碳硅橡胶表面微拓扑结构通过ECM调控TGF-β/Smad信号通路抑制成纤维细胞成肌转化的机制

The long term implantation of silicone rubber (SR) formed capsule and its contracture are the main factors leading to the failure of tissue defect repair in plastic surgery, however, the molecular mechanism is far from clear. Previous studies have found that the transformation ability of the fibroblasts to myofibroblasts is weakened on the surface of the carbon ion implanted SR and have thinner capsule thickness. Further characterization of material shown that the hydrophobicity, surface potential and surface nanotopology change. Based on the literature report and previous work, we put forward the hypothesis that the extracellular matrix ECM is controlled by surface nanotopology of the carbon ion implanted silicone rubber, further regulates the TGF- 1 beta complex and TGF- beta /Smad signaling pathway on the transformation of fibroblasts into myofibroblasts. In this study, we used ion implantation and atomic force microscopy (AFM) to fabricate the micro structure model, combined with in vitro cell experiment and in vivo implantation, study material surface nanotopology on the effect of fibroblasts transformed by RNAi, qPCR, gelatin zymography, immunohistochemistry and WB techniques, and explore the mechanism of intracellular and extracellular signal regulation. This study is expected to provide a new basis for the molecular mechanism of the capsule and its regulation, and provide a theoretical basis for the research and development of new materials with biological functions.

硅橡胶长时间植入体内诱发的包膜及其挛缩问题一直是导致整形外科中组织缺损修复术失败的首要因素且其分子机制还远未阐明。课题组前期研究发现，碳离子注入硅橡胶表面成纤维细胞向肌成纤维细胞转化能力减弱，包膜厚度较薄，进一步对碳硅橡胶材料表征显示，亲疏水性、表面电位以及表面微拓扑结构发生变化。然而，TGF-β是目前已知且明确的调控成肌转化的分子。结合文献报道及前期工作基础，我们提出：“碳硅橡胶表面微拓扑结构通过影响胞外基质ECM，调控TGF-β静息复合物，影响TGF-β/Smad信号通路，抑制成纤维细胞成肌转化”的假设。为了验证上述假设，本研究拟采用离子注入及AFM纳米刻蚀等技术构建微拓扑结构材料模型，结合体外实验及动物体内植入实验探讨材料表面微拓扑结构对成纤维细胞转化的影响，并探究其胞内外信号调节机制。该研究有望为包膜及其挛缩调控的分子机制作出新的探讨，同时也为具有生物功能的新材料研发提供理论依据。

硅橡胶长时间植入体内诱发的包膜及其挛缩问题一直是导致整形外科中组织缺损修复术失败的首要因素且其分子机制还远未阐明。课题组前期研究发现，碳离子注入硅橡胶表面成纤维细胞向肌成纤维细胞转化能力减弱，包膜厚度较薄，进一步对碳硅橡胶材料表征显示，亲疏水性、表面电位以及表面微拓扑结构发生变化。然而，TGF-β是目前已知且明确的调控成肌转化的分子。结合文献报道及前期工作基础，我们提出:“碳硅橡胶表面微拓扑结构通过影响胞外基质ECM，调控TGF-β静息复合物，影响TGF-β/Smad信号通路，抑制成纤维细胞成肌转化”的假设。为了验证上述假设，本研究采用了离子注入等技术构建微拓扑结构材料模型，结合体外实验及动物体内植入实验探讨材料表面微拓扑结构对成纤维细胞转化的影响，并探究其胞内外信号调节机制。研究结果发现，具有微拓扑结构的硅橡胶材料可以明显抑制人成纤维细胞的成肌转化，该微拓扑结构通过细胞胞外基质等相关蛋白调控TGF-β/Smad信号通路，影响人成纤维细胞的成肌转化。进一步的体内及体外实验也证实了该假说。此外，采用双离子注入技术构建的碳银硅橡胶材料具有较好的生物安全性，并具有极佳的抗菌性。体内实验显示出相对普通硅橡胶较薄的包膜形成。该研究成果有望为包膜及其挛缩调控的分子机制作出新的探讨，同时也为具有生物功能的新材料研发提供理论依据。