ORCID Profile
0000-0002-6669-7766
Current Organisations
Western Sydney University
,
Queensland University of Technology
,
University of the Sunshine Coast
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Research Topics
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.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biomaterials | Biomedical Engineering | Biomechanical Engineering | Medical Devices | Macromolecular and Materials Chemistry | Synthesis of Materials | Biomaterials | Nanochemistry and Supramolecular Chemistry | Orthopaedics | Medical Biotechnology | Logistics and Supply Chain Management | Orthopaedics | Human Movement and Sports Science | Vertebrate Biology | Cellular Interactions (Incl. Adhesion, Matrix, Cell Wall) | Mechanical Engineering | Numerical Modelling and Mechanical Characterisation | Biomechanics | Biomedical Engineering not elsewhere classified | Composite and Hybrid Materials | Regenerative Medicine (incl. Stem Cells and Tissue Engineering)
ANZSRC Socio-Economic Objective (SEO)
Skeletal System and Disorders (incl. Arthritis) | Expanding Knowledge in the Medical and Health Sciences | Expanding Knowledge in Engineering | Manufacturing not elsewhere classified | Expanding Knowledge in the Biological Sciences | Polymeric Materials (e.g. Paints) | Technological and Organisational Innovation | Surgical methods and procedures | Expanding Knowledge in the Chemical Sciences | Human Pharmaceutical Products not elsewhere classified | Skeletal system and disorders (incl. arthritis) |
Related Links
Publications
Structural analysis of photocrosslinkable methacryloyl-modified protein derivatives
Publisher: Elsevier BV
Date: 09-2017
The Mechanisms of Human Renal Epithelial Cell Modulation of Autologous Dendritic Cell Phenotype and Function
Publisher: Public Library of Science (PLoS)
Date: 31-07-2015
Non-invasive identification of proteoglycans and chondrocyte differentiation state by Raman microspectroscopy
Publisher: Wiley
Date: 08-06-2012
Abstract: Proteoglycans (PGs) are crucial extracellular matrix (ECM) components that are present in all tissues and organs. Pathological remodeling of these macromolecules can lead to severe diseases such as osteoarthritis or rheumatoid arthritis. To date, PG-associated ECM alterations are routinely diagnosed by invasive analytical methods. Here, we employed Raman microspectroscopy, a laser-based, marker-free and non-destructive technique that allows the generation of spectra with peaks originating from molecular vibrations within a s le, to identify specific Raman bands that can be assigned to PGs within human and porcine cartilage s les and chondrocytes. Based on the non-invasively acquired Raman spectra, we further revealed that a prolonged in vitro culture leads to phenotypic alterations of chondrocytes, resulting in a decreased PG synthesis rate and loss of lipid contents. Our results are the first to demonstrate the applicability of Raman microspectroscopy as an analytical and potential diagnostic tool for non-invasive cell and tissue state monitoring of cartilage in biomedical research.
Biofabricated soft network composites for cartilage tissue engineering
Publisher: IOP Publishing
Date: 12-05-2017
Abstract: Articular cartilage from a material science point of view is a soft network composite that plays a critical role in load-bearing joints during dynamic loading. Its composite structure, consisting of a collagen fiber network and a hydrated proteoglycan matrix, gives rise to the complex mechanical properties of the tissue including viscoelasticity and stress relaxation. Melt electrospinning writing allows the design and fabrication of medical grade polycaprolactone (mPCL) fibrous networks for the reinforcement of soft hydrogel matrices for cartilage tissue engineering. However, these fiber-reinforced constructs underperformed under dynamic and prolonged loading conditions, suggesting that more targeted design approaches and material selection are required to fully exploit the potential of fibers as reinforcing agents for cartilage tissue engineering. In the present study, we emulated the proteoglycan matrix of articular cartilage by using highly negatively charged star-shaped poly(ethylene glycol)/heparin hydrogel (sPEG/Hep) as the soft matrix. These soft hydrogels combined with mPCL melt electrospun fibrous networks exhibited mechanical anisotropy, nonlinearity, viscoelasticity and morphology analogous to those of their native counterpart, and provided a suitable microenvironment for in vitro human chondrocyte culture and neocartilage formation. In addition, a numerical model using the p-version of the finite element method (p-FEM) was developed in order to gain further insights into the deformation mechanisms of the constructs in silico, as well as to predict compressive moduli. To our knowledge, this is the first study presenting cartilage tissue-engineered constructs that capture the overall transient, equilibrium and dynamic biomechanical properties of human articular cartilage.
