ORCID Profile
0000-0002-9241-7676
Current Organisations
Universitair Medisch Centrum Utrecht
,
Universiteit Utrecht
,
University Medical Center Utrecht
,
Utrecht University
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Biomaterials | Applied Mathematics | Orthopaedics | Biomedical Engineering | Cellular Interactions (Incl. Adhesion, Matrix, Cell Wall) | Materials Engineering | Biological Mathematics | Polymers | Medical Biotechnology |
Skin and related disorders | Skeletal system and disorders (incl. arthritis) | Treatments (e.g. chemicals, antibiotics) | Surgical methods and procedures
Publisher: Wiley
Date: 11-2020
Publisher: IOP Publishing
Date: 22-07-2015
DOI: 10.1088/1758-5090/7/3/032001
Abstract: Auricular malformations, which impose a significant social and psychological burden, are currently treated using ear prostheses, synthetic implants or autologous implants derived from rib cartilage. Advances in the field of regenerative medicine and biofabrication provide the possibility to engineer functional cartilage with intricate architectures and complex shapes using patient-derived or donor cells. However, the development of a successful auricular cartilage implant still faces a number of challenges. These challenges include the generation of a functional biochemical matrix, the fabrication of a customized anatomical shape, and maintenance of that shape. Biofabrication technologies may have the potential to overcome these challenges due to their ability to reproducibly deposit multiple materials in complex geometries in a highly controllable manner. This topical review summarizes this potential of biofabrication technologies for the generation of implants for auricular reconstruction. In particular, it aims to discuss how biofabrication technologies, although still in pre-clinical phase, could overcome the challenges of generating and maintaining the desired auricular shapes. Finally, remaining bottlenecks and future directions are discussed.
Publisher: Elsevier BV
Date: 05-2016
Publisher: Springer Science and Business Media LLC
Date: 29-07-2016
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.JOCA.2019.06.009
Abstract: To investigate the potential of quantitative susceptibility mapping (QSM) and T2* relaxation time mapping to determine mechanical and structural properties of articular cartilage via univariate and multivariate analysis. S les were obtained from a cartilage repair study, in which surgically induced full-thickness chondral defects in the stifle joints of seven Shetland ponies caused post-traumatic osteoarthritis (14 s les). Control s les were collected from non-operated joints of three animals (6 s les). Magnetic resonance imaging (MRI) was performed at 9.4 T, using a 3-D multi-echo gradient echo sequence. Biomechanical testing, digital densitometry (DD) and polarized light microscopy (PLM) were utilized as reference methods. To compare MRI parameters with reference parameters (equilibrium and dynamic moduli, proteoglycan content, collagen fiber angle and -anisotropy), depth-wise profiles of MRI parameters were acquired at the biomechanical testing locations. Partial least squares regression (PLSR) and Spearman's rank correlation were utilized in data analysis. PLSR indicated a moderate-to-strong correlation (ρ = 0.49-0.66) and a moderate correlation (ρ = 0.41-0.55) between the reference values and T2* relaxation time and QSM profiles, respectively (excluding superficial-only results). PLSR correlations were noticeably higher than direct correlations between bulk MRI and reference parameters. 3-D parametric surface maps revealed spatial variations in the MRI parameters between experimental and control groups. Quantitative parameters from 3-D multi-echo gradient echo MRI can be utilized to predict the properties of articular cartilage. With PLSR, especially the T2* relaxation time profile appeared to correlate with the properties of cartilage. Furthermore, the results suggest that degeneration affects the QSM-contrast in the cartilage. However, this change in contrast is not easy to quantify.
Publisher: Wiley
Date: 18-02-2013
Abstract: Gelatin-methacrylamide (gelMA) hydrogels are shown to support chondrocyte viability and differentiation and give wide ranging mechanical properties depending on several cross-linking parameters. Polymer concentration, UV exposure time, and thermal gelation prior to UV exposure allow for control over hydrogel stiffness and swelling properties. GelMA solutions have a low viscosity at 37 °C, which is incompatible with most biofabrication approaches. However, incorporation of hyaluronic acid (HA) and/or co-deposition with thermoplastics allows gelMA to be used in biofabrication processes. These attributes may allow engineered constructs to match the natural functional variations in cartilage mechanical and geometrical properties.
