Controlled microtrauma opens a regenerative window for appendage-bearing skin repair

Abstract

Adult skin normally resolves injury through rapid closure and fibrotic matrix deposition, often at the cost of permanent appendage loss. We tested whether spatially controlled microtrauma could instead serve as a regenerative entry point when paired with temporally coordinated molecular cues. We engineered a hierarchical extracellular-matrix-based microneedle patch that combines rapid local availability of verteporfin, an inhibitor of YAP-associated mechanotransduction, with sustained retinoic-acid delivery to support follicle-regenerative signalling. The microneedle interface was evaluated in full-thickness rabbit ear wounds, which are prone to hypertrophic scarring, and in Bama miniature-pig wounds, whose skin architecture more closely resembles human skin. Across both models, staged dual-cue treatment accelerated wound closure, reduced collagen-dense scar formation and promoted the appearance of hair-bearing tissue and histologically identifiable follicular structures. These findings support a trauma-guided regeneration framework in which controlled microinjury is used not only for delivery but also to open a transient repair niche that can be molecularly redirected toward appendage-bearing skin restoration. ImportanceMicroneedles are generally treated as minimally invasive delivery devices. Here, the microinjury itself is incorporated into the therapeutic design. The study provides cross-species proof of concept that a patterned injury interface, combined with staged anti-fibrotic and pro-regenerative signalling, can shift wound repair away from fibrotic closure and toward hair-follicle-containing skin. This concise preprint reports the central concept and the rabbit and porcine evidence supporting it; expanded mechanistic and source datasets will be reported separately.