A single day of TGF-β1 exposure activates chondrogenic and hypertrophic differentiation pathways in bone marrow-derived stromal cells
Publisher: Springer Science and Business Media LLC
Date: 04-01-2021
DOI: 10.1038/S42003-020-01520-0
Abstract: Virtually all bone marrow-derived stromal cell (BMSC) chondrogenic induction cultures include greater than 2 weeks exposure to transforming growth factor-β (TGF-β), but fail to generate cartilage-like tissue suitable for joint repair. Herein we used a micro -pellet model (5 × 10 3 BMSC each) to determine the duration of TGF-β1 exposure required to initiate differentiation machinery, and to characterize the role of intrinsic programming. We found that a single day of TGF-β1 exposure was sufficient to trigger BMSC chondrogenic differentiation and tissue formation, similar to 21 days of TGF-β1 exposure. Despite cessation of TGF-β1 exposure following 24 hours, intrinsic programming mediated further chondrogenic and hypertrophic BMSC differentiation. These important behaviors are obfuscated by diffusion gradients and heterogeneity in commonly used macro -pellet models (2 × 10 5 BMSC each). Use of more homogenous micro -pellet models will enable identification of the critical differentiation cues required, likely in the first 24-hours, to generate high quality cartilage-like tissue from BMSC.
Osteoimmunomodulatory Nanoparticles for Bone Regeneration
Publisher: MDPI AG
Date: 10-02-2023
DOI: 10.3390/NANO13040692
Abstract: Treatment of large bone fractures remains a challenge for orthopedists. Bone regeneration is a complex process that includes skeletal cells such as osteoblasts, osteoclasts, and immune cells to regulate bone formation and resorption. Osteoimmunology, studying this complicated process, has recently been used to develop biomaterials for advanced bone regeneration. Ideally, a biomaterial shall enable a timely switch from early stage inflammatory (to recruit osteogenic progenitor cells) to later-stage anti-inflammatory (to promote differentiation and terminal osteogenic mineralization and model the microstructure of bone tissue) in immune cells, especially the M1-to-M2 phenotype switch in macrophage populations, for bone regeneration. Nanoparticle (NP)-based advanced drug delivery systems can enable the controlled release of therapeutic reagents and the delivery of therapeutics into specific cell types, thereby benefiting bone regeneration through osteoimmunomodulation. In this review, we briefly describe the significance of osteoimmunology in bone regeneration, the advancement of NP-based approaches for bone regeneration, and the application of NPs in macrophage-targeting drug delivery for advanced osteoimmunomodulation.
Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs
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.
Enhancing structural integrity of hydrogels by using highly organised melt electrospun fibre constructs
Publisher: Elsevier BV
Date: 11-2015
A tumour-spheroid manufacturing and cryopreservation process that yields a highly reproducible product ready for direct use in drug screening assays
Publisher: The Royal Society
Date: 10-2023
Collagenase treatment appears to improve cartilage tissue integration but damage to collagen networks is likely permanent
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/20417314221074207
Abstract: When repairing cartilage defects a major challenge is achieving high-quality integration between the repair tissue and adjacent native cartilage. Matrix-rich cartilage is not easily remodeled, motivating several studies to trial enzyme treatment of the tissue interface to facilitate remodeling and integration. Studying and optimizing such processes is tedious, as well as potentially expensive, and thus simpler models are needed to evaluate the merits of enzyme treatment on cartilage tissue integration. Herein, we used engineered cartilage microtissues formed from bone marrow-derived stromal cells (BMSC) or expanded articular chondrocytes (ACh) to study the impact of enzyme treatment on cartilage tissue integration and matrix remodeling. A 5-min treatment with collagenase appeared to improve cartilage microtissue integration, while up to 48 h treatment with hyaluronidase did not. Alcian blue and anti-collagen II staining suggested that collagenase treatment did facilitate near seamless integration of cartilage microtissues. Microtissue sections were stained with Picrosirius red and characterized using polarized light microscopy, revealing that in idual microtissues contained a collagen network organized in concentric shells. While collagenase treatment appeared to improve tissue integration, assessment of the collagen fibers with polarized light indicated that enzymatically damaged networks were not remodeled nor restored during subsequent culture. This model and these data paradoxically suggest that collagen network disruption is required to improve cartilage tissue integration, but that the disrupted collagen networks are unlikely to subsequently be restored. Future studies should attempt to limit collagen network disruption to the surface of the cartilage, and we recommend using Picrosirius red staining and polarized light to assess the quality of matrix remodeling and integration.
