一种具有蛋白聚糖样分级结构的可注射水凝胶可支持软骨细胞的输送和软骨生成。

An injectable hydrogel having proteoglycan-like hierarchical structure supports chondrocytes delivery and chondrogenesis.

机构信息

Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, Sector 81, Mohali, Punjab 140306, India.

Division of Endocrinology and Centre for Research in ASTHI, CSIR-Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226031, U.P., India.

出版信息

Int J Biol Macromol. 2021 Nov 1;190:474-486. doi: 10.1016/j.ijbiomac.2021.08.226. Epub 2021 Sep 8.

Abstract

The ECM of cartilage is composed of proteoglycans (PG) that contain glycosaminoglycan (GAG), aggrecan, hyaluronic acid (HA) and other molecular components which play an important role in regulating chondrocyte functions via cell-matrix interactions, integrin-mediated signalling etc. Implantation of chondrocytes encapsulated in scaffolds that mimic the micro-architecture of proteoglycan, is expected to enhance cartilage repair. With an aim to create a hydrogel having macromolecular structure that resembles the cartilage-specific ECM, we constructed a hierarchal structure that mimic the PG. The bottle brush structure of the aggrecan was obtained using chondroitin sulphate and carboxymethyl cellulose which served as GAG and core protein mimic respectively. A proteoglycan-like structure was obtained by cross-linking it with modified chitosan that served as a HA substitute. The physico-chemical characteristics of the above cross-linked injectable hydrogel supported long term human articular chondrocyte subsistence and excellent post-injection viability. The chondrocytes encapsulated in the PMH expressed significant levels of articular cartilage specific markers like collagen II, aggrecan, GAGs etc., indicating the ability of the hydrogel to support chondrocyte differentiation. The biocompatibility and biodegradability of the hydrogels was confirmed using suitable in vivo studies. The results revealed that the PG-mimetic hydrogel could serve as a promising scaffold for chondrocyte implantation.

摘要

软骨细胞外基质(ECM)由含有糖胺聚糖(GAG)的蛋白聚糖(PG)组成,聚集蛋白聚糖、透明质酸(HA)和其他分子成分通过细胞-基质相互作用、整合素介导的信号传导等方式在调节软骨细胞功能方面发挥着重要作用。通过模仿蛋白聚糖微结构的支架来包封软骨细胞的植入,有望增强软骨修复。为了创建具有类似于软骨细胞外基质的高分子结构的水凝胶,我们构建了一种模仿 PG 的层次结构。使用硫酸软骨素和羧甲基纤维素作为 GAG 和核心蛋白模拟物,获得了聚集蛋白聚糖的瓶刷结构。通过用作为 HA 替代品的改性壳聚糖交联,获得了类似蛋白聚糖的结构。上述交联可注射水凝胶的物理化学特性支持长期人类关节软骨细胞的存活和出色的注射后活力。包封在 PMH 中的软骨细胞表达了显著水平的关节软骨特异性标志物,如胶原 II、聚集蛋白聚糖、GAG 等,表明水凝胶具有支持软骨细胞分化的能力。通过适当的体内研究证实了水凝胶的生物相容性和可生物降解性。结果表明,PG 模拟水凝胶可用作软骨细胞植入的有前途的支架。

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