二甲双胍缓释tHA/PCL引导组织再生膜的制备及其促牙周组织再生作用机制的研究

Guided tissue regeneration (GTR) is a commonly used treatment method for reconstruction of the damaged periodontal tissue caused by periodontitis. Due to the lack of GTR membrane with excellent bioactivity in clinics, it is difficult to achieve satisfactory results after GTR treatment. Therefore, based on the polydopamine-templated hydroxyapatite (tHA) reinforced polycaprolactone (PCL) composite nanofibers which were developed in our earlier work, our team plan to establish a metformin sustained release coating on the surface of tHA/PCL composite nanofibers by employing layer-by-layer self-assembly technology combining with dopamine chemistry and crosslinking chemistry of genipin. Since the metformin could promote the autophagy of stem cells, we hypothesize that the metformin could enhance the ability of stem cells to resist the oxidative stress injury induced by tHA, reduce the cytotoxicity effect of materials, and further improve the biocompatibility and osteogenic activity of composite nanofibers for enhanced efficiency of periodontal tissue regeneration. Meanwhile, this project will also explore the underlying molecular regulatory mechanism of metformin on nanofibers’ bioactivity, and determine the role of metformin in the promotion of periodontal tissue regeneration during GTR treatment. It is believed that this research could provide a theoretical basis for the future clinical application of tHA/PCL GTR membrane functionalized with metformin sustained release coating, and could also offer an enlightening insight into the designing of new repair materials for periodontal tissue regeneration.

引导组织再生（GTR）术是重建因牙周炎而被破坏牙周组织的常用方法。由于临床缺乏具有高诱导活性的GTR膜，导致GTR术后疗效难以令人满意。针对该问题，项目组在前期研发的GTR膜仿生纳米羟基磷灰石（tHA）/聚己内酯（PCL）复合纳米纤维基础上，首次提出利用聚多巴胺共价接枝，层层自组装和京尼平交联技术的结合，在tHA/PCL纤维表面构建二甲双胍（Met）缓释涂层，以期利用Met对干细胞的自噬调节作用，增强干细胞抵抗tHA介导诱发的活性氧氧化应激损伤的能力，降低材料细胞毒性作用，进一步改善纤维的生物相容性及成骨活性，从而提高纤维引导牙周组织再生的效率。同时，本项目将通过分子生物学的实验技术，分析Met调控材料生物活性的分子作用机制，探讨Met在GTR治疗过程中促进牙周组织修复的可能途径，这将为Met缓释tHA/PCL GTR膜的未来临床应用提供理论依据，也将为研发新型牙周组织修复材料提供新思路。

引导组织再生（GTR）术是重建因牙周炎而被破坏牙周组织的常用方法。由于临床缺乏具有高诱导活性的GTR膜，导致GTR术后疗效难以令人满意。针对该问题，项目组在前期研发的GTR膜仿生纳米羟基磷灰石（tHA）/聚己内酯（PCL）复合纳米纤维基础上，利用聚多巴胺共价接枝，层层自组装和京尼平交联技术的结合，在tHA/PCL纤维表面构建二甲双胍（Met）缓释涂层，利用Met对干细胞的自噬调节作用，增强干细胞抵抗tHA介导诱发的活性氧氧化应激损伤的能力，降低材料细胞毒性作用，进一步改善纤维的生物相容性及成骨活性，从而提高纤维引导牙周组织再生的效率。此外，本项目发现通过多聚赖氨酸和羧甲基壳聚糖构建的缓释涂层同时还可以赋予材料一定的抵抗细菌黏附和增殖的能力。总之，本项目为Met缓释tHA/PCL GTR膜的未来临床应用提供了理论依据，也为研发新型牙周组织修复材料提供了新思路。