Photo‐Cross‐Linkable, Injectable, and Highly Adhesive GelMA‐Glycol Chitosan Hydrogels for Cartilage Repair
Publisher: Wiley
Date: 09-09-1970
A novel bioreactor system for biaxial mechanical loading enhances the properties of tissue-engineered human cartilage
Publisher: Springer Science and Business Media LLC
Date: 05-12-2017
DOI: 10.1038/S41598-017-16523-X
Abstract: The ex vivo engineering of autologous cartilage tissues has the potential to revolutionize the clinical management of joint disorders. Yet, high manufacturing costs and variable outcomes associated with tissue-engineered implants are still limiting their application. To improve clinical outcomes and facilitate a wider use of engineered tissues, automated bioreactor systems capable of enhancing and monitoring neotissues are required. Here, we developed an innovative system capable of applying precise uni- or biaxial mechanical stimulation to developing cartilage neotissues in a tightly controlled and automated fashion. The bioreactor allows for simple control over the loading parameters with a user-friendly graphical interface and is equipped with a load cell for monitoring tissue maturation. Applying our bioreactor, we demonstrate that human articular chondrocytes encapsulated in hydrogels composed of gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA) respond to uni- and biaxial mechanical stimulation by upregulation of hyaline cartilage-specific marker genes. We further demonstrate that intermittent biaxial mechanostimulation enhances accumulation of hyaline cartilage-specific extracellular matrix. Our study underlines the stimulatory effects of mechanical loading on the biosynthetic activity of human chondrocytes in engineered constructs and the need for easy-to-use, automated bioreactor systems in cartilage tissue engineering.
Immunogold FIB‐SEM: Combining Volumetric Ultrastructure Visualization with 3D Biomolecular Analysis to Dissect Cell–Environment Interactions
Publisher: Wiley
Date: 13-06-2019
Cartilage regeneration using zonal chondrocyte subpopulations: a promising approach or an overcomplicated strategy?
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.
A Hydrogel Model Incorporating 3D-Plotted Hydroxyapatite for Osteochondral Tissue Engineering
Publisher: MDPI AG
Date: 14-04-2016
DOI: 10.3390/MA9040285
Evaluation of the impact of freezing preparation techniques on the characterisation of alginate hydrogels by cryo-SEM
Publisher: Elsevier BV
Date: 09-2016
Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1186/S13287-020-02045-3
Abstract: Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. The objective of this study was to characterise ovine BMSC (oBMSC) in vitro, and to evaluate the capacity of chondrogenic micro-pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation capacity. oBMSC micro-pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O 2 . The capacity of cartilage micro-pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction ingredient, 3-Isobutyl-1-methylxanthine (IBMX), was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O 2 atmosphere. Micro-pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro-pellets. While oACh micro-pellets formed cartilage-like repair tissue in sheep, oBMSC micro-pellets did not. The sensitivity of oBMSC, compared to human BMSC, to IBMX in standard adipogenic assays highlights species-associated differences. Micro-pellets manufactured from oACh were more effective than micro-pellets manufactured from oBMSC in the repair of osteochondral defects in sheep. While oBMSC can be driven to form cartilage-like tissue in vitro, the effective use of these cells in cartilage repair will depend on the successful mitigation of hypertrophy and tissue integration.
Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles
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.
Engineering Anisotropic Muscle Tissue using Acoustic Cell Patterning
Publisher: Wiley
Date: 12-09-2018
Hydrogel: A Potential Material for Bone Tissue Engineering Repairing the Segmental Mandibular Defect
Publisher: MDPI AG
Date: 05-10-2022
Abstract: Free flap surgery is currently the only successful method used by surgeons to reconstruct critical-sized defects of the jaw, and is commonly used in patients who have had bony lesions excised due to oral cancer, trauma, infection or necrosis. However, donor site morbidity remains a significant flaw of this strategy. Various biomaterials have been under investigation in search of a suitable alternative for segmental mandibular defect reconstruction. Hydrogels are group of biomaterials that have shown their potential in various tissue engineering applications, including bone regeneration, both through in vitro and in vivo pre-clinical animal trials. This review discusses different types of hydrogels, their fabrication techniques, 3D printing, their potential for bone regeneration, outcomes, and the limitations of various hydrogels in preclinical models for bone tissue engineering. This review also proposes a modified technique utilizing the potential of hydrogels combined with scaffolds and cells for efficient reconstruction of mandibular segmental defects.
