基于钠米氧化锆/羟基磷灰石复合支架的RU486嵌合反式激活表达系统在颌骨修复中作用的基础研究

Mandibular defects increasing in clinical practices mainly due to tumors, trauma and infection will lead to different drgrees of facial deformity and chewing dysfunction. The usual method for mandibular defect repair is to connect both ends of the bone defect with bone repair materials playing a supporting role, but poor blood supply, infection, rejection and shift were accompanied usually. In this study, nanometer zirconia/hydroxypatite composite material is chosen to mandibular defcts repair tissue engineering scaffold for its better biological activity and high strength, combined with the in vitro gene therapy and tissue engineering thechnology, so we try to observe effects on mandibular defects repair which is regulated through gene transfected bone tissue engineering. VEGF and LMP-1 genes were subcloned into the inducible expression vector and transfected to bone marrow mesenchymal stem cells(BMSCs), so that the target proteins were expressed; the tissue engineering of bone combined with the gene transfection processing is to replanted to the animal models for repairing mandibular defect. The enhanced BMSCs early celladhesion, vascularization and osteogenic aility can increase the amount of bone formation in vio and accerlerate the process of bone defectsrepaire and bone healing. This study attempts to regulate cell adhesion, angiongenesis osteogenesis levels on BMSCs with three different genes which not only perfomr their bilogical function respectively, but also exert a synergistic effects. When inducer Dexamethasone is added to inducible expression system in aim to precise regulation of target gene experssion, which can induce osteogenesis promotion by itself, the double BMSCs osteogenic induction is achieved. This method is expected to become an effective and feasible bone tissue engineering strategies, also provide a new idea for other tissue engineering research.

颌骨缺损原因主要有肿瘤、外伤、感染等，常导致面部畸形和咀嚼功能障碍。目前常用的修复方法常发生移植骨吸收、供血不良，且多有感染、排异并发。本研究选择纳米氧化锆/羟基磷灰石复合材料为支架，利用其较好的生物活性和较高的强度，将VEGF和LMP-1基因通过可诱导表达载体导入骨髓间质干细胞(BMSCs)，以获得共表达，将经基因转染处理所获得的组织工程化骨回植动物体内修复下颌骨缺损。本研究试图通过VEGF和LMP-1对BMSCs血管生成，成骨作用不同功能层次分别进行调控，不但执行各自的生物学功能，且存在协同效应，加入诱导剂通过诱导表达系统精确调控目标基因的表达，从而实现对BMSCs成骨的双重诱导，本项目联合应用基因治疗和组织工程技术，有望成为一种有效可行的骨组织工程策略，也为其他相关的组织组织工程研究提供一个新思路。

颌骨缺损原因主要有肿瘤、外伤、感染等，常导致面部畸形和咀嚼功能障碍。目前常用的修复方法常发生移植骨吸收、供血不良，且多有感染、排异并发。本研究选择纳米氧化锆/羟基磷灰石复合材料为支架，利用其较好的生物活性和较高的强度，将VEGF和LMP-1基因通过可诱导表达载体导入骨髓间质干细胞(BMSCs)，以获得共表达，将经基因转染处理所获得的组织工程化骨回植动物体内修复下颌骨缺损。本研究试图通过VEGF和LMP-1对BMSCs血管生成，成骨作用不同功能层次分别进行调控，不但执行各自的生物学功能，且存在协同效应，加入诱导剂通过诱导表达系统精确调控目标基因的表达，从而实现对BMSCs成骨的双重诱导，本项目联合应用基因治疗和组织工程技术，有望成为一种有效可行的骨组织工程策略，也为其他相关的组织工程研究提供一个新思路。