Delayed collagen production without myofibroblast formation contributes to reduced scarring in adult skin micro-wounds

In adult mammals, wound healing predominantly follows a fibrotic pathway, culminating in scar formation. However, cutaneous micro-wounds generated via fractional photothermolysis, a modality that produces a constellation of microthermal zones (MTZs), exhibit a markedly different healing trajectory. Our study delineates the cellular attributes of these MTZs, underscoring a temporally limited, subclinical inflammatory milieu concomitant with rapid re-epithelialization within 24 hours. This wound closure is facilitated by the activation of genes associated with keratinocyte migration and differentiation. In contrast to macrothermal wounds, which predominantly heal through a robust myofibroblast-mediated collagen deposition, MTZs are characterized by absence of wound contraction and feature delayed collagen remodeling, initiating 5-6 weeks post-injury. This distinct wound-healing is characterized by a rapid re-epithelialization process and a muted inflammatory response, which collectively serve to mitigate excessive myofibroblast activation. Furthermore, we identify an initial reparative phase characterized by a heterogeneous extracellular matrix protein composition, which precedes the delayed collagen remodeling. These findings extend our understanding of cutaneous wound healing and may have significant implications for the optimization of therapeutic strategies aimed at mitigating scar formation.