TP508多肽修饰的高分子涂层镁合金修复眼眶骨缺损的作用及其机制研究

眼眶外伤、肿瘤等易引起眼眶骨缺损，导致视功能障碍和颅面畸形，需要应用材料修复。但由于眶壁菲薄、局部血供差、骨再生能力低，故修复效果差。现有修复材料不可降解，存在感染、排异等风险。因此，研发适应眼眶骨缺损特点的修复材料是研究重点。项目组前期研发了一种新型可降解镁合金JDBM，具有机械性能适宜、生物相容性好等特点，有望成为眼眶骨缺损修复的理想材料，但其降解速率过快，无法与眼眶新骨形成速度匹配，制约了应用前景。本项目拟采用表面改性技术在JDBM表面构筑功能化生物活性材料PFM，通过改变PFM厚度调控镁合金降解速率；进而将PFM作为桥接媒介，高效连接促血管生成因子TP508多肽，构建新型JDBM-PFM-TP508材料，评价其修复眼眶骨缺损的安全性和有效性。同时，通过阐明TP508-SH2D2A-VEGF-血管形成和骨基质矿化调控网络，揭示该材料促成骨作用机制，为其临床应用提供实验基础和理论依据。

Orbital bone defect, usually caused by orbital trauma or tumor, will result in visual dysfunction and craniofacial deformity, which requires materials to repair. However, the repair efficacy is poor due to the thin orbital wall, poor local blood supply, and low osteogenesis efficiency. Moreover, non-degradable materials are presently applied in the clinical practice, but their long-term existence inside the body will increase such risks as infection and rejection. Therefore, the development of materials that adapt to the characteristics of orbital bone repair is the key point. In the previous study, authors developed a novel degradable magnesium alloy-JDBM. It showed great mechanical properties, biocompatibility and osteogenic capability, which made it an ideal material for orbital bone defect repair. However, its degradation rate didn’t match with the rate of new bone formation in the orbit, which greatly restricted its application in orbital bone defect repair. This project aims to control the degradation rate by coating a functional material PFM on the surface of JDBM and adjusting the thickness of PFM. Then, authors plan to develop a novel magnesium material JDBM-PFM-TP508 by combining an angiogenic peptide, TP508, to PFM, and to evaluate its biocompatibility and efficacy in orbital bone defect repair. Moreover, this project intends to explore the osteogenic mechanisms of this material by identification of TP508-SH2D2A-VEGF-angiogenesis-osteogenesis regulatory network. This project will shed light on the clinical application of novel degradable magnesium alloys by provision with theoretical basis.