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, driven by abnormal collagen metabolism during wound healing, pose clinical challenges due to high recurrence rates of conventional treatments. Therefore, early-stage modulation of the wound healing process has emerged as a pivotal strategy for preventing and treating pathological scars, necessitating precise coordination of vascular regeneration, inflammatory regulation, cell migration, and collagen remodeling. Here, we developed a 3D-printed tower-shaped microneedle system (BSEVs@VA-HP MNs) loaded with Bletilla striata vesicles (BSEVs) containing vitamin A (VA) (BSEVs@VA) for temporal scarless wound healing regulation. The BSEVs@VA-HP MNs demonstrate exceptional mechanical strength, making them highly effective for penetrating the skin, adhering to tissues, and degrading in response to enzymes. In rat wound models and rabbit ear scar models, the BSEVs@VA-HP MNs dissolve gradually and release BSEVs, which are passively targeted and internalized by cells. These BSEVs reprogram macrophages toward an M2 phenotype to exert anti-inflammatory effects, while simultaneously promoting angiogenesis and cell migration. Upon cellular internalization, BSEVs are degraded by lysosomes, liberating VA to regulate the balance of type I/III collagen during tissue remodeling, which in turn suppresses myofibroblast activation and facilitates scarless wound healing. This work integrates natural plant-derived vesicles with 3D-printed bioinspired microneedle technology to establish a synergistic paradigm for temporal anti-scarring therapy.