Publisher: IOP Publishing
Date: 19-07-2016
Publisher: IOP Publishing
Date: 19-07-2016
Publisher: Wiley
Date: 19-02-2009
DOI: 10.1002/JBM.A.31864
Abstract: Skin cells for transplantation are routinely prepared by growing patient keratinocytes in a semi-defined cocktail of growth factors, including serum and feeder cells. However, these reagents require substantial risk remediation and can contribute to transplant rejection. Microcarrier culture is an emerging technology that may allow the elimination of feeder cells whilst facilitating expansion of cultured keratinocytes. However, the behavior of keratinocytes in microcarrier culture and the potential of these cells to form an epidermis have been poorly defined. We characterized freshly isolated human keratinocytes cultured on CultiSpher-G microcarriers in the absence of murine feeder cells and assessed the potential of the keratinocytes to form an epidermis in an in vitro model. In a single passage, keratinocytes multiplied 44.9-fold in microcarrier-bioreactor culture in 17 days, whereas two-dimensional cultures reached confluence in 9 days and only expanded 7.4-fold. Histological characterization of keratinocytes on the microcarriers revealed that the cells were randomly distributed within these porous structures, however, not all pores contained cells. High-resolution microcomputed tomography imaging of the microcarriers confirmed limited interconnectivity of the pores. Immunoreactivity of specific epidermal markers was confirmed during cell expansion via immunohistochemistry. Despite the expression of differentiation markers, microcarrier-expanded keratinocytes retained the capacity to form an epidermis, as was evaluated using an in vitro human skin equivalent model. The epidermis formed by microcarrier-expanded keratinocytes in this model exhibited morphology similar to native skin. Significantly, the microcarrier technique successfully eliminates the need for a feeder cell layer and hence facilitates development of an improved culture system.
Publisher: IOP Publishing
Date: 14-11-2017
Abstract: This study investigates the use of allyl-functionalized poly(glycidol)s (P(AGE-co-G)) as a cytocompatible cross-linker for thiol-functionalized hyaluronic acid (HA-SH) and the optimization of this hybrid hydrogel as bioink for 3D bioprinting. The chemical cross-linking of gels with 10 wt.% overall polymer concentration was achieved by a UV-induced radical thiol-ene coupling between the thiol and allyl groups. The addition of unmodified high molecular weight HA (1.36 MDa) enabled the rheology to be tuned for extrusion-based bioprinting. The incorporation of additional HA resulted in hydrogels with a lower Young's modulus and a higher swelling ratio, especially in the first 24 h, but a comparable equilibrium swelling for all gels after 24 h. Embedding of human and equine mesenchymal stem cells (MSCs) in the gels and subsequent in vitro culture showed promising chondrogenic differentiation after 21 d for cells from both origins. Moreover, cells could be printed with these gels, and embedded hMSCs showed good cell survival for at least 21 d in culture. To achieve mechanically stable and robust constructs for the envisioned application in articular cartilage, the formulations were adjusted for double printing with thermoplastic poly(ε-caprolactone) (PCL).
Publisher: European Cells and Materials
Date: 21-06-2018
DOI: 10.22203/ECM.V035A23
Publisher: Wiley
Date: 12-01-2023
Abstract: Sacrificial printing allows introduction of architectural cues within engineered tissue constructs. This strategy adopts the use of a 3D‐printed sacrificial ink that is embedded within a bulk hydrogel which is subsequently dissolved to leave open‐channels. However, current conventional sacrificial inks do not recapitulate the dynamic nature of tissue development, such as the temporal presentation of architectural cues matching cellular requirements during different stages of maturation. To address this limitation, a new class of sacrificial inks is developed that exhibits tailorable and programmable delayed dissolution profiles (1–17 days), by exploiting the unique ability of the ruthenium complex and sodium persulfate initiating system to crosslink native tyrosine groups present in non‐chemically modified gelatin. These novel sacrificial inks are also shown to be compatible with a range of biofabrication technologies, including extrusion‐based printing, digital‐light processing, and volumetric bioprinting. Further embedding these sacrificial templates within cell‐laden bulk hydrogels displays precise control over the spatial and temporal introduction of architectural features into cell‐laden hydrogel constructs. This approach demonstrates the unique capacity of delaying dissolution of sacrificial inks to modulate cell behavior, improving the deposition of mineralized matrix and capillary‐like network formation in osteogenic and vasculogenic culture, respectively.
Publisher: Hindawi Limited
Date: 08-11-2012
DOI: 10.1002/TERM.1638
Abstract: Cartilage defects heal imperfectly and osteoarthritic changes develop frequently as a result. Although the existence of specific behaviours of chondrocytes derived from various depth-related zones in vitro has been known for over 20 years, only a relatively small body of in vitro studies has been performed with zonal chondrocytes and current clinical treatment strategies do not reflect these native depth-dependent (zonal) differences. This is surprising since mimicking the zonal organization of articular cartilage in neo-tissue by the use of zonal chondrocyte subpopulations could enhance the functionality of the graft. Although some research groups including our own have made considerable progress in tailoring culture conditions using specific growth factors and biomechanical loading protocols, we conclude that an optimal regime has not yet been determined. Other unmet challenges include the lack of specific zonal cell sorting protocols and limited amounts of cells harvested per zone. As a result, the engineering of functional tissue has not yet been realized and no long-term in vivo studies using zonal chondrocytes have been described. This paper critically reviews the research performed to date and outlines our view of the potential future significance of zonal chondrocyte populations in regenerative approaches for the treatment of cartilage defects. Secondly, we briefly discuss the capabilities of additive manufacturing technologies that can not only create patient-specific grafts directly from medical imaging data sets but could also more accurately reproduce the complex 3D zonal extracellular matrix architecture using techniques such as hydrogel-based cell printing.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.JOCA.2012.06.005
Abstract: Articular cartilage defects are common after joint injuries. When left untreated, the biomechanical protective function of cartilage is gradually lost, making the joint more susceptible to further damage, causing progressive loss of joint function and eventually osteoarthritis (OA). In the process of translating promising tissue-engineering cartilage repair approaches from bench to bedside, pre-clinical animal models including mice, rabbits, goats, and horses, are widely used. The equine species is becoming an increasingly popular model for the in vivo evaluation of regenerative orthopaedic approaches. As there is also an increasing body of evidence suggesting that successful lasting tissue reconstruction requires an implant that mimics natural tissue organization, it is imperative that depth-dependent characteristics of equine osteochondral tissue are known, to assess to what extent they resemble those in humans. Therefore, osteochondral cores (4-8 mm) were obtained from the medial and lateral femoral condyles of equine and human donors. Cores were processed for histology and for biochemical quantification of DNA, glycosaminoglycan (GAG) and collagen content. Equine and human osteochondral tissues possess similar geometrical (thickness) and organizational (GAG, collagen and DNA distribution with depth) features. These comparable trends further underscore the validity of the equine model for the evaluation of regenerative approaches for articular cartilage.
