of the inflammatory process is necessary for achieving tissue healing and regeneration. Resolvins are lipid mediators and play a key role in the resolution of the inflammatory response and can be used in as biological cues to promote tissue regeneration. This review describes the various biological inflammatory mechanisms and pathways involving resolvins and how their action results in a pro-healing response. The use of these molecules in the clinical setting is then summarised for various applications along with their limitations. Lastly, the review focuses on the emergence resolvins in tissue engineering products including the use of a more stable form which holds greater prospect for regenerative purposes.
Publisher: American Chemical Society (ACS)
Date: 17-07-2023
Publisher: Wiley
Date: 03-07-2015
DOI: 10.1111/CLR.12652
Abstract: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. Nine sheep underwent bilateral sinus augmentation. Each sinus was randomized to receive either control or test bone graft. Three animals were sacrificed at 8 weeks, and six animals were sacrificed at 16 weeks post-grafting. The 18 sinuses were processed for histomorphometry, which assessed the area fraction of new bone (%NB), residual graft (%RG) and soft tissue components (% STM), as well as graft particle osseointegration (% OI), within three zones equally distributed from the augmented sinus floor. At week 16, a significant increase in %NB was evident across all three zones in the control group when compared to week 8. A significantly greater %NB was evident in the control group when compared to the test group in zones 2 (P < 0.001) and 3 (P < 0.001). There was a significant increase in %OI in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %OI in the control group was significantly greater across all three zones when compared to the test group at week 16 (P < 0.001). Zone was found to be a significant main effect (P < 0.001) that was independent of time and treatment with decreasing %OI in distant zones. %RG did not significantly change with time for both groups. There was a significant reduction in %ST in week 16 when compared to week 8 across all three zones in the control group (P < 0.001). %ST in the test group was significantly greater across all zones when compared to the control group at week 16 (P < 0.001). Both groups exhibited very similar histomorphometric measurements in the zones proximal to the resident sinus wall. The % NB and % OI were greatest in the zones proximal to resident bony walls and gradually decreased as the distance from the proximal walls increased. There was greater % NB and % OI in the control group when compared to the test group in the distant zone.
Publisher: Wiley
Date: 16-09-2016
DOI: 10.1111/CLR.12694
Abstract: To histomorphometrically compare the use of collagen-stabilized anorganic bovine bone (ABBM-C) (test) to anorganic bovine bone + autogenous bone (ABBM + AB) (control) in maxillary sinus augmentation. Forty (n = 40 sinuses) patients underwent sinus augmentation and received either control (20 sinuses) or test bone graft (20 sinuses). Bone s les were harvested from the augmented sinuses 5 months postgrafting. The s les were processed for histomorphometry, which assessed within the primary region of interest (ROI-1), the area fraction of new bone (%NB), graft particle osseointegration (% OI), residual graft (%RG), and soft tissue components (% STM). The same analysis was also carried out in a second region of interest (ROI-2) located in a zone 1 mm proximal to the previous maxillary sinus floor. In both ROI-1 and ROI-2, the mean % NB, %RG, and %STM in the control group were similar to mean values in the test group. The % OI was significantly greater in the control group (42.0 +/- 26.8) when compared to the test group (19.6 +/- 27.3) in ROI-2 (P < 0.05). No statistically significant differences were seen when ROI-1 and ROI-2 were compared except for improved %OI in ROI-2 in the control group. The mean proportion of lamellar bone to woven bone in the control group (1.22 ± 1.48) was significantly greater than the test group (0.38 ± 0.29) (P < 0.05). ABBM-C exhibited very similar histomorphometric parameters to the composite graft of ABBM + AB. The ABBM + AB group was more mature as indicated by the significantly greater proportion of lamellar bone when compared to the ABBM-C. Improved % OI was seen in the zone proximal to the resident bony floor in the ABBM + AB group. Based on histological assessment, ABBM-C is a suitable bone substitute for the purposes of maxillary sinus augmentation. Its clinical utility may be indicated in cases of sinus membrane perforation and insufficient autogenous bone in the local area.
