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基于改性壳聚糖和丝素蛋白并添加脱细胞软骨细胞外基质的可注射仿生水凝胶用于软骨修复与再生

Injectable biomimetic hydrogel based on modified chitosan and silk fibroin with decellularized cartilage extracellular matrix for cartilage repair and regeneration.

作者信息

Wan Jinpeng, Jiang Jinshan, Yu Xinyi, Zhou Jie, Wang Yukang, Fu Shuang, Wang Jie, Liu Yufei, Dong Yunsheng, Midgley Adam C, Wang Shufang

机构信息

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Weijin Road 94th, Tianjin 300071, PR China.

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Weijin Road 94th, Tianjin 300071, PR China.

出版信息

Int J Biol Macromol. 2025 Apr;298:140058. doi: 10.1016/j.ijbiomac.2025.140058. Epub 2025 Jan 18.

Abstract

Cartilage defect repair remains a challenge for clinicians due to the limited self-healing capabilities of cartilage. Microenvironment-specific biomimetic hydrogels have shown great potential in cartilage regeneration because of their excellent biological properties. In this study, a hydrogel system consisting of p-hydroxybenzene propanoic acid-modified chitosan (PC), silk fibroin (SF) and decellularized cartilage extracellular matrix (DCM) was prepared. Under the catalysis of horseradish peroxidase (HRP), the phenol hydroxyl groups on PC and SF were crosslinked to form a hydrogel. DCM incorporation into the hydrogel facilitated an emulation of the natural cartilage extracellular matrix. The synthesized injectable hydrogels could fill irregular defects and formed network structures that promoted cell adhesion and proliferation. In vitro experiments demonstrated that the hydrogels had biocompatibility and promoted chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The DCM-derived hydrogel exhibited low immunogenicity in vivo, and in the treatment of both rabbit trochlear groove cartilage defects and goat femoral condyle cartilage defects, the hydrogel accelerated the cartilage regeneration. In summary, our developed composite hydrogel system in the study offers a potential strategy for the effective repair of cartilage defects.

摘要

由于软骨自身修复能力有限,软骨缺损修复仍是临床医生面临的一项挑战。特定微环境的仿生水凝胶因其优异的生物学特性,在软骨再生方面显示出巨大潜力。在本研究中,制备了一种由对羟基苯丙酸修饰的壳聚糖(PC)、丝素蛋白(SF)和脱细胞软骨细胞外基质(DCM)组成的水凝胶体系。在辣根过氧化物酶(HRP)催化下,PC和SF上的酚羟基交联形成水凝胶。将DCM掺入水凝胶有助于模拟天然软骨细胞外基质。合成的可注射水凝胶能够填充不规则缺损,并形成促进细胞黏附和增殖的网络结构。体外实验表明,该水凝胶具有生物相容性,并能促进骨髓间充质干细胞(BMSC)向软骨细胞分化。源自DCM的水凝胶在体内表现出低免疫原性,在治疗兔滑车沟软骨缺损和山羊股骨髁软骨缺损时,该水凝胶均加速了软骨再生。总之,本研究中开发的复合水凝胶体系为有效修复软骨缺损提供了一种潜在策略。

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