近年来，我国骨关节炎发病人数急剧攀升。人骨髓间充质干细胞(hMSCs)由于其各项优点，已成为广泛关注的修复关节软骨的细胞源。然而在初始软骨分化后，hMSCs继续朝向肥大软骨细胞显型分化，导致新生软骨广泛矿化。此问题已成为hMSCs应用于临床软骨修复的主要障碍。糖胺聚糖(GAG)是软骨细胞外基质(ECM)的关键组成部分。硫酸化糖胺多糖已被证明能够吸附并保持各类生长因子的活性。前期实验证明这其中包括多种有利于干细胞软骨分化并能抑制其软骨肥大分化的生长因子。同时硫酸糖胺聚糖所带负电荷能够吸附包括钙离子等正电荷离子，从而改变组织环境中钙离子浓度并影响软骨矿化的过程。本项目提议通过在仿生水凝胶支架材料中加入硫酸根基团以模拟软骨细胞微环境的生物化学特性，并探究其对所封装hMSCs软骨分化及其随后的肥大性软骨组织矿化的调节作用。项目成果不仅有助于开发干细胞软骨修复新疗法，并且也将有助于研发新型支架材料。

The World Health Organization predicts that the number osteoarthritis patients in China will reach 150 million in 2015. Human mesenchymal stem cells (hMSCs) have emerged as a clinically relevant cell source for cartilage repair, due to their multipotency and easy availability. However, after firstly differentiating (chondrogenesis) into chondrocytes (cartilage cells) like cells, hMSCs continue to differentiate toward a hypertrophic phenotype, resulting in extensive mineralization of the neocartilage formed, which should be free of mineralization. This problem, which motivates this proposed work, is now being recognized as a major obstacle to the widespread adoption of hMSCs as a clinically viable cell source for cartilage repair. Glycosaminoglycan (GAG) is a key component of the cartilage extracellular matrix (ECM). Sulfated glycosaminoglycans have been shown to maintain the activity of growth factors,many of which have been shown to promote chondrogenesis and inhibit hypertrophy of hMSCs. Sulfated glycosaminoglycans also attract cations including calcium ions with their negative charges, thereby changing the calcium concentration in the intercellular tissue environment and influencing tissue mineralization. The project proposed to chemically incorporate the sulfate groups in biomaterial hydrogel scaffold to emulate the biochemical properties of the native cartilage cellular microenvironment. This will allow us to investigate the role of sulfation in regulating hMSC chondrogenesis and subsequent hypertrophic tissue mineralization.The results of the project will not only help the development of new stem cell therapies for cartilage repair, but will also guide the design of novel scaffold materials for repairing defects in interfacial regions including ligament/tendon to bone insertions and cartilage to bone interfaces.