Tower-shaped super-adhesive microneedles loaded with vitamin A-containing Bletilla striata vesicles: temporally regulated Inflammation resolution and ECM remodeling for scarless wound healing

Pathological scars, resulting from abnormal collagen metabolism during wound healing, pose clinical challenges due to the high recurrence rates of conventional treatments. Therefore, early-stage modulation of the wound healing process is emerging as a pivotal strategy for preventing and treating pathological scars, necessitating precise coordination of vascular regeneration, inflammation regulation, cell migration, and collagen remodeling. Here, we developed a 3D-printed tower-shaped microneedle system (BSEVs@VA-HP MNs) loaded with vitamin A (VA)-containing Bletilla striata vesicles (BSEVs@VA) for functionally staged effects supported by release kinetics in scarless wound healing. The BSEVs@VA-HP MNs demonstrate exceptional mechanical strength, making them highly effective in penetrating the skin, adhering to tissues, and enzyme-responsive degradation. In rat wound models and rabbit ear scar models, the BSEVs@VA-HP MNs gradually dissolve and release BSEVs, which passively target and are internalized by cells. These BSEVs reprogram macrophages toward an M2 phenotype, mediating anti-inflammatory effects while simultaneously promoting angiogenesis and cell migration. Upon cellular internalization, lysosomes degrade BSEVs, liberating VA, which regulates the type I/III collagen balance during tissue remodeling, thereby suppressing myofibroblast activation and facilitating scarless wound healing. This study integrates natural plant-derived vesicles with 3D-printed bioinspired microneedle technology to establish a synergistic, stage-coordinated therapeutic strategy for scarless wound healing.