Bardsley, K., Kwarciak, A., Freeman, C. et al. (3 more authors) (2017) Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes. Biomaterials, 112. pp. 313-323. ISSN 0142-9612
Abstract
The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5–10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6 fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31–45 μm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed. Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume compared to 7.01% in the control defects. Development of tissue engineered hypertrophic cartilage to use as a bone graft substitute is an exciting development in regenerative medicine. This is a proof of principal study demonstrating the potential of nasal chondrocytes to engineer hypertrophic cartilage which will remodel into bone on in vivo transplantation. This approach to making engineered hypertrophic cartilage grafts could form the basis of a new potential future clinical treatment for maxillofacial reconstruction.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Elsevier. This is an author produced version of a paper subsequently published in Biomaterials. Uploaded in accordance with the publisher's self-archiving policy. Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Bone tissue engineering; Nasal chondrocytes; Bone graft; Hypertrophic cartilage; Bone regeneration; Maxillofacial reconstruction |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number EUROPEAN COMMISSION - FP6/FP7 NBC-REGEN4 - 302315 EUROPEAN COMMISSION - FP6/FP7 MICARTREGEN-GA-2013-627480 CERAMISYS UNSPECIFIED ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL (EPSRC) UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Nov 2016 16:48 |
Last Modified: | 29 Mar 2018 09:17 |
Published Version: | https://doi.org/10.1016/j.biomaterials.2016.10.014 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.biomaterials.2016.10.014 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107327 |
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