具有促真皮再生活性的丝素基三维支架的构建及性能研究

Repairing dermal tissue defects is a major challenge in the filed of skin regenerative medicine. A novel approach to overcome this challenge is to take advantage of biodegradable natural biomaterials with proper mcrio- or nano-structure and bioactive components. Our research team has previously found that silk fibroin (SF) scaffolds with good biocompatibility could induce dermis formation. However, the repair bioactivity and mechanism of the scaffolds are still limited, which has motivated us to further improve the micro-environment of the scaffolds.We will employ green and mild approach of cultivation techniques under hot wet and slightly dissolve by enzyme degradation to obtain the silk fibroin based scaffolds with mcrio- or nano-structure and bioactive components by incorporating hyaluronic acid (HA), chondroitin sulfate (CS) and vascular endothelial growth factor (VEGF). To insight the methods of controlling mcrio- or nano-structure and bioactive components of the scaffolds, the influenpreparation conditions on the performance of the scaffolds will be investigated. Also, to evaluate the effects of scaffolds’ morphology and structure on the behavior of human vascular endothelial cells and fibroblast cells, the adhesion, proliferation and protein expression of the cells will be examined. In addition, we will investigate the severe dermal tissue defects repair bioactivity of the scaffolds and how such scaffolds induce skin reconstruction by real time-PCR with an animal model. This study will provide essential theory basis for the development of skin defects tissue regeneration.

真皮重建是皮肤再生医学领域的难题，具有微纳米结构和活性组分的可降解生物材料能够模拟皮肤的微环境，为真皮再生修复提供了新方法。本项目组前期研究发现具有良好生物相容性的丝素三维支架能支持真皮的再生，但支架的修复活性较低且其修复机制尚不明确，需深入研究。本研究借助绿色温和的热湿培育技术和酶微降解技术等，在丝素蛋白支架内引入透明质酸、硫酸软骨素和血管内皮细胞生长因子，改善支架的孔结构、微纳米结构和活性；通过研究制备条件对支架理化性能的影响，找到控制支架微纳结构和性能的方法。通过研究人血管内皮细胞和人成纤维细胞在支架内的粘附、分化、增殖等情况，探讨材料的组成和形貌对细胞行为的影响规律；通过支架原位诱导真皮再生实验，探讨支架所携带的物理、化学和生物学信号对真皮再生的影响，利用Real time-PCR等手段，在基因水平和分子水平上揭示支架促真皮修复活性的机制，为组织工程皮肤的研制提供重要理论依据。

真皮重建是皮肤再生医学领域的难题，具有微纳米结构和活性组分的可降解生物材料能够模拟皮肤的微环境，为真皮再生修复提供了新方法。研究发现具有良好生物相容性的丝素三维支架能支持真皮的再生，本研究借助绿色温和的热湿培育技术和酶微降解技术等，在丝素蛋白支架内引入透明质酸、硫酸软骨素和血管内皮细胞生长因子，改善支架的孔结构、微纳米结构和活性；通过研究制备条件对支架理化性能的影响，找到了控制支架微纳结构和性能的方法。通过研究人血管内皮细胞和人成纤维细胞在支架内的粘附、分化、增殖等情况，探讨了材料的组成和形貌对细胞行为的影响规律；通过支架原位诱导真皮再生实验，探讨了支架所携带的物理、化学和生物学信号对真皮再生的影响，利用Real time-PCR等手段，在基因水平和分子水平上揭示支架促真皮修复活性的机制，为组织工程皮肤的研制提供了重要理论依据。项目资助已发表SCI收录论文9篇，申请国家发明专利7项，参加国际学术会议4次，培养硕士研究生4名。项目投入经费25万元，支出经费11.0797万元，剩余经费13.9203万元，剩余经费计划用于本项目后续研究的开展、3篇论文的出版和专利申请维护费用。