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用于修复骨软骨缺损的硅烷化壳聚糖和纤维素自固化水凝胶:从表征到犬类临床前评估

A Self-Setting Hydrogel of Silylated Chitosan and Cellulose for the Repair of Osteochondral Defects: From Characterization to Preclinical Evaluation in Dogs.

作者信息

Boyer Cécile, Réthoré Gildas, Weiss Pierre, d'Arros Cyril, Lesoeur Julie, Vinatier Claire, Halgand Boris, Geffroy Olivier, Fusellier Marion, Vaillant Gildas, Roy Patrice, Gauthier Olivier, Guicheux Jérôme

机构信息

Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, France.

Université de Nantes, UFR Odontologie, Nantes, France.

出版信息

Front Bioeng Biotechnol. 2020 Jan 29;8:23. doi: 10.3389/fbioe.2020.00023. eCollection 2020.

Abstract

Articular cartilage (AC) may be affected by many injuries including traumatic lesions that predispose to osteoarthritis. Currently there is no efficient cure for cartilage lesions. In that respect, new strategies for regenerating AC are contemplated with interest. In this context, we aim to develop and characterize an injectable, self-hardening, mechanically reinforced hydrogel (Si-HPCH) composed of silanised hydroxypropymethyl cellulose (Si-HPMC) mixed with silanised chitosan. The cytocompatibility of Si-HPCH was tested using human adipose stromal cells (hASC). , we first mixed Si-HPCH with hASC to observe cell viability after implantation in nude mice subcutis. Si-HPCH associated or not with canine ASC (cASC), was then tested for the repair of osteochondral defects in canine femoral condyles. Our data demonstrated that Si-HPCH supports hASC viability in culture. Moreover, Si-HPCH allows the transplantation of hASC in the subcutis of nude mice while maintaining their viability and secretory activity. In the canine osteochondral defect model, while the empty defects were only partially filled with a fibrous tissue, defects filled with Si-HPCH with or without cASC, revealed a significant osteochondral regeneration. To conclude, Si-HPCH is an injectable, self-setting and cytocompatible hydrogel able to support the and viability and activity of hASC as well as the regeneration of osteochondral defects in dogs when implanted alone or with ASC.

摘要

关节软骨(AC)可能受到多种损伤影响,包括易引发骨关节炎的创伤性损伤。目前,对于软骨损伤尚无有效的治愈方法。在这方面,人们对再生AC的新策略颇感兴趣。在此背景下,我们旨在研发并表征一种由硅烷化羟丙基甲基纤维素(Si-HPMC)与硅烷化壳聚糖混合而成的可注射、自硬化、机械增强水凝胶(Si-HPCH)。使用人脂肪基质细胞(hASC)测试了Si-HPCH的细胞相容性。首先,我们将Si-HPCH与hASC混合,以观察植入裸鼠皮下后的细胞活力。然后,测试了与犬脂肪干细胞(cASC)结合或未结合的Si-HPCH对犬股骨髁骨软骨缺损的修复效果。我们的数据表明,Si-HPCH在培养中支持hASC的活力。此外,Si-HPCH允许将hASC移植到裸鼠皮下,同时保持其活力和分泌活性。在犬骨软骨缺损模型中,空缺损仅部分被纤维组织填充,而填充有Si-HPCH(有无cASC)的缺损则显示出明显的骨软骨再生。总之,Si-HPCH是一种可注射、自固化且细胞相容的水凝胶,当单独植入或与ASC一起植入时,能够支持hASC的活力和活性以及犬骨软骨缺损的再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef42/7025592/4970a60ec380/fbioe-08-00023-g001.jpg

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