Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
ACS Nano. 2021 Apr 27;15(4):6352-6368. doi: 10.1021/acsnano.0c07714. Epub 2021 Mar 16.
Excessive scar formation has adverse physiological and psychological effects on patients; therefore, a therapeutic strategy for rapid wound healing and reduced scar formation is urgently needed. Herein, bilayered thiolated alginate/PEG diacrylate (BSSPD) hydrogels were fabricated for sequential release of small extracellular vesicles (sEVs), which acted in different wound healing phases, to achieve rapid and scarless wound healing. The sEVs secreted by bone marrow derived mesenchymal stem cells (B-sEVs) were released from the lower layer of the hydrogels to promote angiogenesis and collagen deposition by accelerating fibroblast and endothelial cell proliferation and migration during the early inflammation and proliferation phases, while sEVs secreted by miR-29b-3p-enriched bone marrow derived mesenchymal stem cells were released from the upper layer of the hydrogels and suppressed excessive capillary proliferation and collagen deposition during the late proliferation and maturation phases. In a full-thickness skin defect model of rats and rabbit ears, the wound repair rate, angiogenesis, and collagen deposition were evaluated at different time points after treatment with BSSPD loaded with B-sEVs. Interestingly, during the end of the maturation phase in the model, tissues in the groups treated with BSSPD loaded with sEVs for sequential release (SR-sEVs@BSSPD) exhibited a more uniform vascular structure distribution, more regular collagen arrangement, and lower volume of hyperplastic scar tissue than tissues in the other groups. Hence, SR-sEVs@BSSPD based on skin repair phases was successfully designed and has considerable potential as a cell-free therapy for scarless wound healing.
过度的瘢痕形成会对患者的生理和心理产生不良影响；因此，迫切需要一种能够快速愈合伤口和减少瘢痕形成的治疗策略。在此，我们制备了双层巯基化藻酸盐/聚乙二醇二丙烯酸酯（BSSPD）水凝胶，用于顺序释放小细胞外囊泡（sEVs），这些 sEVs 作用于不同的伤口愈合阶段，以实现快速无瘢痕的伤口愈合。骨髓间充质干细胞（BMSC）分泌的 sEVs 从水凝胶的下层释放出来，通过加速成纤维细胞和内皮细胞的增殖和迁移，在早期炎症和增殖阶段促进血管生成和胶原沉积，而富含 miR-29b-3p 的 BMSC 分泌的 sEVs 则从水凝胶的上层释放出来，并在晚期增殖和成熟阶段抑制过度的毛细血管增殖和胶原沉积。在大鼠全层皮肤缺损模型和兔耳中，在不同时间点用负载 B-sEV 的 BSSPD 处理后，评估了伤口修复率、血管生成和胶原沉积。有趣的是，在模型的成熟阶段末期，用负载 sEVs 的 BSSPD 进行顺序释放（SR-sEVs@BSSPD）治疗的组的组织表现出更均匀的血管结构分布、更规则的胶原排列和更低体积的增生性瘢痕组织，而其他组的组织则没有。因此，基于皮肤修复阶段的 SR-sEVs@BSSPD 被成功设计出来，并具有作为无瘢痕伤口愈合的无细胞治疗的巨大潜力。