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: 04-2018
DOI: 10.1016/J.TIBTECH.2017.10.015
Abstract: Biofabrication holds the potential to generate constructs that more closely recapitulate the complexity and heterogeneity of tissues and organs than do currently available regenerative medicine therapies. Such constructs can be applied for tissue regeneration or as in vitro 3D models. Biofabrication is maturing and growing, and scientists with different backgrounds are joining this field, underscoring the need for unity regarding the use of terminology. We therefore believe that there is a compelling need to clarify the relationship between the different concepts, technologies, and descriptions of biofabrication that are often used interchangeably or inconsistently in the current literature. Our objective is to provide a guide to the terminology for different technologies in the field which may serve as a reference for the biofabrication community.
Publisher: IOP Publishing
Date: 08-01-2016
DOI: 10.1088/1758-5090/8/1/013001
Abstract: Biofabrication is an evolving research field that has recently received significant attention. In particular, the adoption of Biofabrication concepts within the field of Tissue Engineering and Regenerative Medicine has grown tremendously, and has been accompanied by a growing inconsistency in terminology. This article aims at clarifying the position of Biofabrication as a research field with a special focus on its relation to and application for Tissue Engineering and Regenerative Medicine. Within this context, we propose a refined working definition of Biofabrication, including Bioprinting and Bioassembly as complementary strategies within Biofabrication.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Oxford University Press (OUP)
Date: 07-12-2007
DOI: 10.1111/J.1365-2133.2007.08362.X
Abstract: Chronic venous leg ulcers are a significant cause of pain, immobility and decreased quality of life for patients with these wounds. In view of this, research efforts are focused on multiple factors in the wound environment to obtain information regarding the healing of ulcers. Chronic wound fluid (CWF), containing a complex mixture of proteins, is an important modulator of the wound environment, and therefore we hypothesized that these proteins may be indicators of the status of wounds and their potential to heal or otherwise. To explore this we developed and validated a proteomic approach to analyse CWF. In this study, pooled CWF was depleted of high abundant proteins using immunoaffinity chromatography. The flow-through and bound fractions were collected, concentrated, desalted and analysed using a range of techniques. Each fraction was further separated using two-dimensional (2D) gel electrophoresis and 2D liquid chromatography and analysed using mass spectrometry (MS). Western blot analysis against three high abundant proteins confirmed the selective removal of these proteins from CWF. Critically, one-dimensional and 2D gel electrophoresis indicated that subsequent removal of these proteins enhanced the ability to detect proteins in low abundance in CWF. Further, MS demonstrated that depletion of these abundant proteins increased the detection of other proteins in these s les. Results obtained indicate that this approach significantly improves separation of proteins present in low concentrations in CWF. This will facilitate the identification of biomarkers in s les collected from patients with ulcers and lead to improved patient therapies and wound care approaches.
Publisher: Cambridge University Press (CUP)
Date: 22-11-2018
DOI: 10.1017/S0956792518000657
Abstract: Tissue engineering aims to grow artificial tissues in vitro to replace those in the body that have been damaged through age, trauma or disease. A recent approach to engineer artificial cartilage involves seeding cells within a scaffold consisting of an interconnected 3D-printed lattice of polymer fibres combined with a cast or printed hydrogel, and subjecting the construct (cell-seeded scaffold) to an applied load in a bioreactor. A key question is to understand how the applied load is distributed throughout the construct. To address this, we employ homogenisation theory to derive equations governing the effective macroscale material properties of a periodic, elastic–poroelastic composite. We treat the fibres as a linear elastic material and the hydrogel as a poroelastic material, and exploit the disparate length scales (small inter-fibre spacing compared with construct dimensions) to derive macroscale equations governing the response of the composite to an applied load. This homogenised description reflects the orthotropic nature of the composite. To validate the model, solutions from finite element simulations of the macroscale, homogenised equations are compared to experimental data describing the unconfined compression of the fibre-reinforced hydrogels. The model is used to derive the bulk mechanical properties of a cylindrical construct of the composite material for a range of fibre spacings and to determine the local mechanical environment experienced by cells embedded within the construct.
