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用于软骨手术和修复的合成聚乙烯醇基膜。

Synthetic Poly(Vinylalcohol)-Based Membranes for Cartilage Surgery and Repair.

机构信息

Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, Singapore 138669, Singapore.

出版信息

Biotechnol J. 2017 Dec;12(12). doi: 10.1002/biot.201700134. Epub 2017 Sep 25.

Abstract

Cell-based therapies for cartilage repair are continually being developed to treat osteoarthritis. The cells are either introduced directly by intra-articular injection or via a cell-seeded matrix scaffold. Here, poly(vinylalcohol)-based membranes are developed to be used for mesenchymal stem cell implantation in cartilage repair procedures, having controllable physicochemical properties such as porosity, mechanical strength, and permeability, and a unique self-sealing property. The membranes possess a bilayer structure with a less porous layer providing mechanical strength and selective permeability, exhibit an elastic modulus of between 0.3 and 0.9 MPa, and are permeable to molecules <40 kDa, which is in the range of cartilage permeability. Three different peptide ligands with the sequences Ac-GCGYGRGDSPG, Ac-GCG(OPG)4REGOFG(OPG)4, and Ac-GCG(OPG)7, respectively, are conjugated to the membranes and subject to in vitro cell adhesion and differentiation assays. Col I/Col II gene expression ratios indicated that the collagen-mimetic peptide, Ac-GCG(OPG)7, best supported mesenchymal stem cell differentiation into the chondrogenic lineage. Although low retention of the membrane is observed in vivo in a rabbit knee model, results suggest that the membrane was able to facilitate mesenchymal stem cell implantation and differentiation to chondrocytes. These PVA-based membranes provide a feasible, synthetic, off-the-shelf material for the delivery of stem cells, and can be modified for other surgical applications.

摘要

用于软骨修复的基于细胞的疗法不断被开发出来以治疗骨关节炎。这些细胞可以通过关节内注射直接引入,也可以通过细胞接种的基质支架引入。本文开发了基于聚乙烯醇的膜,用于软骨修复过程中的间充质干细胞植入,具有可控制的物理化学性质,如孔隙率、机械强度和渗透性,以及独特的自密封特性。该膜具有双层结构,较不多孔的层提供机械强度和选择性渗透性,其弹性模量在 0.3 至 0.9 MPa 之间,并且对 <40 kDa 的分子具有渗透性,这在软骨渗透性范围内。分别将三个具有序列 Ac-GCGYGRGDSPG、Ac-GCG(OPG)4REGOFG(OPG)4 和 Ac-GCG(OPG)7 的不同肽配体共轭到膜上,并进行体外细胞黏附和分化测定。Col I/Col II 基因表达比值表明,胶原模拟肽 Ac-GCG(OPG)7 最能支持间充质干细胞向软骨细胞分化。尽管在兔膝关节模型中体内观察到膜的低保留率,但结果表明该膜能够促进间充质干细胞的植入和向软骨细胞的分化。这些基于 PVA 的膜为干细胞的输送提供了一种可行的、合成的、现成的材料,并且可以针对其他手术应用进行修改。

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