Intermittent parathyroid hormone (1–34) supplementation of bone marrow stromal cell cultures may inhibit hypertrophy, but at the expense of chondrogenesis
Publisher: Springer Science and Business Media LLC
Date: 29-07-2020
DOI: 10.1186/S13287-020-01820-6
Abstract: Bone marrow stromal cells (BMSC) have promise in cartilage tissue engineering, but for their potential to be fully realised, the propensity to undergo hypertrophy must be mitigated. The literature contains erging reports on the effect of parathyroid hormone (PTH) on BMSC differentiation. Cartilage tissue models can be heterogeneous, confounding efforts to improve media formulations. Herein, we use a novel microwell platform (the Microwell-mesh ) to manufacture hundreds of small-diameter homogeneous micro -pellets and use this high-resolution assay to quantify the influence of constant or intermittent PTH(1–34) medium supplementation on BMSC chondrogenesis and hypertrophy. Micro -pellets were manufactured from 5000 BMSC each and cultured in standard chondrogenic media supplemented with (1) no PTH, (2) intermittent PTH, or (3) constant PTH. Relative to control chondrogenic cultures, BMSC micro -pellets exposed to intermittent PTH had reduced hypertrophic gene expression following 1 week of culture, but this was accompanied by a loss in chondrogenesis by the second week of culture. Constant PTH treatment was detrimental to chondrogenic culture. This study provides further clarity on the role of PTH on chondrogenic differentiation in vitro and suggests that while PTH may mitigate BMSC hypertrophy, it does so at the expense of chondrogenesis.
Human proximal tubule epithelial cells modulate autologous B-cell function
Publisher: Oxford University Press (OUP)
Date: 08-06-2015
DOI: 10.1093/NDT/GFV242
Abstract: Descriptions of inflammatory cells infiltrating the human kidney rarely mention B cells, other than in the specific scenario of transplantation. In these reports, B cells are localized almost exclusively within the kidney tubulointerstitium where they are ideally placed to interact with proximal tubule epithelial cells (PTEC). We have previously shown that activated PTEC down-modulate autologous T lymphocyte and dendritic cell function. In this report, we extend these prior studies to describe PTEC-B cell interactions. Stimulated B cells were cultured in the absence or presence of activated autologous human PTEC and monitored for proliferation, surface antigen expression, cytokine secretion and antibody (Ab) production. PTEC decreased B cell proliferative responses, whilst B cells cultured in the presence of PTEC displayed decreased levels of CD27, a marker of plasma B cells and memory cells. Interestingly, autologous PTEC also significantly decreased the number of B cells secreting both IgG and IgM and overall levels of Ab production. Transwell studies demonstrated that this modulation was primarily contact-dependent, and blocking studies with anti-PD-L1 led to partial restoration in Ab production. Further blocking studies targeting soluble HLA-G (sHLA-G) and IDO, two other immunoinhibitory molecules also up-regulated in our activated PTEC, demonstrated minor restoration of Ab responses. We report, for the first time, that PTEC are also able to modulate autologous B-cell phenotype and function via complex contact-dependent (PD-L1), soluble (sHLA-G) and intracellular (IDO) factors. We hypothesize that such mechanisms may have evolved to maintain peripheral immune-homeostasis, especially within the inflammatory milieu that exists within many kidney diseases.
Biofabrication of small diameter tissue-engineered vascular grafts
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.ACTBIO.2021.11.012
Abstract: Current clinical treatment strategies for the bypassing of small diameter (<6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue-engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo, promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current state-of-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future. STATEMENT OF SIGNIFICANCE: Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue-engineered vascular grafts.
Personalized Volumetric Tissue Generation by Enhancing Multiscale Mass Transport through 3D Printed Scaffolds in Perfused Bioreactors
Publisher: Wiley
Date: 08-07-2022
Abstract: Engineered tissues provide an alternative to graft material, circumventing the use of donor tissue such as autografts or allografts and non‐physiological synthetic implants. However, their lack of vasculature limits the growth of volumetric tissue more than several millimeters thick which limits their success post‐implantation. Perfused bioreactors enhance nutrient mass transport inside lab‐grown tissue but remain poorly customizable to support the culture of personalized implants. Here, a multiscale framework of computational fluid dynamics (CFD), additive manufacturing, and a perfusion bioreactor system are presented to engineer personalized volumetric tissue in the laboratory. First, microscale 3D printed scaffold pore geometries are designed and 3D printed to characterize media perfusion through CFD and experimental fluid testing rigs. Then, perfusion bioreactors are custom‐designed to combine 3D printed scaffolds with flow‐focusing inserts in patient‐specific shapes as simulated using macroscale CFD. Finally, these computationally optimized bioreactor‐scaffold assemblies are additively manufactured and cultured with pre‐osteoblast cells for 7, 20, and 24 days to achieve tissue growth in the shape of human calcaneus bones of 13 mL volume and 1 cm thickness. This framework enables an intelligent model‐based design of 3D printed scaffolds and perfusion bioreactors which enhances nutrient transport for long‐term volumetric tissue growth in personalized implant shapes. The novel methods described here are readily applicable for use with different cell types, biomaterials, and scaffold microstructures to research therapeutic solutions for a wide range of tissues.
