建立干细胞载体材料复合体三维重建皮肤动物模型

皮肤是人体最大的器官，重大皮肤损伤严重危害人类健康，但目前缺乏有效治疗方法。支架材料复合干细胞实现原位再生皮肤类器官产品是重大皮肤损伤理想的治疗手段，而现有产品存在干细胞存活率低、临床疗效欠佳等问题。本项目研究目标：通过三维重建功能性皮肤技术，实现重大损伤皮肤组织的结构性再生和功能性修复。项目开展了支架材料复合干细胞促进大鼠皮肤缺损创面愈合的实验研究，建立了大动物全层创面缺损模型，探索了无瘢痕愈合机制，进行了皮肤创面高质量愈合研究，实施了汗腺、毛发等附属器再生相关研究。通过课题的实施，我们获得一系列成果：（1）1种干细胞友好性生物载体材料；（2）基于干细胞结合生物载体材料的原位皮肤再生技术，构建重大皮肤缺损无疤痕高效愈合体系，成功再生毛发、汗腺等附属器官，实现皮肤结构性修复与功能性再生;（3）基于生物载体材料-外泌体复合体实现皮肤损伤高效愈合，形成皮肤创面无细胞替代治疗新方案；（4）国际上首次构建了小鼠汗腺的单细胞RNA+ATAC组学数据库，绘制了皮肤汗腺发育图谱，发现汗腺发育调控关键转录因子，构建高分化汗腺类器官并成功移植体内实现汗腺原位再生；（5）实现超声调控组织干细胞的创面高效愈合；（6）提出超声促进毛发再生新理论；

The skin is the largest organ of the human body. Severe skin injuries severely endanger human health, yet effective treatment options remain scarce at present. Combining scaffold materials with stem cells to produce in situ regenerative skin organoid products is an ideal therapeutic approach for severe skin defects, but existing products suffer from issues such as low survival rate of stem cells and unsatisfactory clinical efficacy. The research objective of this project is to achieve structural regeneration and functional repair of severely injured skin tissues through three-dimensional functional skin reconstruction technology. The project carried out experimental studies on scaffold materials combined with stem cells to promote wound healing in rat skin defects, established large animal full-thickness wound defect models, explored the scar-free healing mechanism, conducted studies on high-quality healing of skin wounds, and implemented research related to the regeneration of skin appendages such as sweat glands and hair follicles. Through the implementation of this project, a series of achievements have been obtained: (1) One stem cell-friendly biocarrier material; (2) Based on the in situ skin regeneration technology combining stem cells and biocarrier materials, an efficient scar-free healing system for severe skin defects has been constructed, hair follicles, sweat glands and other appendages have been successfully regenerated, and structural repair and functional regeneration of skin have been achieved; (3) Efficient healing of skin injuries has been realized using biocarrier material-exosome complexes, forming a novel cell-free alternative therapeutic regimen for skin wounds; (4) For the first time globally, a single-cell RNA+ATAC omics database of mouse sweat glands has been constructed, the developmental atlas of skin sweat glands has been mapped, key transcription factors regulating sweat gland development have been identified, highly differentiated sweat gland organoids have been constructed and successfully transplanted in vivo to achieve in situ regeneration of sweat glands; (5) Efficient wound healing of tissue stem cells regulated by ultrasound has been realized; (6) A novel theory of ultrasound promoting hair regeneration has been proposed.