葛根素介导的可注射型钙离子敏感水凝胶用于间充质干细胞移植治疗骨关节炎的研究

Osteoarthritis is a chronic joint disease characterized by arthritis cartilage degeneration, which could not be completely cured by conventional drug therapy or surgery. Mesenchymal stem cells (MSCs) transplantation therapy, a new technology developed recently, brings new hope for the treatment of osteoarthritis. Based on the high concentration of calcium ion in the synovial fluid of osteoarthritis patients, an injectable calcium ion sensitive hydrogel that composed of puerarin and sodium alginate can be acted as carrier for MSCs transplantation and be used for articular cartilage repair. After intra-articular injection of MSCs loaded in the hydrogel, gelation will form rapidly by puerarin and alginate under the mediation of calcium ion in the synovial fluid, and the MSCs will be immobilized on cartilage defects. Puerarin and tetrandrine combined with the theory of compatibility of traditional Chinese medicine (TCM) composition can be controlled release simultaneously. Peurarin, the component of hydrogel, can be sustained-release and induce MSCs chondrogenic differentiation along with slow degradation of hydrogel. Moreover, tetrandrine can maintain the function of chondrocytes and reduce the tissue rejection reaction. In this project, the molecular mechanism of MSCs chondrogenic differentiation induced by the compatibility of puerarin and tetrandrine will be investigated, which will be used to build a smart hydrogel drug delivery system for MSCs transplantation with TCM characteristics and independent intellectual property rights.

骨关节炎是一种以关节软骨退行性病变为特征的慢性关节疾病，常规药物疗法和外科手术都无法完全治愈。近年来兴起的间充质干细胞(MSCs)移植疗法，为骨关节炎的治疗带来新的希望。项目基于骨关节炎患者关节液中钙离子浓度较高的特点，以葛根素和海藻酸钠构建可注射型钙离子敏感水凝胶作为MSCs移植的载体，用于骨关节炎关节软骨的微创修复治疗。将MSCs负载在水凝胶中注入关节腔，在关节液的钙离子作用下，葛根素介导海藻酸钠迅速发生凝胶化，将MSCs固定在软骨缺损部位。依据中药组分配伍理论，将粉防己碱与葛根素配伍使用，由凝胶体系同时控制释放。其中葛根素既是凝胶构成组分，又可随凝胶缓慢降解而释放，诱导MSCs向软骨细胞分化。粉防己碱维持软骨细胞功能，降低组织排异反应。本研究将探索葛根素和粉防己碱组分配伍诱导MSCs成软骨分化的分子机制，构建可用于MSCs移植的具有中医药特色和自主知识产权的智能水凝胶系统。

近年来骨髓间充质干细胞(BMSCs)移植技术的发展，为骨关节炎治疗提供了新的方法。BMSCs的诱导分化和细胞定位，是制约移植的技术难点。本项目基于骨关节炎患者关节液中钙离子浓度较高的特点，以葛根素和海藻酸钠构建可注射型钙离子敏感水凝胶作为BMSCs移植的载体，用于骨关节炎关节软骨的微创修复治疗。筛选了合适的葛根素与粉防己碱配伍比例，诱导BMSCs成软骨分化；制备了具有良好的生物相容性的钙离子敏感葛根素-海藻酸钙水凝胶。将BMSCs负载在水凝胶中注入关节腔，在关节液的钙离子作用下，葛根素介导海藻酸钙凝胶形成，将BMSCs固定在软骨缺损部位。葛根素和粉防己碱配伍不仅可以诱导BMSCs向软骨细胞分化，而且具有抗炎与降低组织排异反应的活性。阐明了葛根素和粉防己碱联合诱导BMSCs向软骨分化的分子机制，构建了可用于BMSCs移植载体的控释葛根素和粉防己碱的水凝胶系统，用于骨关节炎的治疗。