Publisher: SAGE Publications
Date: 10-04-2019
Abstract: This study reports on scaffold-based periodontal tissue engineering in a large preclinical animal model. A biphasic scaffold consisting of bone and periodontal ligament compartments manufactured by melt and solution electrospinning, respectively, was used for the delivery of in vitro matured cell sheets from 3 sources: gingival cells (GCs), bone marrow–derived mesenchymal stromal cells (Bm-MSCs), and periodontal ligament cells (PDLCs). The construct featured a 3-dimensional fibrous bone compartment with macroscopic pore size, while the periodontal compartment consisted of a flexible porous membrane for cell sheet delivery. The regenerative performance of the constructs was radiographically and histologically assessed in surgically created periodontal defects in sheep following 5 and 10 wk of healing. Histologic observation demonstrated that the constructs maintained their shape and volume throughout the entirety of the in vivo study and were well integrated with the surrounding tissue. There was also excellent tissue integration between the bone and periodontal ligament compartments as well as the tooth root interface, enabling the attachment of periodontal ligament fibers into newly formed cementum and bone. Bone coverage along the root surface increased between weeks 5 and 10 in the Bm-MSC and PDLC groups. At week 10, the micro–computed tomography results showed that the PDLC group had greater bone fill as compared with the empty scaffold, while the GC group had less bone than the 3 other groups (control, Bm-MSC, and PDLC). Periodontal regeneration, as measured by histologically verified new bone and cementum formation with obliquely inserted periodontal ligament fibers, increased between 5 and 10 wk for the empty, Bm-MSC, and PDLC groups, while the GC group was inferior to the Bm-MSC and PDLC groups at 10 wk. This study demonstrates that periodontal regeneration can be achieved via the utilization of a multiphasic construct, with Bm-MSCs and PDLCs obtaining superior results as compared with GC-derived cell sheets.
Publisher: Wiley
Date: 26-08-2018
Abstract: The periodontium, consisting of gingiva, periodontal ligament, cementum, and alveolar bone, is a hierarchically organized tissue whose primary role is to provide physical and mechanical support to the teeth. Severe cases of periodontitis, an inflammatory condition initiated by an oral bacterial biofilm, can lead to significant destruction of soft and hard tissues of the periodontium and result in compromised dental function and aesthetics. Although current treatment approaches can limit the progression of the disease by controlling the inflammatory aspect, complete periodontal regeneration cannot be predictably achieved. Various tissue engineering approaches are investigated for their ability to control the critical temporo-spatial wound healing events that are essential for achieving periodontal regeneration. This paper reviews recent progress in the field of periodontal tissue engineering with an emphasis on advanced 3D multiphasic tissue engineering constructs (TECs) and provides a critical analysis of their regenerative potential and limitations. The review also elaborates on the future of periodontal tissue engineering, including scaffold customization for in idual periodontal defects, TEC's functionalization strategies for imparting enhanced bioactivity, periodontal ligament fiber guidance, and the utilization of chair-side regenerative solutions that can facilitate clinical translation.
Publisher: Informa UK Limited
Date: 2010
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.MSEC.2018.06.071
Abstract: Vertical bone augmentation of the jaws is required when the height of bone is insufficient at the site of dental implant placement. In this proof of concept study, we investigated the potential of a biphasic polycaprolactone construct combined with a hyaluronic acid based hydrogel loaded with recombinant human bone morphogenetic growth factor-2 (BMP-2) for vertical bone regeneration. The biphasic scaffold consisted of an outer shell manufactured by fused deposition modelling, mimicking native cortical bone and providing mechanical and space maintenance properties essential for bone formation. Within this shell, a 90% porous melt electrospun microfibrous mesh mimicking the architecture of cancellous bone was incorporated in order to facilitate hydrogel loading and subsequent osteogenesis and angiogenesis. The in vitro performances of the biphasic construct demonstrated that BMP-2 was released in a sustained manner over several weeks and that cell viability was maintained in the hydrogel over 21 days. qRT-PCR demonstrated the upregulation of bone markers such as osteopontin, osteocalcin and collagen 1A1 at day 3 and 14 in the constructs loaded with BMP2. In vivo assessment of the biphasic scaffold was performed using a dose of 30 μg of BMP-2 in a rabbit calvarial vertical bone augmentation model. The histology and micro-CT analysis of the elevated space demonstrated that the hydrogel and the presence of BMP-2 enabled bone formation. However, this was limited to the immediate vicinity of the calvarial bone. The amount of newly formed bone was relatively small which was likely due to poor vascularisation of the extraskeletal space. The utilisation of this biomimetic biphasic construct with excellent space maintenance properties can be of interest in dentistry although the in vivo model requires refinement to demonstrated appropriate efficacy.
