Nedunchezian Swathi, Wu Che-Wei, Wu Shung-Cheng, Chen Chung-Hwan, Chang Je-Ken, Wang Chih-Kuang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80701, Taiwan.
Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 80701, Taiwan.
Polymers (Basel). 2022 May 13;14(10):2003. doi: 10.3390/polym14102003.
Developing a biomaterial suitable for adipose-derived stem cell (ADSCs)-laden scaffolds that can directly bond to cartilage tissue surfaces in tissue engineering has still been a significant challenge. The bioinspired hybrid hydrogel approaches based on hyaluronic acid methacryloyl (HAMA) and gelatin methacryloyl (GelMA) appear to have more promise. Herein, we report the cartilage tissue engineering application of a novel photocured hybrid hydrogel system comprising HAMA, GelMA, and 01.0% (/) acrylate-functionalized nano-silica (AFnSi) crosslinker, in addition to describing the preparation of related HAMA, GelMA, and AFnSi materials and confirming their related chemical evidence. The study also examines the physicochemical characteristics of these hybrid hydrogels, including swelling behavior, morphological conformation, mechanical properties, and biodegradation. To further investigate cell viability and chondrogenic differentiation, the hADSCs were loaded with a two-to-one ratio of the HAMA-GelMA (HG) hybrid hydrogel with 01.0% (/) AFnSi crosslinker to examine the process of optimal chondrogenic development. Results showed that the morphological microstructure, mechanical properties, and longer degradation time of the HG+0.5% (/) AFnSi hydrogel demonstrated the acellular novel matrix was optimal to support hADSCs differentiation. In other words, the in vitro experimental results showed that hADSCs laden in the photocured hybrid hydrogel of HG+0.5% (/) AFnSi not only significantly increased chondrogenic marker gene expressions such as SOX-9, aggrecan, and type II collagen expression compared to the HA and HG groups, but also enhanced the expression of sulfated glycosaminoglycan (sGAG) and type II collagen formation. We have concluded that the photocured hybrid hydrogel of HG+0.5% (/) AFnSi will provide a suitable environment for articular cartilage tissue engineering applications.
开发一种适用于负载脂肪干细胞（ADSCs）的支架的生物材料，使其能够在组织工程中直接与软骨组织表面结合，仍然是一项重大挑战。基于甲基丙烯酰化透明质酸（HAMA）和甲基丙烯酰化明胶（GelMA）的仿生混合水凝胶方法似乎更具前景。在此，我们报告了一种新型光固化混合水凝胶系统在软骨组织工程中的应用，该系统由HAMA、GelMA和01.0%（/）丙烯酸酯功能化纳米二氧化硅（AFnSi）交联剂组成，此外还描述了相关HAMA、GelMA和AFnSi材料的制备并确认了它们的相关化学证据。该研究还考察了这些混合水凝胶的物理化学特性，包括溶胀行为、形态构象、力学性能和生物降解性。为了进一步研究细胞活力和软骨形成分化，将人脂肪干细胞以二比一的比例负载到含有01.0%（/）AFnSi交联剂的HAMA-GelMA（HG）混合水凝胶中，以研究最佳软骨形成发育过程。结果表明，HG+0.5%（/）AFnSi水凝胶的形态微观结构、力学性能和更长的降解时间表明，这种无细胞新型基质最适合支持人脂肪干细胞的分化。换句话说，体外实验结果表明，与HA和HG组相比，负载在HG+0.5%（/）AFnSi光固化混合水凝胶中的人脂肪干细胞不仅显著增加了软骨形成标记基因如SOX-9、聚集蛋白聚糖和II型胶原蛋白的表达，还增强了硫酸化糖胺聚糖（sGAG）的表达和II型胶原蛋白的形成。我们得出结论，HG+0.5%（/）AFnSi光固化混合水凝胶将为关节软骨组织工程应用提供合适的环境。
