Lin Hang, Cheng Anthony Wai-Ming, Alexander Peter G, Beck Angela M, Tuan Rocky S
1 Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania.
Tissue Eng Part A. 2014 Sep;20(17-18):2402-11. doi: 10.1089/ten.TEA.2013.0642. Epub 2014 Apr 9.
Chondroprogenitor cells encapsulated in a chondrogenically supportive, three-dimensional hydrogel scaffold represents a promising, regenerative approach to articular cartilage repair. In this study, we have developed an injectable, biodegradable methacrylated gelatin (mGL)-based hydrogel capable of rapid gelation via visible light (VL)-activated crosslinking in air or aqueous solution. The mild photocrosslinking conditions permitted the incorporation of cells during the gelation process. Encapsulated human-bone-marrow-derived mesenchymal stem cells (hBMSCs) showed high, long-term viability (up to 90 days) throughout the scaffold. To assess the applicability of the mGL hydrogel for cartilage tissue engineering, we have evaluated the efficacy of chondrogenesis of the encapsulated hBMSCs, using hBMSCs seeded in agarose as control. The ability of hBMSC-laden mGL constructs to integrate with host tissues after implantation was further investigated utilizing an in vitro cartilage repair model. The results showed that the mGL hydrogel, which could be photopolymerized in air and aqueous solution, supports hBMSC growth and TGF-β3-induced chondrogenesis. Compared with agarose, mGL constructs laden with hBMSCs are mechanically stronger with time, and integrate well with native cartilage tissue upon implantation based on push-out mechanical testing. VL-photocrosslinked mGL scaffold thus represents a promising scaffold for cell-based repair and resurfacing of articular cartilage defects.
封装在具有软骨生成支持作用的三维水凝胶支架中的软骨祖细胞,是一种用于关节软骨修复的、有前景的再生方法。在本研究中,我们开发了一种可注射、可生物降解的基于甲基丙烯酸化明胶(mGL)的水凝胶,它能够通过在空气或水溶液中可见光(VL)激活的交联实现快速凝胶化。温和的光交联条件允许在凝胶化过程中加入细胞。封装的人骨髓间充质干细胞(hBMSC)在整个支架中显示出高的长期存活率(长达90天)。为了评估mGL水凝胶在软骨组织工程中的适用性,我们以接种在琼脂糖中的hBMSC作为对照,评估了封装的hBMSC软骨生成的功效。利用体外软骨修复模型,进一步研究了负载hBMSC的mGL构建体植入后与宿主组织整合的能力。结果表明,可在空气和水溶液中光聚合的mGL水凝胶支持hBMSC生长和TGF-β3诱导的软骨生成。与琼脂糖相比,负载hBMSC的mGL构建体随着时间推移机械强度更高,并且基于推出式力学测试,植入后能与天然软骨组织良好整合。因此,VL光交联的mGL支架是一种用于基于细胞的关节软骨缺损修复和表面重建的有前景的支架。