title: Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model.
abstract: Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel for cartilage repair obtained by covalently grafting poly(N-isopropylacrylamide) to hyaluronan, to give a brush co-polymer HpN. The gel is fluid at room temperature and becomes gel at body temperature. In this pilot study HpN safety and repair response were evaluated in an osteochondral defect model in rabbit. Follow-up was of 1 week and 12 weeks and the empty defect served as a control, for a total of four experimental groups. At 12 weeks the defect sites were evaluated macroscopically and histologically. Local lymph nodes, spleen, liver, and kidneys were analyzed for histopathological evaluation. HpN could be easily injected and remained into the defect throughout the study. The macroscopic score was statistically superior for HpN versus empty. Histological score gave opposite trend but not statistically significant. A slight tissue reaction was observed around HpN, however, vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with fairly 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 conclusion, HpN is easily injectable, remains into an osteochondral defect within a moving synovial joint, is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1469-1478, 2016.
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Este
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Christoph Martin
authors.initials: CM
authors.lastname: Sprecher
authors.affiliation: Department of Anatomy II-Neuroanatomy, Ludwig-Maximilian-University of Munich, Bavaria, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Milz
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Nehrbass
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Iska
authors.initials: I
authors.lastname: Dresing
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zeiter
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, 7270, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Eglin
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology; D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004548:Elasticity; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D011817:Rabbits; D012212:Rheology; D013696:Temperature; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; C052970:poly-N-isopropylacrylamide; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid
keywords: biocompatibility; cartilage repair; hyaluronan; thermoresponsive hydrogel