<p>Inherent intra-individual variability in wound pathophysiology presents significant challenges in establishing appropriate control conditions for clinical studies. As a result, the scientific evidence supporting the clinical efficacy of interventions designed to enhance wound healing remains frequently limited. Here, we assess the effects of silicone-based formulations on wound healing using a non-invasive, in vivo multimodal approach. Fractional photothermolysis-induced skin microlesions will be used as in human wound model. Two approved silicone-based formulations, authorized as medical devices for the management of acute and chronic wounds, were randomly applied to distinct test sites on the proximal volar forearm, which had been ablated in a fractional pattern using a CO₂ laser. A third laser ablated test site was left without silicone gel treatment and served as the control. Erythema severity and lesion microarchitecture were assessed using dermoscopy and three-dimensional line-field confocal optical coherence tomography at predefined time points between Day 1 and Day 14 following laser irradiation. The silicone-based formulations significantly reduced acute erythema and its overall intensity. Treatment with these formulations also resulted in a highly significant reduction in lesion area and depth, in addition to a lower inter-individual variability compared to the untreated control. LC-OCT imaging furthermore showed faster restoration of the epidermal barrier, potentially minimizing the risk of infection and related complications, supporting faster wound healing and skin recovery in this in-vivo wound healing model.</p>