Publisher: Wiley
Date: 29-09-2016
DOI: 10.1111/CLR.12988
Abstract: To assess the impact of a hydrophilic implant surface (SLActive Four sheep underwent bilateral sinus augmentation. Each sinus received anorganic bovine bone mineral + autogenous bone (ABBM + AB). Sixteen implants were subsequently placed 12 weeks postgrafting with each sinus receiving a control (SLA There was a statistically significant increase in %BIC at week 4 compared to the week 2 animals in both test (P < 0.005) and control (P < 0.005) groups. There was a statistically significant greater %BIC around test implants when compared to control implants in both week 2 (P < 0.05) and week 4 animals (P < 0.05). Greater %WB (11.17% ±6.82) and %LB (11.06% ±3.67) were seen in the test implants when compared to the control implants independent of time. This was only statistically significant for %LB (P < 0.05). A statistically significant reduction of 16.78% (±6.19) in %ST was noted in test implants when compared to control implants (P < 0.05) independent of time. Both time and the use of hydrophilic implant surface had a positive impact on %BIC around implants placed into augmented maxillary sinuses. Hydrophilic implant surfaces also had a positive impact on surrounding tissue composition. Larger trials are needed to better assess and detect differences between these two surfaces in augmented maxillary sinuses.
Publisher: Wiley
Date: 02-12-2013
DOI: 10.1002/AR.22795
Abstract: Critical-sized osteochondral defects are clinically challenging, with limited treatment options available. By engineering osteochondral grafts using a patient's own cells and osteochondral scaffolds designed to facilitate cartilage and bone regeneration, osteochondral defects may be treated with less complications and better long-term clinical outcomes. Scaffolds can influence the development and structure of the engineered tissue, and there is an increased awareness that osteochondral tissue engineering concepts need to take the in vivo complexities into account in order to increase the likelihood of successful osteochondral tissue repair. The developing trend in osteochondral tissue engineering is the utilization of multiphasic scaffolds to recapitulate the multiphasic nature of the native tissue. Cartilage and bone have different structural, mechanical, and biochemical microenvironments. By designing osteochondral scaffolds with tissue-specific architecture, it may be possible to enhance osteochondral repair within shorter timeframe. While there are promising in vivo outcomes using multiphasic approaches, functional regeneration of osteochondral constructs still remains a challenge. In this review, we provide an overview of in vivo osteochondral repair studies that have taken place in the past three years, and define areas which needs improvement in future studies.
Publisher: Wiley
Date: 21-05-2019
Abstract: The scapholunate interosseous ligament (SLIL) is a frequently torn wrist ligament, and current surgical options for SLIL tears are suboptimal. This research aims to develop a novel multiphasic bone-ligament-bone scaffold (BLB) with a porous interface using 3D-printing and cell sheet technology for the reconstruction of the dorsal scapholunate interosseous ligament. The BLB comprises two bone compartments bridged by aligned polycaprolactone fibers mimicking the architecture of the native tissue. Mechanical testing of the BLBs shows their ability to withstand physiological forces. Combination of the BLB with human bone marrow mesenchymal stem cell sheet demonstrates that the harvesting did not compromise cell viability, while allowing homogeneous distribution in the ligament compartment. The BLBs are loaded with cell sheets and bone morphogenetic protein-2 in the ligament and bone compartment respectively prior to ectopic implantation into athymic rats. The histology demonstrates rapid tissue infiltration, high vascularization, and more importantly the maintenance of the compartmentalization as bone formation remains localized to the bone compartment despite the porous interface. The cells in the ligament compartment become preferentially aligned, and this proof-of-concept study demonstrates that the BLB can provide sufficient compartmentalization and fiber guiding properties necessary for the regeneration of the dorsal SLIL.
