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- W2337489181 abstract "Event Abstract Back to Event Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model Matteo D'Este1*, Christoph Sprecher1*, Stefan Milz2*, Dirk Nehrbass1, Iska Dresing1, Stephan Zeiter1*, Mauro Alini1* and David Eglin1* 1 AO Research Institute Davos, Musculoskeletal Regeneration, Switzerland 2 Ludwig-Maximilian-University of Munich, Department of Anatomy II – Neuroanatomy, Germany Introduction: Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel (THH) for cartilage repair. The gel is fluid at room temperature and becomes gel at body temperature. THH was obtained by covalently grafting poly(N-isopropylacrylamide) (pNIPAM) to hyaluronan. In this pilot study THH safety and repair response were evaluated in an osteochondral defect model in rabbit. Materials and Methods: THH was prepared and characterized as previously reported[1]. The in vivo study protocol was approved by the local authorities. Skeletally mature (> 24 weeks) female New Zealand White rabbits (Charles River), weighing 3.8 ± 0.3 kg were enrolled in the study. A defect of 2.7 mm diameter and 4 mm depth was drilled in the central area of the medial trochlear ridge. Experimental groups were: empty 1 week (n=4); THH 1 week (n=4); empty 12 weeks (n=6) and THH 12 weeks (n=6). At 12 weeks the defect sites were evaluated macroscopically according to the ICRS Cartilage Repair Assessment System and histologically with the O'Driscoll score system in hematoxylin/eosin and safranin O fast green stained sections. At week 1 and 12, samples from joint capsule, proximal lymph nodes, spleen, liver and kidneys were analysed for histopathological evaluation. Results: THH could be easily injected and remained within the defect throughout the study. The ICRS score showed a statistically superior outcome for THH in comparison to the empty control. O'Driscoll score gave opposite trend without reaching statistical significance (Table 1). A slight tissue reaction was observed around THH, however vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with relatively good continuity and lateral integration into the existing articular cartilage was observed in all cases (fig 2). For the empty group bone formation above the tidemark was observed (* in fig 2). No signs of local or systemic acute or subacute toxicity were observed in any of the harvested tissues. Table 1 – Macroscopic ICRS Score and O'Driscoll Score average values, maximum and minimum values of empty and HpN group at 12 weeks Fig. 1: Overviews of the osteochondral defect in histological sections stained with Hematoxylin and Eosin (a, b) Safranin O Fast Green (c, d) at 12 weeks. The borders of the defects are marked with top down arrows. Empty group: panels a, c. (*) indicates new bone formation above the level of the original tidemark (dashed line). Scale bar = 1 mm for all images. Discussion: THH was both easily injectable and not dislocated from the defect in a moving joint. The empty control achieved relatively high tissue repair. Therefore a wider or less deep defect would have been more appropriate. pNIPAM toxicity was a potential concern, however histopathology showed no signs of local or systemic acute or subacute toxicity. Conclusion: THH is easily injectable and remains into an osteochondral defect within a moving synovial joint. THH is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model and could therefore be a suitable cell or drug carrier for osteochondral repair. References:[1] M. D’Este, D. Eglin, M. Alini (2012) Carb Polym 90: 1378– 1385. Keywords: Hydrogel, Tissue Regeneration, Smart material, stimuli-response Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in musculoskeletal orthopeadics and tissues Citation: D'Este M, Sprecher C, Milz S, Nehrbass D, Dresing I, Zeiter S, Alini M and Eglin D (2016). Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01973 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Matteo D'Este, AO Research Institute Davos, Musculoskeletal Regeneration, Davos Platz, Switzerland, Email1 Dr. Christoph Sprecher, AO Research Institute Davos, Musculoskeletal Regeneration, Davos Platz, Switzerland, christoph.sprecher@aofoundation.org Dr. Stefan Milz, Ludwig-Maximilian-University of Munich, Department of Anatomy II – Neuroanatomy, Munich, Germany, stefan.milz@med.uni-muenchen.de Dr. Stephan Zeiter, AO Research Institute Davos, Musculoskeletal Regeneration, Davos Platz, Switzerland, stephan.zeiter@aofoundation.org Dr. Mauro Alini, AO Research Institute Davos, Musculoskeletal Regeneration, Davos Platz, Switzerland, mauro.alini@aofoundation.org Dr. David Eglin, AO Research Institute Davos, Musculoskeletal Regeneration, Davos Platz, Switzerland, david.eglin@aofoundation.org Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Matteo D'Este Christoph Sprecher Stefan Milz Dirk Nehrbass Iska Dresing Stephan Zeiter Mauro Alini David Eglin Google Matteo D'Este Christoph Sprecher Stefan Milz Dirk Nehrbass Iska Dresing Stephan Zeiter Mauro Alini David Eglin Google Scholar Matteo D'Este Christoph Sprecher Stefan Milz Dirk Nehrbass Iska Dresing Stephan Zeiter Mauro Alini David Eglin PubMed Matteo D'Este Christoph Sprecher Stefan Milz Dirk Nehrbass Iska Dresing Stephan Zeiter Mauro Alini David Eglin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page." @default.
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