双缓释载药壳聚糖/羟基磷灰石复合材料在牙周组织工程中的研究

Periodontal defects can be repaired by periodontal scaffolds in clinical application. Currently used scaffolds have been blamed of many weakness in restoring periodontal defects, such as easy-absorption and GvHD. Chitosan (C) is a biological macromolecule polymer, with biocompatibility and healing tissue, and has been applied in tissue regeneration. However, its application is bothered by relatively lower compressive strength and faster biodegradation. Hydroxyapatite (HA) is bestowed with better bioactivity to promote cell adherence, proliferation and differentiation. C/HA composites is thought to have better bioactivity and physicochemical properties. Chitosan-coating RGD/HA composites loading bone morphogenetic protein (BMP-7) and platelet derived growth factor (PDGF) could be conducted the chemotaxis of periodontal ligament stem cells to preferably promote the osteogenesis and angiogenesis for periodontal repair. This study aims at preparing the RGD coated C/HA composites loading BMP-7 and PDGF, as well as investigating in vivo periodontal defect treating research to shed light on the detail mechanism of MSC differentiation and tissue regeneration. We believe that this project will certainly further consolidate the osteogenesis and angiogenesis in periodontal repair process and make great sense in providing new strategies for clinical application.

目前临床上主要用支架材料修复牙周缺损，但易出现支架吸收过快、免疫排斥等不良反应。壳聚糖（C）具有生物相容性好、促进组织愈合等特性，但其抗压强度较弱且降解过快。而羟基磷灰石（HA）具有良好的生物学活性，能够促进细胞粘附、增殖和分化，将其与C结合后的复合支架（C/HA）有望拥有更优异的理化及生物学特性，弥补C自身缺陷。同时将BMP-7和PDGF负载C/HA复合材料，通过精氨酸-甘氨酸-天冬氨酸（RGD）修饰双载药的C/HA趋化牙周膜干细胞（PDLSCs），双重促进PDLSCs成骨、成血管作用，强化牙周缺损修复。本课题旨在构建RGD修饰的双因子C/HA生物材料，在评价复合生物材料修复牙周组织缺损的基础上，探寻其在牙周膜干细胞增殖分化中的作用和机制，为进一步探讨牙周膜干细胞成骨、成血管向分化奠定理论基础，为牙周和口腔组织再生修复研究和临床转化提供新的思路。

目前临床上主要用支架材料修复牙周缺损，但易出现支架吸收过快、免疫排斥等不良反应。壳聚糖（C）具有生物相容性好、促进组织愈合等特性，但其抗压强度较弱且降解过快。而羟基磷灰石（HA）具有良好的生物学活性，并且具有一定的理化性能，将其与C结合后的复合支架（C/HA）有望拥有更优异的理化及生物学特性，弥补C自身缺陷。同时将BMP-7和PDGF负载C/HA复合材料，通过精氨酸-甘氨酸-天冬氨酸（RGD）修饰双载药的C/HA趋化牙周膜干细胞（PDLSCs），协同促进PDLSCs成骨、成血管作用。并用奥硝唑（ORN）药物抗炎，强化牙周缺损修复。本课题通过构建RGD修饰的双因子药物C/HA生物材料，并进一步评价复合材料体外对PDLSCs生物性能影响及体内修复牙周组织缺损能力，结果显示该复合材料在体内外具有良好的促牙周修复能力。本研究旨在评价复合生物材料修复牙周组织缺损的基础上，在探寻其在牙周膜干细胞增殖分化中的作用和机制，为进一步探讨牙周膜干细胞成骨、成血管向分化奠定理论基础，为牙周和口腔组织再生修复研究和临床转化提供新的思路。