基于纳米二氧化锆/氧化石墨烯复合HIF-1α/LMP-1双基因转染的牙髓干细胞支架修复颌骨缺损的研究

Jaw defect can be seen in patients suffering from maxillofacial tumor, injury or infection. Currently used tissue engineering scaffolds have been blamed of many weakness in fixing jaw defect, such as easy-absorption, unsufficient blood supply, infection and GvHD. ZrO2, as a new scaffold, enjoys optimal biocompatibility and mechanical properties. However, its application is bothered by relatively lower adherent capacity and vascularization. Graphene oxide is bestowed with brilliant protein adherent capacity to promote cell adherence, proliferation and differentiation. Their composite material is thought to have better bioactivity and mechanical properties. DPSCs transfected with HIF-1α and LMP-1 are more efficient in promoting osteogenesis and vasculargenesis for their synergistic effect. Scaffold composited with these DPSCs will certainly further smooth the osteogenesis and bone repair in treating process. This study aims at employing both tissue-engneering and gene-based therapies to construct ZrO2/GO/stem cell composite as well as conducting in vivo bone defect treating research, in order to shed light on the detail mechanism of MSC differentiation and tissue regeneration. We believe that this project will further consolidate the theory of bone repair and make great sense in providing new strategies for clinical application.

目前常用的组织工程支架在修复颌面部骨缺损过程中，容易出现材料吸收过快以及供血不足、感染和排异等不良反应。二氧化锆（ZrO2）具有良好的生物相容性和机械性能，但其较弱的表面吸附能力和低血管化的缺陷限制了其应用。氧化石墨烯（GO）具有优异的蛋白吸附能力，能够促进细胞粘附、增殖和分化，其与ZrO2结合后的复合支架有望拥有更优异的生物学和机械性能。同时，在ZrO2/GO材料上复合HIF-1α/LMP-1转染的DPSCs，通过诱导表达系统精确调控目标基因的表达，发挥协同作用，实现对DPSCs成骨、成血管的双重促进，更有利于骨组织修复。本研究旨在综合应用组织工程和基因治疗的技术，构建ZrO2/GO与干细胞复合的生物材料，开展骨缺损修复的体内研究，在评价其修复骨组织缺损的基础上，阐明其调控间充质干细胞分化及组织再生的分子机制，进一步巩固骨再生修复的理论基础，并对开发有效可行的临床转化手段具有重要意义。

目前常用的组织工程支架在修复颌面部骨缺损过程中，容易出现材料吸收过快以及供血不足、感染和排异等不良反应。二氧化锆（ZrO2）具有良好的生物相容性和机械性能，但其较弱的表面吸附能力和低血管化的缺陷限制了其应用。氧化石墨烯（GO）具有优异的蛋白吸附能力，能够促进细胞粘附、增殖和分化，其与ZrO2结合后的复合支架有望拥有更优异的生物学和机械性能。同时，在ZrO2/GO材料上复合HIF-1α/LMP-1转染的DPSCs，通过诱导表达系统精确调控目标基因的表达，发挥协同作用，实现对DPSCs成骨、成血管的双重促进，更有利于骨组织修复。本研究旨在综合应用组织工程和基因治疗的技术，构建ZrO2/GO与干细胞复合的生物材料，开展骨缺损修复的体内研究，在评价其修复骨组织缺损的基础上，阐明其调控间充质干细胞分化及组织再生的分子机制，进一步巩固骨再生修复的理论基础，并对开发有效可行的临床转化手段具有重要意义。