Rational design and fabrication of multiphasic soft network composites for tissue engineering articular cartilage: A numerical model-based approach
Publisher: Elsevier BV
Date: 05-2018
In vitro and in vivo investigation of a zonal microstructured scaffold for osteochondral defect repair
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121548
Abstract: Articular cartilage is comprised of zones that vary in architecture, extracellular matrix composition, and mechanical properties. Here, we designed and engineered a porous zonal microstructured scaffold from a single biocompatible polymer (poly [ϵ-caprolactone]) using multiple fabrication strategies: electrospinning, spherical porogen leaching, directional freezing, and melt electrowriting. With this approach we mimicked the zonal structure of articular cartilage and produced a stiffness gradient through the scaffold which aligns with the mechanics of the native tissue. Chondrocyte-seeded scaffolds accumulated extracellular matrix including glycosaminoglycans and collagen II over four weeks in vitro. This prompted us to further study the repair efficacy in a skeletally mature porcine model. Two osteochondral lesions were produced in the trochlear groove of 12 animals and repaired using four treatment conditions: (1) microstructured scaffold, (2) chondrocyte seeded microstructured scaffold, (3) MaioRegen™, and (4) empty defect. After 6 months the defect sites were harvested and analyzed using histology, micro computed tomography, and Raman microspectroscopy mapping. Overall, the scaffolds were retained in the defect space, repair quality was repeatable, and there was clear evidence of osteointegration. The repair quality of the microstructured scaffolds was not superior to the control based on histological scoring however, the lower score was biased by the lack of histological staining due to the limited degradation of the implant at 6 months. Longer follow up studies (e.g., 1 yr) will be required to fully evaluate the efficacy of the microstructured scaffold. In conclusion, we found consistent scaffold retention, osteointegration, and prolonged degradation of the microstructured scaffold, which we propose may have beneficial effects for the long-term repair of osteochondral defects.
Formalin fixation affects equilibrium partitioning of an ionic contrast agent-microcomputed tomography (EPIC-μCT) imaging of osteochondral samples
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.
GelMA-glycol chitosan hydrogels for cartilage regeneration: The role of uniaxial mechanical stimulation in enhancing mechanical, adhesive, and biochemical properties
Publisher: AIP Publishing
Date: 09-2023
DOI: 10.1063/5.0160472
Bone Tissue Engineering
Publisher: WORLD SCIENTIFIC
Date: 12-2010
Osteoimmunomodulation for the development of advanced bone biomaterials
Publisher: Elsevier BV
Date: 07-2016
Characterisation of ovine bone marrow-derived stromal cells (oBMSC) and evaluation of chondrogenically induced micro-pellets for cartilage tissue repair in vivo
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2020
DOI: 10.1101/2020.05.15.094847
Abstract: Bone marrow stromal cells (BMSC) show promise in cartilage repair, and sheep are the most common large animal pre-clinical model. The objective of this study was to characterize ovine BMSC (oBMSC) in vitro , and to evaluate the capacity of chondrogenic micro -pellets manufactured from oBMSC or ovine articular chondrocytes (oACh) to repair osteochondral defects in sheep. oBMSC were characterised for surface marker expression using flow cytometry and evaluated for tri-lineage differentiation. oBMSC micro -pellets were manufactured in a microwell platform, and chondrogenesis was compared at 2%, 5%, and 20% O 2 . The capacity of cartilage micro -pellets manufactured from oBMSC or oACh to repair osteochondral defects in adult sheep was evaluated in an 8-week pilot study. Expanded oBMSC were positive for CD44 and CD146 and negative for CD45. The common adipogenic induction medium ingredient, 3-Isobutyl-1-methylxanthine (IBMX) was toxic to oBMSC, but adipogenesis could be restored by excluding IBMX from the medium. BMSC chondrogenesis was optimal in a 2% O 2 atmosphere. Micro -pellets formed from oBMSC or oACh appeared morphologically similar, but hypertrophic genes were elevated in oBMSC micro -pellets. While oACh micro -pellets formed cartilage-like repair tissue in sheep, oBMSC micro -pellets did not. The sensitivity of oBMSC to IBMX highlights species-species differences between oBMSC and hBMSC. Micro -pellets manufactured from oBMSC were not effective in repairing osteochondral defects, while oACh micro -pellets enabled modest repair. While oBMSC can be driven to form cartilage-like tissue in vitro, their effective use in cartilage repair will require mitigation of hypertrophy.
