良好的种植体周角化粘膜质量对于种植体生物封闭及远期效果至关重要。组织工程构建的三维结构粘膜已成为口腔软组织重建热点，四维模式下生物模拟粘膜时序性愈合从而提升移植物成血管、成角化上皮、促种植体生物封闭的研究仍未见报道。本课题组前期研究发现，bFGF-KGF联合使用能协同促进血管化；前期制备的同轴静电纺丝壳-核支架可实现多因子时序性缓释；而课题组围绕诱导性多能干细胞(iPSCs)的相关研究揭示了其用于口腔软组织重建的潜能。基于此，本课题首次以同轴电纺时序性缓释双因子为切入点，拟构建一类基于iPSCs的组织工程角化粘膜，通过生长因子释放动力学、结合血管化角化标志物鉴定等手段评价其体外生物学性能；构建犬种植体周粘膜缺损模型、采用激光散斑成像等技术评价材料促进种植体周软组织扩增的效果；并探究双因子介导下粘膜愈合的分子转导机制。研究结果对进一步完善种植学理论，提高牙种植体成功率具有重要意义。

An adequate band of periimplant keratinized mucosa is crucial for biological seal around implants and the long-term success of implant therapy. Three-dimensional bioengineered soft tissue graft (BSTG) has become a research focus in recent years for oral soft tissue reconstruction. However, a BSTG based on the four-dimensional theory with optimal angiogenesis, re-epithelization, re-keratinization, and sealing effects has not been reported. In the previous studies, we found dual delivery of bFGF and KGF can improve angiogenesis during wound healing and we fabricated coaxial electrospinning materials which proved to be a new strategy to construct scaffolds with spaciotemporal release potential of multiple bioactive factors. Our previous studies focusing on induced pluripotent stem cells(iPSCs) also showed that iPSCs were promising seeding cells in soft tissue engineering. Therefore, in the view of spaciotemporal release of bFGF and KGF for the first time, a new BSTG seeded with iPSCs will be constructed. The biological characteristics of the BSTG will be evaluated in vitro by release kinetics of growth factors, identification of angiogenetic markers and keratinization markers. Animals models without periimplant keratinized mucosa will be established and grafted with the BSTG to evaluate its augmentation efficiency. Laser speckle imaging will be used to quantify its angiogenetic potential. Furthermore, the essential genes and signaling pathways regarding bFGF-KGF-induced angiogenesis, re-epitheliulization, re-keratinization will be studied. The results of this program will complement the present theory of implantation, and will be of significance in improving dental implant success.