Smart ROS-regulating biomimetic hydrogel promotes scarless diabetic wound healing via macrophage reprogramming

The dynamic management of diabetic wound healing remains a major challenge due to the vastly different therapeutic requirements across healing phases and the impaired drug delivery within the pathological microenvironment. To address this, we develop a core-shell structured microfiber composite hydrogels (Bil), inspired by the three-dimensional steel-concrete composite structures in civil engineering, that enables programmed treatment by dynamically regulating ROS and the immune microenvironment. Initially, Bil generates antibacterial ROS under laser irradiation. As the ROS-responsive shell degrades, stem cell-derived exosomes (Exos) are released to promote regeneration, while the exposed nanofibrous core scavenges ROS and facilitates the inflammation-to-proliferation transition. Furthermore, released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. This platform provides spatiotemporal stage-adaptive therapy, significantly enhancing healing through dynamic ROS modulation, precise immune regulation, and improved Exos delivery, ultimately promoting scarless wound regeneration.