Additive manufacturing of tissues and organs
Publisher: Elsevier BV
Date: 08-2012
Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures
Publisher: Wiley
Date: 25-02-2014
DOI: 10.1002/BIT.25200
Abstract: Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury while recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, while maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size, and permeability decreased, while computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (∼ 45% to ∼ 86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment.
Effect of gelatin source and photoinitiator type on chondrocyte redifferentiation in gelatin methacryloyl-based tissue-engineered cartilage constructs
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8TB02607F
Abstract: This work investigates neocartilage formation in bovine and porcine gelatin methacryloyl-based hydrogels photocrosslinked using ultraviolet or visible light photoinitiator systems.
Micro-pellet culture reveals that bone marrow mesenchymal stromal cell (BMSC) chondrogenic induction is triggered by a single day of TGF-β1 exposure
Publisher: Cold Spring Harbor Laboratory
Date: 26-11-2019
DOI: 10.1101/853556
Abstract: Despite immense promise, engineering of stable cartilage tissue from bone marrow-derived stromal cells (BMSCs, also known as bone marrow-derived “mesenchymal stem cells”) remains elusive. Relative cartilage-like matrix deposition is commonly used to guide BMSC chondrogenic optimisation efforts. However, matrix deposition is heterogeneous in most models, and notably, it lags behind cell fate decisions. We reason that the lag time between cell fate decision and matrix accumulation, coupled with matrix heterogeneity, has obscured basic BMSC biological characteristics, such as differentiation kinetics. Here, we utilize a customized microwell platform to assemble hundreds of small-diameter BMSC micro -pellets and characterized chondrogenic differentiation kinetics in response to the canonical signaling molecule, transforming growth factor-β1 (TGF-β1). Micro -pellets provide a homogeneous readout, and our experimental design accounts for the significant time delay between growth factor signal and deposition of cartilage-like matrix. While 14-to-21-day induction protocols are routine, BMSC micro -pellet cultures reveal that a single day of TGF-β1 exposure was sufficient to trigger chondrogenic differentiation cascades resulting in outcomes similar to micro -pellets exposed to TGF-β1 for 21 days. RNA-sequencing analysis demonstrated that one day of TGF-β1 exposure was also sufficient to induce hypertrophic cascades in BMSC, not observed in articular chondrocytes. Refocusing chondrogenic induction optimisation efforts from weeks to the first hours or days of culture, using homogeneous model systems, may benefit efforts to build stable cartilage formed by BMSCs. The macro -pellet model, and assumptions generated using it, have permeated BMSC-based cartilage tissue engineering strategies since the 1990s. Using a micro -pellet model, we show that BMSC chondrogenic kinetics are significantly more rapid than historical macro -pellets data suggests, and that BMSC chondrogenic and hypertrophic commitment is instructed by a single day of TGF-β1 exposure. This highly relevant study demonstrates that: (1) macro -pellets, which are large heterogeneous tissue models confound the differentiation kinetics visible in micro -pellet models (2) induction strategies should focus on the first hours or days of culture (3) even a single day of TGF-β1 exposure drives BMSC to form hypertrophic tissue in vivo , requiring early intervention to prevent hypertrophy and (4) articular chondrocytes and BMSCs respond distinctly to TGF-β1.
Prioritizing Land and Sea Conservation Investments to Protect Coral Reefs
Publisher: Public Library of Science (PLoS)
Date: 30-08-2010
Strategies for zonal cartilage repair using hydrogels
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.
A Method for Prostate and Breast Cancer Cell Spheroid Cultures Using Gelatin Methacryloyl-Based Hydrogels
Publisher: Springer New York
Date: 2018
DOI: 10.1007/978-1-4939-7845-8_10
Abstract: Modern tissue engineering technologies have delivered tools to recreate a cell's naturally occurring niche in vitro and to investigate normal and pathological cell-cell and cell-niche interactions. Hydrogel biomaterials mimic crucial properties of native extracellular matrices, including mechanical support, cell adhesion sites and proteolytic degradability. As such, they are applied as 3D cell culture platforms to replicate tissue-like architectures observed in vivo, allowing physiologically relevant cell behaviors. Here we review bioengineered 3D approaches used for prostate and breast cancer. Furthermore, we describe the synthesis and use of gelatin methacryloyl-based hydrogels as in vitro 3D cancer model. This platform is used to engineer the microenvironments for prostate and breast cancer cells to study processes regulating spheroid formation, cell functions and responses to therapeutic compounds. Collectively, these bioengineered 3D approaches provide cell biologists with innovative pre-clinical tools that integrate the complexity of the disease seen in patients to advance our knowledge of cancer cell physiology and the contribution of a tumor's surrounding milieu.
