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Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model

Tuesday (09.05.2017)
16:10 - 16:30
Part of:


The self-healing capability of articular cartilage is inadequate, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel (THH) for cartilage repair. THH is an easily injectable fluid at room temperature and stiffens to become a viscoelastic gel at body temperature. In this pilot study THH safety and repair response were evaluated in an osteochondral defect model in rabbit.



THH was obtained by covalently grafting poly(N-isopropylacrylamide) (pNIPAM) to hyaluronan [1]. After approval by the local authorities, a defect of 2.7 mm was drilled in the central area of the medial trochlear ridge of skeletally mature New Zeeland rabbits. 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 (ICRS score) and histologically (O'Driscoll score) in hematoxylin/eosin and safranin O fast green stained sections. At week 1 and 12, samples or relevant organs underwent histopathological evaluation.



THH could be easily injected and remained within the defect throughout the study. The ICRS score showed a statistically superior outcome for THH (11.1/12) in comparison to the empty control (9.8/12). O'Driscoll score gave opposite trend (16.7/24 vs 18/24, respectively) without reaching statistical significance. A slight tissue reaction was observed around THH. An upper proteoglycans rich fibro-cartilaginous tissue with relatively good continuity and lateral integration into the existing articular cartilage was observed in all cases. No signs of local or systemic acute or subacute toxicity were observed in any of the harvested tissues.



THH was both easily injectable and not dislocated from the defect in a moving joint. pNIPAM toxicity was a potential concern, however histopathology showed no signs of local or systemic acute or subacute toxicity.



THH is easily injectable and remains into an osteochondral defect within a moving synovial joint. THH is biocompatible and chodropermissive in a rabbit model and could therefore be a suitable cell or drug carrier for osteochondral repair.



[1] M. D’Este et al, Carb Polym 90: 1378– 1385.

Dr. David Eglin
AO Foundation
Additional Authors:
  • Dr. Christoph Martin Sprecher
    AO Research Institute Davos
  • Prof. Stefan Milz
    Ludwig-Maximilian-University of Munich
  • Dr. Dirk Nehrbass
    AO Research Institute Davos
  • Iska Dresing
    AO Research Institute Davos
  • Dr. Stephan Zeiter
    AO Research Institute Davos
  • Prof. Dr. Mauro Alini
    AO Research Institute Davos
  • Dr. David Eglin
    AO Research Institute Davos