LAUSR

The hostile oxidative wound microenvironment, defective angiogenesis and uncontrolled release of therapeutic factors are major challenges in improving the diabetic wound healing. Herein, adipose-derived stem cell (ADSC)-derived exosomes (Exos) were firstly loaded into Ag@bovine serum albumin (BSA) nanoflowers (Exos-Ag@BSA NFs) to form a protective "pollen-flower" delivery structure, which were further encapsulated into the injectable collagen (Col) hydrogel (Exos-Ag@BSA NFs/Col) for concurrent remodeling of the oxidative wound microenvironment and precise release of Exos. The Exos-Ag@BSA NFs could selectively dissociate in an oxidative wound microenvironment, which triggered sustained release of Ag ions (Ag+ ) and cascaded controllable release of "pollen-like" Exos at the target site, thus protecting Exos from oxidative denaturation. Such a wound microenvironment-activated release property of Ag+ and Exos effectively eliminated bacteria and promoted the apoptosis of impaired oxidative cells, resulting in improved regenerative microenvironment. Additionally, Exos-Ag@BSA NFs/Col markedly accelerated wound healing and regeneration in vivo in a diabetic murine silicone-splinted excisional wound model by promoting blood perfusion, tissues granulation, collagen deposition, neovascularization, angiogenesis, and re-epithelization. We anticipate that this work will inspire the development of more delicate and disease-specific therapeutic systems for clinical wound management. This article is protected by copyright. All rights reserved.