Protective effects of reactive functional groups on chondrocytes in photocrosslinkable hydrogel systems
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.ACTBIO.2015.08.038
Abstract: Photocrosslinkable hydrogels are frequently used in cartilage tissue engineering, with crosslinking systems relying on cytotoxic photoinitiators and ultraviolet (UV) light to form permanent hydrogels. These systems are rarely assessed in terms of optimization of photoinitiator or UV dosage, with non-cytotoxic concentrations from literature deemed sufficient. We hypothesized that the number of reactive functional groups present within a hydrogel polymer is highly relevant when crosslinking, affording cytoprotection to chondrocytes by preferentially interacting with the highly reactive radicals that are formed during UV-mediated activation of a photoinitiator. This was tested using two photocrosslinkable hydrogel systems: gelatin methacrylamide (GelMA) and gellan gum methacrylate (GGMA). We further assessed the effects of two different UV dosages on chondrocyte differentiation while subject to a single photoinitiator dosage in the GGMA system. Most notably, we found that a higher ratio of reactive groups to photoinitiator molecules offers cytoprotective effects, and future developments in photocrosslinkable hydrogel technology may involve assessment of such ratios. In contrast, we found there to be no effect of UV on chondrocyte differentiation at the two chosen dosages. Overall the optimization of photocrosslinkable systems is of great value in cartilage tissue engineering and these data provide a groundwork for such concepts to be developed further. Photocrosslinkable hydrogels, which use photoinitiators and predominantly ultraviolet light to form stable matrices for cell encapsulation and tissue development, are promising for cartilage tissue engineering. While both photoinitiators and ultraviolet light can damage cells, these systems have generally not been optimized. We propose that the ratio of reactive functional groups within a polymer to photoinitiator molecules is a critical parameter for optimization of photocrosslinkable hydrogels. Using photocrosslinkable gelatin and gellan gum, we found that a higher ratio of reactive groups to photoinitiator molecules protected chondrocytes, but did not affect chondrocyte differentiation. The principle of cytoprotection by functional groups developed in this work will be of great value in optimizing photocrosslinkable hydrogel systems for cartilage and other tissue engineering applications.
Influence of osteocytes in the in vitro and in vivo β-tricalcium phosphate-stimulated osteogenesis
Publisher: Wiley
Date: 30-09-2014
DOI: 10.1002/JBM.A.34954
Abstract: Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the β-tricalcium phosphate (β-TCP) stimulated osteogenesis. It was found that osteocytes responded to the β-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of β-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials.
Making talk work: Using a dialogic approach to develop intercultural competence with students at an Australian university
Publisher: Informa UK Limited
Date: 15-02-2022
Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.BIOMATERIALS.2013.11.014
Abstract: Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used β-tricalcium phosphate (β-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to β-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the β-TCP stimulation, indicating that macrophage may participate in the β-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned β-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials.
A new mechanical indentation framework for functional assessment of articular cartilage
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.JMBBM.2018.02.028
Abstract: The conventional mechanical properties of articular cartilage, such as compressive stiffness, have been shown to have limited capacity to distinguish visually normal from degraded cartilage s les. In this study, a new mechanical indentation framework for assessing functional properties of articular cartilage during loading/unloading, i.e. deformation and recovery, was established. The capacity of a ring-shaped indenter integrated with an ultrasound transducer to distinguish mechanically intact from proteoglycan-depleted tissue was investigated. To achieve this, normal and enzymatically degraded bovine osteochondral s les were subjected to loading/unloading while the response of the tissue at the middle was captured by ultrasound at the same time. The enzymatic degradation model was characterized by amount of proteoglycan content, glycosaminoglycan release and proteomic analysis. The mechanical response of a wider continuum of articular cartilage in the loaded area and its surrounding region was captured in this framework leading to investigate two parameters, L and TS, related to the surrounding tissue of the loaded area for functional assessment of cartilage. L is the distance between the ultrasound transducer and articular cartilage surface and TS is the transient strain of articular cartilage during loading and unloading. Classification Analysis based on Principal Component Analysis was used to investigate the capacity of the new parameters to assess the functionality of the tissue. Multivariate statistics based on Partial Least Squares regression was employed to identify the correlation between the response of the tissue in the indented area and its surrounding cartilage. The results of this study indicate that L during loading (deformation) can differentiate normal and mildly proteoglycan-depleted s les from severely depleted s les and L during unloading (recovery) can distinguish between normal and proteoglycan-depleted tissue. However, TS during deformation and recovery is unable to discriminate normal cartilage s les from proteoglycan-depleted tissue. The results also demonstrate a strong correlation between mechanical properties of the loaded area with the response of its surrounding cartilage during recovery. It is therefore concluded that L in this newly established framework can discriminate between normal and proteoglycan-depleted cartilage s les. However, more s les will be needed to verify the demarcation between s les degraded for varying amount of time.
