Kim Hwan D, Heo Jiseung, Hwang Yongsung, Kwak Seon-Yeong, Park Ok Kyu, Kim Hyunbum, Varghese Shyni, Hwang Nathaniel S
1 School of Chemical and Biological Engineering, BioMAX Institute, Seoul National University , Seoul, Republic of Korea.
Tissue Eng Part A. 2015 Feb;21(3-4):757-66. doi: 10.1089/ten.TEA.2014.0233. Epub 2014 Nov 14.
Articular cartilage damage is a persistent and increasing problem with the aging population. Strategies to achieve complete repair or functional restoration remain a challenge. Photopolymerizing-based hydrogels have long received an attention in the cartilage tissue engineering, due to their unique bioactivities, flexible method of synthesis, range of constituents, and desirable physical characteristics. In the present study, we have introduced unique bioactivity within the photopolymerizing-based hydrogels by copolymerizing polyethylene glycol (PEG) macromers with methacrylated extracellular matrix (ECM) molecules (hyaluronic acid and chondroitin sulfate [CS]) and integrin binding peptides (RGD peptide). Results indicate that cellular morphology, as observed by the actin cytoskeleton structures, was strongly dependent on the type of ECM component as well as the presence of integrin binding moieties. Further, CS-based hydrogel with integrin binding RGD moieties increased the lubricin (or known as superficial zone protein [SZP]) gene expression of the encapsulated chondrocytes. Additionally, CS-based hydrogel displayed cell-responsive degradation and resulted in increased DNA, GAG, and collagen accumulation compared with other hydrogels. This study demonstrates that integrin-mediated interactions within CS microenvironment provide an optimal hydrogel scaffold for cartilage tissue engineering application.
关节软骨损伤是老龄化人口中一个持续且日益严重的问题。实现完全修复或功能恢复的策略仍然是一项挑战。基于光聚合的水凝胶因其独特的生物活性、灵活的合成方法、多样的成分和理想的物理特性,长期以来在软骨组织工程中受到关注。在本研究中,我们通过将聚乙二醇(PEG)大分子单体与甲基丙烯酸化的细胞外基质(ECM)分子(透明质酸和硫酸软骨素[CS])以及整合素结合肽(RGD肽)共聚,在基于光聚合的水凝胶中引入了独特的生物活性。结果表明,通过肌动蛋白细胞骨架结构观察到的细胞形态强烈依赖于ECM成分的类型以及整合素结合部分的存在。此外,含有整合素结合RGD部分的基于CS的水凝胶增加了包封软骨细胞的润滑素(或称为表面区蛋白[SZP])基因表达。另外,基于CS的水凝胶表现出细胞响应性降解,与其他水凝胶相比,导致DNA、糖胺聚糖和胶原蛋白积累增加。本研究表明,CS微环境中整合素介导的相互作用为软骨组织工程应用提供了一种最佳的水凝胶支架。