Different Retinoid Micellar Formulations on Wound Healing: Efficacy and Collagen Structure

Background: The formation of wounds or scars often compromises skin anatomy and function, necessitating effective management to restore tissue integrity. Current interventions, including wound debridement, hyperbaric oxygen therapy, antibiotics, wound dressings, and surgical procedures, can be effective but are sometimes limited by high costs and the increasing prevalence of drug resistance. These challenges highlight the need for innovative, cost-effective, and therapeutic alternatives. Method. Our earlier studies assessed the wound closure of wounded human-equivalent epidermal full-thickness skin model (HEFT-SM) with a limited number of Phytoceutical^® retinol micellar formulations for a six-day treatment and found that the retinol micellar formulation accelerated wound closure significantly. In this work, three different types of Phytoceutical^® retinoid formulations, namely 0.3% retinol, 0.3% retinaldehyde, and 0.03% retinoic acid on the early-stage wound healing efficacy and its collagen structure were studied. Haematoxylin and eosin (H&E) staining analysis was used to assess the wound repair of the 3 mm punch wound after two days and the wound healing efficacy defined as the wound diameter contraction in percentage was assessed. The collagen matrix was examined through the use of Masson's trichrome staining and confocal laser scanning microscopy (CLSM) for both qualitative and spatial assessment. Results. All formulations promoted wound contraction, with efficacy ranging from 15 ± 1% to 35 ± 2% after two days. The 0.3% retinol micelles showed the highest activity (35 ± 2%), followed by retinaldehyde (32 ± 3%) and retinoic acid (15 ± 1%). In addition, all treatments appeared to stimulate collagen architectural changes suggestive of remodelling activity. Conclusions. The enhanced wound healing observed may be attributed to increased cellular proliferation and migration within the wound microenvironment, supporting epidermal differentiation and tissue stratification. Furthermore, this work showed that combination of Masson's trichrome staining and confocal laser scanning microscopy (CLSM) is a novel approach for qualitative and spatial assessment of collagen structure.