The Roles of Hypoxia in theIn VitroEngineering of Tissues
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.
Perspectives in Multiphasic Osteochondral Tissue Engineering
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.
Challenges in engineering large customized bone constructs
Publisher: Wiley
Date: 09-02-2017
DOI: 10.1002/BIT.26222
Abstract: The ability to treat large tissue defects with customized, patient-specific scaffolds is one of the most exciting applications in the tissue engineering field. While an increasing number of modestly sized tissue engineering solutions are making the transition to clinical use, successfully scaling up to large scaffolds with customized geometry is proving to be a considerable challenge. Managing often conflicting requirements of cell placement, structural integrity, and a hydrodynamic environment supportive of cell culture throughout the entire thickness of the scaffold has driven the continued development of many techniques used in the production, culturing, and characterization of these scaffolds. This review explores a range of technologies and methods relevant to the design and manufacture of large, anatomically accurate tissue-engineered scaffolds with a focus on the interaction of manufactured scaffolds with the dynamic tissue culture fluid environment. Biotechnol. Bioeng. 2017 : 1129-1139. © 2016 Wiley Periodicals, Inc.
Tissue Engineering of Articular Cartilage with Biomimetic Zones
Publisher: Mary Ann Liebert Inc
Date: 06-2009
Hyaluronic Acid Enhances the Mechanical Properties of Tissue-Engineered Cartilage Constructs
Publisher: Public Library of Science (PLoS)
Date: 12-2014
Functionalization, preparation and use of cell-laden gelatin methacryloyl-based hydrogels as modular tissue culture platforms
Publisher: Springer Science and Business Media LLC
Date: 17-03-2016
Abstract: Progress in advancing a system-level understanding of the complexity of human tissue development and regeneration is h ered by a lack of biological model systems that recapitulate key aspects of these processes in a physiological context. Hence, growing demand by cell biologists for organ-specific extracellular mimics has led to the development of a plethora of 3D cell culture assays based on natural and synthetic matrices. We developed a physiological microenvironment of semisynthetic origin, called gelatin methacryloyl (GelMA)-based hydrogels, which combine the biocompatibility of natural matrices with the reproducibility, stability and modularity of synthetic biomaterials. We describe here a step-by-step protocol for the preparation of the GelMA polymer, which takes 1-2 weeks to complete, and which can be used to prepare hydrogel-based 3D cell culture models for cancer and stem cell research, as well as for tissue engineering applications. We also describe quality control and validation procedures, including how to assess the degree of GelMA functionalization and mechanical properties, to ensure reproducibility in experimental and animal studies.
Multiphasic construct studied in an ectopic osteochondral defect model
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.
Related Organisations
University Of California, San Diego
Location: United States of America
Related Funding Activities
Discovery Projects - Grant ID: DP110103543
Start Date: 2011
End Date: 06-2017
Amount: $210,000.00
Funder: Australian Research Council
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Start Date: 2008
End Date: 12-2010
Amount: $563,933.00
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View Funded ActivityDiscovery Projects - Grant ID: DP180103009
Start Date: 06-2018
End Date: 12-2021
Amount: $392,834.00
Funder: Australian Research Council
View Funded ActivityARC Future Fellowships - Grant ID: FT110100166
Start Date: 05-2012
End Date: 06-2017
Amount: $639,288.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Training Centres - Grant ID: IC190100020
Start Date: 08-2020
End Date: 08-2025
Amount: $3,998,796.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Training Centres - Grant ID: IC190100026
Start Date: 01-2021
End Date: 11-2027
Amount: $4,969,663.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE170100057
Start Date: 09-2017
End Date: 09-2018
Amount: $250,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP220100452
Start Date: 10-2022
End Date: 10-2025
Amount: $449,000.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Training Centres - Grant ID: IC160100026
Start Date: 03-2017
End Date: 09-2021
Amount: $3,722,989.00
Funder: Australian Research Council
View Funded Activity