Publisher: Wiley
Date: 30-09-2014
Publisher: Springer Science and Business Media LLC
Date: 28-01-2012
DOI: 10.1007/S00441-011-1318-Z
Abstract: Electrospun scaffolds manufactured using conventional electrospinning configurations have an intrinsic thickness limitation, due to a charge build-up at the collector. To overcome this limitation, an electrostatic lens has been developed that, at the same relative rate of deposition, focuses the polymer jet onto a smaller area of the collector, resulting in the fabrication of thick scaffolds within a shorter period of time. We also observed that a longer deposition time (up to 13 h, without the intervention of the operator) could be achieved when the electrostatic lens was utilised, compared to 9–10 h with a conventional processing set-up and also showed that fibre fusion was less likely to occur in the modified method. This had a significant impact on the mechanical properties, as the scaffolds obtained with the conventional process had a higher elastic modulus and ultimate stress and strain at short times. However, as the thickness of the scaffolds produced by the conventional electrospinning process increased, a 3-fold decrease in the mechanical properties was observed. This was in contrast to the modified method, which showed a continual increase in mechanical properties, with the properties of the scaffold finally having similar mechanical properties to the scaffolds obtained via the conventional process at longer times. This “focusing” device thus enabled the fabrication of thicker 3-dimensional electrospun scaffolds (of thicknesses up to 3.5 mm), representing an important step towards the production of scaffolds for tissue engineering large defect sites in a multitude of tissues.
Publisher: Wiley
Date: 07-02-2017
DOI: 10.1002/JBM.B.33828
Abstract: Ligament tissue rupture is a common sport injury. Although current treatment modalities can achieve appropriate reconstruction of the damaged ligament, they present significant drawbacks, mostly related to reduced tissue availability and pain associated with tissue harvesting. Stem cell based tissue regeneration combined with electrospun scaffolds represents a novel treatment method for torn ligaments. In this study, a low fiber density polycaprolactone (PCL) electrospun mesh and sheep mesenchymal stem cells (sMSCs) were used to develop tissue engineered ligament construct (TELC) in vitro. The assembly of the TELC was based on the spontaneous capacity of the cells to organize themselves into a cell sheet once seeded onto the electrospun mesh. The cell sheet matured over 4 weeks and strongly integrated with the low fiber density electrospun mesh which was subsequently processed into a ligament-like bundle and braided with two other bundles to develop the final construct. Live/dead assay revealed that the handling of the construct through the various phases of assembly did not cause significant difference in viability compared to the control. Mechanical evaluation demonstrated that the incorporation of the cell sheet into the braided construct resulted in significantly modifying the mechanical behavior. A stress/displacement J-curve was observed for the TELC that was similar to native ligament, whereas this particular feature was not observed in the non-cellularized specimens. The regenerative potential of the TELC was evaluated ectopically in immunocompromized rats, compared to non cellularized electrospun fiber mesh and this demonstrated that the TELC was well colonized by host cells and that a significant remodelling of the implanted construct was observed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 399-409, 2018.
Publisher: Wiley
Date: 12-06-2019
DOI: 10.1111/JRE.12664
Abstract: To evaluate the influence of systemic zoledronate administration on the osseointegration of titanium implants with different surface topography in rat maxillae. Twenty Sprague-Dawley rats were ided into two groups-test (bisphosphonate) and control (healthy). Bisphosphonate administration began three weeks prior to implant placement, and the animals received zoledronate (66 μg/kg) three times per week. Forty endosseous implants with a moderately rough (20 implants) or a turned surface (20 implants) were immediately placed bilaterally into extraction sockets of maxillary first molars. Animals were sacrificed after 14 and 28 days of healing, and en bloc specimens were harvested for histological and histomorphometric analysis. Osseointegration was quantified by measuring the percentage of bone-to-implant contact. Bone-to-implant contact (BIC) (mean ± SD) values of moderately rough and turned implants at day 14 in test group were 17.62 ± 6.68 and 10.69 ± 1.48, respectively, while in the control group, they were 46.36 ± 5.08 and 33.29 ± 8.89, respectively. At day 28, BIC values of moderately rough and turned implants in the test group were 25.94 ± 7.87 and 7.83 ± 4.30, respectively, while in the control group, they were 72.99 ± 6.60 and 47.62 ± 18.19, respectively. Statistically significant higher BIC values were measured on moderately rough implants compared to turned implants at 28 days, and the control group compared to the test group for both implant surfaces. Histological observations for the control and the test groups demonstrated initial bone formation around moderately rough implants not only on the surface of the parent bone, as was the case with the turned surfaced implants, but also along the implant surface itself. Systemic zoledronate administration negatively influences osseointegration. Osseointegration was enhanced adjacent to moderately rough compared to turned implants in both the presence and absence of systemic zoledronate administration. Therefore, topographical surface modification may partially offset the negative impact of zoledronate administration.
