Visible-light-initiated hydrogels preserving cartilage extracellular signaling for inducing chondrogenesis of mesenchymal stem cells

Visible-light-initiated hydrogels preserving cartilage extracellular signaling for inducing chondrogenesis of mesenchymal stem cells
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DOI:
10.1016/j.actbio.2014.10.013
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发表时间:
2015-01-15
期刊:
影响因子:
9.7
通讯作者:
Lee, Min
Lee, Min
中科院分区:
工程技术1区
文献类型:
--
作者:
Choi, Bogyu;Kim, Soyon;Lee, Min

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水凝胶有一个独特的机会,通过在类似于关节软骨的高度肿胀的环境中引入间充质干细胞(MSC)来再生受损的软骨组织。在软骨发育过程中,胶原-细胞相互作用在转化生长因子-β 1(TGF-β 1)刺激下介导早期间充质凝聚和软骨形成中发挥重要作用。在这里,水凝胶环境,可以增强细胞-基质的相互作用和软骨形成稳定的II型胶原蛋白(Col II)和TGF-β 1到光聚合(甲基丙烯酸酯化)壳聚糖(MeGC)与简单的截留和亲和结合证明。MeGC水凝胶被设计成在核黄素(一种来自天然维生素的水性引发剂)存在下通过暴露于可见蓝光引发时胶凝。将Col II掺入MeGC水凝胶中增加了包囊软骨细胞对软骨细胞外基质的细胞凝聚和沉积。含有Col II的MeGC水凝胶支持TGF-β 1在软骨形成培养基中以受控方式随时间释放,并且掺入的TGF-β 1进一步增强了包封的软骨细胞和MSC,特别是滑膜MSC的软骨形成。与对照组相比,皮下植入水凝胶培养物显示在加载有TGF-β 1的构建体中大大改善了新软骨形成。这些发现表明软骨模拟水凝胶具有很高的软骨修复潜力。(C)2014 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Hydrogels have a unique opportunity to regenerate damaged cartilage tissues by introducing mesenchymal stem cells (MSCs) in a highly swollen environment similar to articular cartilage. During cartilage development, collagen-cell interactions play an important role in mediating early mesenchymal condensation and chondrogenesis with transforming growth factor-beta 1 (TGF-beta 1) stimulation. Here, a hydrogel environment that can enhance cell-matrix interactions and chondrogenesis by stabilizing type-II collagen (Col II) and TGF-beta 1 into photopolymerizable (methacrylated) chitosan (MeGC) with simple entrapment and affinity binding is demonstrated. The MeGC hydrogel was designed to gel upon initiation by exposure to visible blue light in the presence of riboflavin, an aqueous initiator from natural vitamin. The incorporation of Col II into MeGC hydrogels increased cellular condensation and deposition of cartilaginous extracellular matrix by encapsulated chondrocytes. MeGC hydrogels containing Col II supported the release of TGF-beta 1 in a controlled manner over time in chondrogenic medium and the incorporated TGF-beta 1 further enhanced chondrogenesis of encapsulated chondrocytes and MSCs, especially synovial MSCs. Subcutaneous implantation of hydrogel cultures showed greatly improved neocartilage formation in constructs loaded with TGF-beta 1 compared with controls. These findings suggest that cartilage mimetic hydrogels have a high potential for cartilage repair. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.