Publisher: IOP Publishing
Date: 30-06-2023
Abstract: To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is to investigate the potential of combining extrusion-based bioprinting (EBB) and melt electrowriting for the fabrication of a myocardial construct with a precisely patterned pre-vascular pathway. Gelatin methacryloyl (GelMA) was investigated as a base hydrogel for the respective myocardial and vascular bioinks with collagen, Matrigel and fibrinogen as interpenetrating polymers to support myocardial functionality. Subsequently, extrusion-based printability and viability were investigated to determine the optimal processing parameters for printing into melt electrowritten meshes. Finally, an anatomically inspired vascular pathway was implemented in a dual EBB set-up into melt electrowritten meshes, creating a patterned pre-vascularized myocardial construct. It was determined that a blend of 5% GelMA and 0.8 mg·ml −1 collagen with a low crosslinked density was optimal for myocardial cellular arrangement and alignment within the constructs. For the vascular fraction, the optimized formulation consisted of 5% GelMA, 0.8 mg·ml −1 collagen and 1 mg·ml −1 fibrinogen with a higher crosslinked density, which led to enhanced vascular cell connectivity. Printability assessment confirmed that the optimized bioinks could effectively fill the microfiber mesh while supporting cell viability (∼70%). Finally, the two bioinks were applied using a dual EBB system for the fabrication of a pre-vascular pathway with the shape of a left anterior descending artery within a myocardial construct, whereby the distinct cell populations could be visualized in their respective patterns up to D14. This research investigated the first step towards developing a thick engineered cardiac tissue construct in which a pre-vascularization pathway is fabricated within a myocardial construct.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.JOCA.2010.10.005
Abstract: Equilibrium Partitioning of an Ionic Contrast agent with microcomputed tomography (EPIC-μCT) is a non-invasive technique to quantify and visualize the three-dimensional distribution of glycosaminoglycans (GAGs) in fresh cartilage tissue. However, it is unclear whether this technique is applicable to already fixed tissues. Therefore, this study aimed at investigating whether formalin fixation of bovine cartilage affects X-ray attenuation, and thus the interpretation of EPIC-μCT data. Osteochondral s les (n=24) were incubated with ioxaglate, an ionic contrast agent, for 22h prior to μCT scanning. The s les were scanned in both formalin-fixed and fresh conditions. GAG content was measured using a biochemical assay and normalized to wet weight, dry weight, and water content to determine potential reasons for differences in X-ray attenuation. The expected zonal distribution of contrast agent/GAGs was observed for both fixed and fresh cartilage specimens. However, despite no significant differences in GAG concentrations or physical properties between fixed and fresh s les, the average attenuation levels of formalin-fixed cartilage were 14.3% lower than in fresh s les. EPIC-μCT is useful for three-dimensional visualization of GAGs in formalin-fixed cartilage. However, a significant reduction in X-ray attenuation for fixed (compared to fresh) cartilage must be taken into account and adjusted for accordingly when quantifying GAG concentrations using EPIC-μCT.
Publisher: Wiley
Date: 26-04-2019
Abstract: In this study, the cyto-compatibility and cellular functionality of cell-laden gelatin-methacryloyl (Gel-MA) hydrogels fabricated using a set of photo-initiators which absorb in 400-450 nm of the visible light range are investigated. Gel-MA hydrogels cross-linked using ruthenium (Ru) and sodium persulfate (SPS), are characterized to have comparable physico-mechanical properties as Gel-MA gels photo-polymerized using more conventionally adopted photo-initiators, such as 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959) and lithium phenyl(2,4,6-trimethylbenzoyl) phosphinate (LAP). It is demonstrated that the Ru/SPS system has a less adverse effect on the viability and metabolic activity of human articular chondrocytes encapsulated in Gel-MA hydrogels for up to 35 days. Furthermore, cell-laden constructs cross-linked using the Ru/SPS system have significantly higher glycosaminoglycan content and re-differentiation capacity as compared to cells encapsulated using I2959 and LAP. Moreover, the Ru/SPS system offers significantly greater light penetration depth as compared to the I2959 system, allowing thick (10 mm) Gel-MA hydrogels to be fabricated with homogenous cross-linking density throughout the construct. These results demonstrate the considerable advantages of the Ru/SPS system over traditional UV polymerizing systems in terms of clinical relevance and practicability for applications such as cell encapsulation, biofabrication, and in situ cross-linking of injectable hydrogels.