Publisher: IOP Publishing
Date: 08-05-2014
DOI: 10.1088/1758-5082/6/3/035006
Abstract: This study reports on an original concept of additive manufacturing for the fabrication of tissue engineered constructs (TEC), offering the possibility of concomitantly manufacturing a customized scaffold and a bioreactor chamber to any size and shape. As a proof of concept towards the development of anatomically relevant TECs, this concept was utilized for the design and fabrication of a highly porous sheep tibia scaffold around which a bioreactor chamber of similar shape was simultaneously built. The morphology of the bioreactor/scaffold device was investigated by micro-computed tomography and scanning electron microscopy confirming the porous architecture of the sheep tibiae as opposed to the non-porous nature of the bioreactor chamber. Additionally, this study demonstrates that both the shape, as well as the inner architecture of the device can significantly impact the perfusion of fluid within the scaffold architecture. Indeed, fluid flow modelling revealed that this was of significant importance for controlling the nutrition flow pattern within the scaffold and the bioreactor chamber, avoiding the formation of stagnant flow regions detrimental for in vitro tissue development. The bioreactor/scaffold device was dynamically seeded with human primary osteoblasts and cultured under bi-directional perfusion for two and six weeks. Primary human osteoblasts were observed homogenously distributed throughout the scaffold, and were viable for the six week culture period. This work demonstrates a novel application for additive manufacturing in the development of scaffolds and bioreactors. Given the intrinsic flexibility of the additive manufacturing technology platform developed, more complex culture systems can be fabricated which would contribute to the advances in customized and patient-specific tissue engineering strategies for a wide range of applications.
Publisher: The Royal Society
Date: 06-06-2014
Abstract: In vivo osteochondral defect models predominantly consist of small animals, such as rabbits. Although they have an advantage of low cost and manageability, their joints are smaller and more easily healed compared with larger animals or humans. We hypothesized that osteochondral cores from large animals can be implanted subcutaneously in rats to create an ectopic osteochondral defect model for routine and high-throughput screening of multiphasic scaffold designs and/or tissue-engineered constructs (TECs). Bovine osteochondral plugs with 4 mm diameter osteochondral defect were fitted with novel multiphasic osteochondral grafts composed of chondrocyte-seeded alginate gels and osteoblast-seeded polycaprolactone scaffolds, prior to being implanted in rats subcutaneously with bone morphogenic protein-7. After 12 weeks of in vivo implantation, histological and micro-computed tomography analyses demonstrated that TECs are susceptible to mineralization. Additionally, there was limited bone formation in the scaffold. These results suggest that the current model requires optimization to facilitate robust bone regeneration and vascular infiltration into the defect site. Taken together, this study provides a proof-of-concept for a high-throughput osteochondral defect model. With further optimization, the presented hybrid in vivo model may address the growing need for a cost-effective way to screen osteochondral repair strategies before moving to large animal preclinical trials.
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.ACTBIO.2011.02.036
Abstract: This study investigates the use of patterned collectors to increase the pore size of electrospun scaffolds for enhanced cell infiltration. The morphology of the patterned scaffolds was investigated by scanning electron microscopy, which showed that the collector pattern was accurately mimicked by the electrospun fibres. We observed an enlargement in the pore size and in the pore size distribution compared with conventional electrospinning. Mechanical testing revealed that the mechanical properties could be tailored, to some extent, according to the patterning and that the patterned scaffolds were softer than standard electrospun scaffolds. When NIH 3T3 fibroblasts were seeded onto patterned collectors improved cell infiltration was observed. Cells were able to penetrate up to 250 μm into the scaffolds, compared with 30 μm for the standard scaffolds. This increase in the depth of infiltration occurred as early as 24 h post-seeding and remained constant over 7 days.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Cedryck Vaquette.