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基于透明质酸的互穿网络水凝胶作为用于髓核修复的细胞载体

Hyaluronic acid-based interpenetrating network hydrogel as a cell carrier for nucleus pulposus repair.

作者信息

Guo Wei, Douma Luzia, Hu Ming Hsien, Eglin David, Alini Mauro, Šećerović Amra, Grad Sibylle, Peng Xinsheng, Zou Xuenong, D'Este Matteo, Peroglio Marianna

机构信息

AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland; Department of Spinal Surgery, Orthopaedic Research Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China.

AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, Switzerland.

出版信息

Carbohydr Polym. 2022 Feb 1;277:118828. doi: 10.1016/j.carbpol.2021.118828. Epub 2021 Oct 29.

DOI:10.1016/j.carbpol.2021.118828
PMID:34893245
Abstract

Hyaluronic acid (HA) is a key component of the intervertebral disc (IVD) that is widely investigated as an IVD biomaterial. One persisting challenge is introducing materials capable of supporting cell encapsulation and function, yet with sufficient mechanical stability. In this study, a hybrid interpenetrating polymer network (IPN) was produced as a non-covalent hydrogel, based on a covalently cross-linked HA (HA-BDDE) and HA-poly(N-isopropylacrylamide) (HA-pNIPAM). The hybrid IPN was investigated for its physicochemical properties, with histology and gene expression analysis to determine matrix deposition in vitro and in an ex vivo model. The IPN hydrogel displayed cohesiveness for at least one week and rheological properties resembling native nucleus pulposus (NP) tissue. When implanted in an ex vivo IVD organ culture model, the IPN supported cell viability, phenotype expression of encapsulated NP cells and IVD matrix production over four weeks under physiological loading. Overall, our results indicate the therapeutic potential of this HA-based IPN hydrogel for IVD regeneration.

摘要

透明质酸(HA)是椎间盘(IVD)的关键成分,作为一种IVD生物材料受到广泛研究。一个持续存在的挑战是引入能够支持细胞包封和功能,同时具有足够机械稳定性的材料。在本研究中,基于共价交联的HA(HA-BDDE)和HA-聚(N-异丙基丙烯酰胺)(HA-pNIPAM)制备了一种作为非共价水凝胶的混合互穿聚合物网络(IPN)。对该混合IPN的物理化学性质进行了研究,并通过组织学和基因表达分析来确定其在体外和离体模型中的基质沉积情况。IPN水凝胶至少一周内表现出粘性,其流变学性质类似于天然髓核(NP)组织。当植入离体IVD器官培养模型时,在生理负荷下,IPN在四周内支持细胞活力、包封NP细胞的表型表达以及IVD基质生成。总体而言,我们的结果表明这种基于HA的IPN水凝胶在IVD再生方面具有治疗潜力。

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