Publisher: Wiley
Date: 23-04-2020
Publisher: Springer Science and Business Media LLC
Date: 28-04-2015
DOI: 10.1038/NCOMMS7933
Abstract: Despite intensive research, hydrogels currently available for tissue repair in the musculoskeletal system are unable to meet the mechanical, as well as the biological, requirements for successful outcomes. Here we reinforce soft hydrogels with highly organized, high-porosity microfibre networks that are 3D-printed with a technique termed as melt electrospinning writing. We show that the stiffness of the gel/scaffold composites increases synergistically (up to 54-fold), compared with hydrogels or microfibre scaffolds alone. Modelling affirms that reinforcement with defined microscale structures is applicable to numerous hydrogels. The stiffness and elasticity of the composites approach that of articular cartilage tissue. Human chondrocytes embedded in the composites are viable, retain their round morphology and are responsive to an in vitro physiological loading regime in terms of gene expression and matrix production. The current approach of reinforcing hydrogels with 3D-printed microfibres offers a fundament for producing tissue constructs with biological and mechanical compatibility.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.EXER.2009.06.005
Abstract: Insulin-like growth factor binding proteins (IGFBPs) are prime regulators of IGF-action in numerous cell types including the retinal pigment epithelium (RPE). The RPE performs several functions essential for vision, including growth factor secretion and waste removal via a phagocytic process mediated in part by vitronectin (Vn). In the course of studying the effects of IGFBPs on IGF-mediated VEGF secretion and Vn-mediated phagocytosis in the RPE cell line ARPE-19, we have discovered that these cells avidly ingest synthetic microspheres (2.0 mum diameter) coated with IGFBPs. Given the novelty of this finding and the established role for endocytosis in mediating IGFBP actions in other cell types, we have explored the potential role of candidate cell surface receptors. Moreover, we have examined the role of key IGFBP structural motifs, by comparing responses to three members of the IGFBP family (IGFBP-3, IGFBP-4 and IGFBP-5) which display overlapping variations in primary structure and glycosylation status. Coating of microspheres (FluoSpheres((R)), sulfate modified polystyrene filled with a fluorophore) was conducted at 37 degrees C for 1 h using 20 microg/mL of test protein, followed by extensive washing. Binding of proteins was confirmed using a microBCA assay. The negative control consisted of microspheres treated with 0.1% bovine serum albumin (BSA), and all test s les were post-treated with BSA in an effort to coat any remaining free protein binding sites, which might otherwise encourage non-specific interactions with the cell surface. Serum-starved cultures of ARPE-19 cells were incubated with microspheres for 24 h, using a ratio of approximately 100 microspheres per cell. Uptake of microspheres was quantified using a fluorometer and was confirmed visually by confocal fluorescence microscopy. The ARPE-19 cells displayed little affinity for BSA-treated microspheres, but avidly ingested large quantities of those pre-treated with Vn (ANOVA p < 0.001). Strong responses were also observed towards recombinant formulations of non-glycosylated IGFBP-3, glycosylated IGFBP-3 and glycosylated IGFBP-5 (all p < 0.001), while glycosylated IGFBP-4 induced a relatively minor response (p < 0.05). The response to IGFBP-3 was unaffected in the presence of excess soluble IGFBP-3, IGF-I or Vn. Likewise, soluble IGFBP-3 did not induce uptake of BSA-treated microspheres. Antibodies to either the transferrin receptor or type 1 IGF-receptor displayed slight inhibitory effects on responses to IGFBPs and Vn. Heparin abolished responses to Vn, IGFBP-5 and non-glycosylated IGFBP-3, but only partially inhibited the response to glycosylated IGFBP-3. Our results demonstrate for the first time IGFBP-mediated endocytosis in ARPE-19 cells and suggest roles for the IGFBP-heparin-binding domain and glycosylation status. These findings have important implications for understanding the mechanisms of IGFBP actions on the RPE, and in particular suggest a role for IGFBP-endocytosis.
Publisher: Wiley
Date: 24-06-2020
DOI: 10.1002/JOR.24780
Abstract: Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post‐traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 s les). Three age‐matched nonoperated ponies served as controls (six s les). The s les were imaged at 9.4 T. The measured qMRI parameters included T 1 , T 2 , continuous‐wave T 1ρ (CWT 1ρ ), adiabatic T 1ρ (AdT 1ρ ), and T 2ρ (AdT 2ρ ) and relaxation along a fictitious field (T RAFF ). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full‐thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T 1 , CWT 1ρ , and AdT 1ρ in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT 1ρ was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin‐locking litudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters ( ρ = −0.531 to −0.757). T 1 , low spin‐lock litude CWT 1ρ , and AdT 1ρ were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T 1 , CWT 1ρ , and AdT 1ρ in evaluation of compositional and structural changes in cartilage.
