新型骨-软骨-肌腱三相书页支架对骨腱连接点损伤后梯度结构再生的作用及相关机制研究

项目名称： 新型骨-软骨-肌腱三相书页支架对骨腱连接点损伤后梯度结构再生的作用及相关机制研究

项目编号： No.81472072

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吕红斌

作者单位： 中南大学

项目金额： 80万元

中文摘要： 骨腱连接点损伤是最常见的运动损伤之一，如何促进其快速而优质愈合一直是运动医学领域的难题。典型的骨腱连接点由肌腱、纤维软骨、钙化的纤维软骨和骨四层组织构成。申请人长期从事骨腱连接点损伤修复的研究，发现其损伤愈合以紊乱的瘢痕组织为主，缺少梯度结构的再生。为了创造骨腱界面梯度结构的再生条件，在前期研究中课题组率先制备了去细胞的骨-软骨-肌腱三相书页支架。本课题拟在此三相支架上分别复合向骨、软骨和肌腱方向分化的骨髓间充质干细胞片以及骨、软骨和肌腱的原代细胞片，构建细胞片与骨-软骨-肌腱三相书页支架的复合体，再将其植入兔髌骨髌腱损伤模型，以引导体内干细胞迁移、分化、种植和长入此复合体，采用组织学、分子生物学、影像学和生物力学方法综合评估其对骨腱界面的愈合效果，探讨此新型骨-软骨-肌腱三相书页支架对骨腱连接点梯度结构的再生作用。同时，利用体外实验研究其相关的分子生物学机制。为治疗骨腱损伤提供新的思路。

中文关键词： 组织工程；细胞片；三相书页支架；骨腱愈合；去细胞

英文摘要： Bone tendon junction injury is one of the most common diseases in sports medicine. However, tendon to bone healing is generally recognized as the most difficult hurdle in tendon or ligament reconstructions. The tendon to bone insertion is physiologically characterized with a unique transitional fibrocartilage zone, with calcified collagen fibers connecting to bone and non-calcified collagen fibers connecting to tendon. The applicant has spent over ten years to explore how to enhance tendon to bone healing with an established partial patellectomy model in rabbits. The previous studies showed that the tendon/bone interface was filled with fibrous scar tissue and lack of regeneration of graded tissue organization. In order to provide the best environment for tendon to bone healing, we developed a novel decellularized bone, fibrocartilage and tendon book scaffold with multilayers. In the current protocol, we will harvest the bone marrow stromal cells (BMSC) and first culture it separately in osteogenic, chondrogenic and tenogenic stimulation media. Osteoblasts, chondrocyte and fibroblasts will also be harvested. These cells will be used to make cell sheets. These cell sheets were implanted into the three-phased multilayered decellularized book scaffold accordingly. This novel scaffolds will be transplanted into the partial patellectomy model, to study the effect of this novel scaffold on tendon to bone healing and the regeneration of graded tendon to bone interface. Furthermore, the related molecular biological mechanism will be explored with in vitro model.

英文关键词： Tissue engineering;Cell sheet;Three-phase book scaffold;Tendon to bone healing;Decellularization