Publisher: Elsevier BV
Date: 06-2008
Abstract: Topical administration of growth factors has displayed some potential in wound healing, but variable efficacy, high doses, and costs have h ered their implementation. Moreover, this approach ignores the fact that wound repair is driven by interactions between multiple growth factors and extracellular matrix (ECM) proteins. We report herein that complexes comprising IGF and IGF-binding proteins bound to the ECM protein vitronectin (VN) significantly enhance cellular functions relevant to wound repair in human skin keratinocytes in two- and three-dimensional in vitro cell models and are active, even in the presence of wound fluid. Moreover, these responses require activation of both the IGF receptor and the VN-binding alpha(v) integrins. Further, we assessed the complexes as a topical agent in the treatment of deep dermal partial thickness burns in a porcine model. This pilot study revealed that the complexes may hold promise as a wound healing therapy. Critically, the significant responses observed in vitro and the encouraging preliminary data in vivo were obtained with nanogram doses of growth factors. This suggests that coupling delivery of growth factors to ECM proteins such as VN may ultimately prove to be a more effective strategy for developing a wound healing therapy.
Publisher: IOP Publishing
Date: 02-07-2013
DOI: 10.1088/1758-5082/5/3/035007
Abstract: Additive manufacturing in the field of regenerative medicine aims to fabricate organized tissue-equivalents. However, the control over shape and composition of biofabricated constructs is still a challenge and needs to be improved. The current research aims to improve shape, by converging a number of biocompatible, quality construction materials into a single three-dimensional fiber deposition process. To demonstrate this, several models of complex anatomically shaped constructs were fabricated by combined deposition of poly(vinyl alcohol), poly(ε-caprolactone), gelatin methacrylamide/gellan gum and alginate hydrogel. Sacrificial components were co-deposited as temporary support for overhang geometries and were removed after fabrication by immersion in aqueous solutions. Embedding of chondrocytes in the gelatin methacrylamide/gellan component demonstrated that the fabrication and the sacrificing procedure did not affect cell viability. Further, it was shown that anatomically shaped constructs can be successfully fabricated, yielding advanced porous thermoplastic polymer scaffolds, layered porous hydrogel constructs, as well as reinforced cell-laden hydrogel structures. In conclusion, anatomically shaped tissue constructs of clinically relevant sizes can be generated when employing multiple building and sacrificial materials in a single biofabrication session. The current techniques offer improved control over both internal and external construct architecture underscoring its potential to generate customized implants for human tissue regeneration.
Publisher: Springer Science and Business Media LLC
Date: 06-05-2019
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: Wiley
Date: 23-08-2013
Abstract: With advances in tissue engineering, the possibility of regenerating injured tissue or failing organs has become a realistic prospect for the first time in medical history. Tissue engineering - the combination of bioactive materials with cells to generate engineered constructs that functionally replace lost and/or damaged tissue - is a major strategy to achieve this goal. One facet of tissue engineering is biofabrication, where three-dimensional tissue-like structures composed of biomaterials and cells in a single manufacturing procedure are generated. Cell-laden hydrogels are commonly used in biofabrication and are termed "bioinks". Hydrogels are particularly attractive for biofabrication as they recapitulate several features of the natural extracellular matrix and allow cell encapsulation in a highly hydrated mechanically supportive three-dimensional environment. Additionally, they allow for efficient and homogeneous cell seeding, can provide biologically-relevant chemical and physical signals, and can be formed in various shapes and biomechanical characteristics. However, despite the progress made in modifying hydrogels for enhanced bioactivation, cell survival and tissue formation, little attention has so far been paid to optimize hydrogels for the physico-chemical demands of the biofabrication process. The resulting lack of hydrogel bioinks have been identified as one major hurdle for a more rapid progress of the field. In this review we summarize and focus on the deposition process, the parameters and demands of hydrogels in biofabrication, with special attention to robotic dispensing as an approach that generates constructs of clinically relevant dimensions. We aim to highlight this current lack of effectual hydrogels within biofabrication and initiate new ideas and developments in the design and tailoring of hydrogels. The successful development of a "printable" hydrogel that supports cell adhesion, migration, and differentiation will significantly advance this exciting and promising approach for tissue engineering.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6LC01566B
Abstract: The use of 3D-printing in bovine oviduct epithelial cell cultures allows better bio-mimicking of embryo production than classical in vitro fertilization.
Publisher: Wiley
Date: 15-01-2020
Abstract: Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (<1 min), allowing encapsulation of cells at significantly higher cell densities (15 million cells mL
Publisher: Wiley
Date: 11-10-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
DOI: 10.1097/GOX.0000000000001146
Abstract: The limited cranial skin covering auricular implants is an important yet underrated factor in auricular reconstruction for both reconstruction surgery and tissue engineering strategies. We report exact measurements on skin deficiency in microtia patients and propose an accessible preoperative method for these measurements. Plaster ear models (n = 11 male:female = 2:1) of lobular-type microtia patients admitted to the University Medical Center Utrecht in The Netherlands were scanned using a micro-computed tomographic scanner or a cone-beam computed tomographic scanner. The resulting images were converted into mesh models from which the surface area could be calculated. The mean total skin area of an adult-size healthy ear was 47.3 cm 2 , with 49.0 cm 2 in men and 44.3 cm 2 in women. Microtia ears averaged 14.5 cm 2 , with 15.6 cm 2 in men and 12.6 cm 2 in women. The amount of skin deficiency was 25.4 cm 2 , with 26.7 cm 2 in men and 23.1 cm 2 in women. This study proposes a novel method to provide quantitative data on the skin surface area of the healthy adult auricle and the amount of skin deficiency in microtia patients. We demonstrate that the microtia ear has less than 50% of skin available compared with healthy ears. Limited skin availability in microtia patients can lead to healing problems after auricular reconstruction and poses a significant challenge in the development of tissue-engineered cartilage implants. The results of this study could be used to evaluate outcomes and investigate new techniques with regard to tissue-engineered auricular constructs.
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.JBIOMECH.2018.06.012
Abstract: As articular cartilage is an avascular tissue, the transport of nutrients and cytokines through the tissue is essential for the health of cells, i.e. chondrocytes. Transport of specific contrast agents through cartilage has been investigated to elucidate cartilage quality. In laboratory, pre-clinical and clinical studies, imaging techniques such as magnetic imaging resonance (MRI), computed tomography (CT) and fluorescent microscopy have been widely employed to visualize and quantify solute transport in cartilage. Many parameters related to the physico-chemical properties of the solute, such as molecular weight, net charge and chemical structure, have a profound effect on the transport characteristics. Information on the interplay of the solute parameters with the imaging-dependent parameters (e.g. resolution, scan and acquisition time) could assist in selecting the most optimal imaging systems and data analysis tools in a specific experimental set up. Here, we provide a comprehensive review of various imaging systems to investigate solute transport properties in articular cartilage, by discussing their potentials and limitations. The presented information can serve as a guideline for applications in cartilage imaging and therapeutics delivery and to improve understanding of the set-up of solute transport experiments in articular cartilage.
Publisher: OSA
Date: 2018
Publisher: Wiley
Date: 12-08-2019
Publisher: Mary Ann Liebert Inc
Date: 09-2007
Abstract: Oxygen is a potent modulator of cell function and wound repair in vivo. The lack of oxygen (hypoxia) can create a potentially lethal environment and limit cellular respiration and growth or, alternatively, enhance the production of the specific extracellular matrix components and increase angiogenesis through the hypoxia-inducible factor-1 pathway. For the in vitro generation of clinically relevant tissue-engineered grafts, these ergent actions of hypoxia should be addressed. Diffusion through culture medium and tissue typically limits oxygen transport in vitro, leading to hypoxic regions and limiting the viable tissue thickness. Approaches to overcoming the transport limitations include culture with bioreactors, scaffolds with artificial microvasculature, oxygen carriers, and hyperbaric oxygen chambers. As an alternate approach, angiogenesis after implantation may be enhanced by incorporating endothelial cells, genetically modified cells, or specific factors (including vascular endothelial growth factor) into the scaffold or exposing the graft to a hypoxic environment just before implantation. Better understanding of the roles of hypoxia will help prevent common problems and exploit potential benefits of hypoxia in engineered tissues.
Publisher: IOP Publishing
Date: 11-05-2018
Abstract: Lithography-based three-dimensional (3D) printing technologies allow high spatial resolution that exceeds that of typical extrusion-based bioprinting approaches, allowing to better mimic the complex architecture of biological tissues. Additionally, lithographic printing via digital light processing (DLP) enables fabrication of free-form lattice and patterned structures which cannot be easily produced with other 3D printing approaches. While significant progress has been dedicated to the development of cell-laden bioinks for extrusion-based bioprinting, less attention has been directed towards the development of cyto-compatible bio-resins and their application in lithography-based biofabrication, limiting the advancement of this promising technology. In this study, we developed a new bio-resin based on methacrylated poly(vinyl alcohol) (PVA-MA), gelatin-methacryloyl (Gel-MA) and a transition metal-based visible light photoinitiator. The utilization of a visible light photo-initiating system displaying high molar absorptivity allowed the bioprinting of constructs with high resolution features, in the range of 25-50 μm. Biofunctionalization of the resin with 1 wt% Gel-MA allowed long term survival (>90%) of encapsulated cells up to 21 d, and enabled attachment and spreading of endothelial cells seeded on the printed hydrogels. Cell-laden hydrogel constructs of high resolution with complex and ordered architecture were successfully bioprinted, where the encapsulated cells remained viable, homogenously distributed and functional. Bone and cartilage tissue synthesis was confirmed by encapsulated stem cells, underlining the potential of these DLP-bioprinted hydrogels for tissue engineering and biofabrication. Overall, the PVA-MA/Gel-MA bio-resin is a promising material for biofabrication and provides important cues for the further development of lithography-based bioprinting of complex, free-form living tissue analogues.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2018
DOI: 10.1038/S41598-018-31670-5
Abstract: Arthroscopic assessment of articular tissues is highly subjective and poorly reproducible. To ensure optimal patient care, quantitative techniques ( e.g ., near infrared spectroscopy (NIRS)) could substantially enhance arthroscopic diagnosis of initial signs of post-traumatic osteoarthritis (PTOA). Here, we demonstrate, for the first time, the potential of arthroscopic NIRS to simultaneously monitor progressive degeneration of cartilage and subchondral bone in vivo in Shetland ponies undergoing different experimental cartilage repair procedures. Osteochondral tissues adjacent to the repair sites were evaluated using an arthroscopic NIRS probe and significant ( p 0.05) degenerative changes were observed in the tissue properties when compared with tissues from healthy joints. Artificial neural networks (ANN) enabled reliable ( ρ = 0.63–0.87, NMRSE = 8.5–17.2%, RPIQ = 1.93–3.03) estimation of articular cartilage biomechanical properties, subchondral bone plate thickness and bone mineral density (BMD), and subchondral trabecular bone thickness, bone volume fraction (BV), BMD, and structure model index (SMI) from in vitro spectral data. The trained ANNs also reliably predicted the properties of an independent in vitro test group ( ρ = 0.54–0.91, NMRSE = 5.9–17.6%, RPIQ = 1.68 – 3.36). However, predictions based on arthroscopic NIR spectra were less reliable ( ρ = 0.27–0.74, NMRSE = 14.5–24.0%, RPIQ = 1.35 – 1.70), possibly due to errors introduced during arthroscopic spectral acquisition. Adaptation of NIRS could address the limitations of conventional arthroscopy through quantitative assessment of lesion severity and extent, thereby enhancing detection of initial signs of PTOA. This would be of high clinical significance, for ex le, when conducting orthopaedic repair surgeries.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-06-2006
Publisher: Wiley
Date: 12-05-2021
DOI: 10.1002/JOR.25066
Abstract: To prevent the progression of posttraumatic osteoarthritis, assessment of cartilage composition is critical for effective treatment planning. Posttraumatic changes include proteoglycan (PG) loss and elevated water content. Quantitative dual‐energy computed tomography (QDECT) provides a means to diagnose these changes. Here, we determine the potential of QDECT to evaluate tissue quality surrounding cartilage lesions in an equine model, hypothesizing that QDECT allows detection of posttraumatic degeneration by providing quantitative information on PG and water contents based on the partitions of cationic and nonionic agents in a contrast mixture. Posttraumatic osteoarthritic s les were obtained from a cartilage repair study in which full‐thickness chondral defects were created surgically in both stifles of seven Shetland ponies. Control s les were collected from three nonoperated ponies. The experimental ( n = 14) and control s les ( n = 6) were immersed in the contrast agent mixture and the distributions of the agents were determined at various diffusion time points. As a reference, equilibrium moduli, dynamic moduli, and PG content were measured. Significant differences ( p 0.05) in partitions between the experimental and control s les were demonstrated with cationic contrast agent at 30 min, 60 min, and 20 h, and with non‐ionic agent at 60 and 120 min. Significant Spearman's rank correlations were obtained at 20 and 24 h ( ρ = 0.482–0.693) between the partition of cationic contrast agent, cartilage biomechanical properties, and PG content. QDECT enables evaluation of posttraumatic changes surrounding a lesion and quantification of PG content, thus advancing the diagnostics of the extent and severity of cartilage injuries.
Publisher: Mary Ann Liebert Inc
Date: 06-2009
Publisher: Public Library of Science (PLoS)
Date: 12-2014
Publisher: Wiley
Date: 03-2007
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.BONE.2019.07.001
Abstract: Since Galileo's days the effect of size on the anatomical characteristics of the structural elements of the body has been a subject of interest. However, the effects of scaling at tissue level have received little interest and virtually no data exist on the subject with respect to the osteochondral unit in the joint, despite this being one of the most lesion-prone and clinically relevant parts of the musculoskeletal system. Imaging techniques, including Fourier transform infrared imaging, polarized light microscopy and micro computed tomography, were combined to study the response to increasing body mass of the osteochondral unit. We analyzed the effect of scaling on structural characteristics of articular cartilage, subchondral plate and the supporting trabecular bone, across a wide range of mammals at microscopic level. We demonstrated that, while total cartilage thickness scales to body mass in a negative allometric fashion, thickness of different cartilage layers did not. Cartilage tissue layers were found to adapt to increasing loads principally in the deep zone with the superficial layers becoming relatively thinner. Subchondral plate thickness was found to have no correlation to body mass, nor did bone volume fraction. The underlying trabecular bone was found to have thicker trabeculae (r=0.75, p<0.001), as expected since this structure carries most loads and plays a role in force mitigation. The results of this study suggest that the osteochondral tissue structure has remained remarkably preserved across mammalian species during evolution, and that in particular, the trabecular bone carries the adaptation to the increasing body mass.
Publisher: Elsevier
Date: 2017
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C3TB21280G
Start Date: 10-2005
End Date: 10-2008
Amount: $590,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2007
End Date: 12-2011
Amount: $231,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2008
End Date: 12-2010
Amount: $563,933.00
Funder: Australian Research Council
View Funded Activity