This work presents a research project dedicated to establishing a new in vivo, in human cutaneous wound healing model using a unique combination of laser induced microscopic wounds and latest generation non-invasive optical imaging creating objective data points. It was conducted mainly at the Universities Hospitals of Geneva in collaboration with the Core Facilities of the University of Geneva and the University Hospital in Lausanne. To validate this wound healing model, we choose to investigate the therapeutic efficacy of silicone gels as previously approved device for wound healing.

Lasers used according to the principles of FP can generate highly reproducible microscopic wounds (MTZs) in the human skin. A laser induced MTZs were created in human skin and evaluated with standardized imaging‑based methodologies characterizing epidermal repair and inflammatory response. With this aim, we developed a portable device (Dermobile) for quantitative erythema evaluation and hence indirect inflammation measurement. It was found a sufficient tool for quantitative erythema indices evaluation compared to a commercially available platform commonly considered as gold standard for erythema evaluation in the clinical setting. Another methodological benchmark was to compare in between reflectance confocal microscopy (RCM) and line‑field confocal optical coherence (LC‑OCT) as best tool for multimodal assessment of epidermal wound‑healing. The LC‑OCT device provides non-invasive direct visualization of the architecture and structure of laser‑induced MTZs on a microscopic scale and enables fast and reliable quantification of their depth, width, and volume. Since the 3D acquisition is almost free of movement artifacts it appears to be superior to image acquisition with confocal microscopy in this indication. Additionally, we were able to use artificial‑intelligence processing of the acquired LC-OCT images to complete volumetric nuclear segmentation. This allowed for the first time an automatic computation of LC-OCT based metrics in the wound healing setting. The findings from this methodological research track were then used in an in-vivo, in-human randomized, prospective clinical trial (BASEC 2022‑D0083m ClinicalTrials.gov (NCT05614557) to monitor the impact of two silicone based on laser induced skin wounds (MTZs) in healthy adult volunteer forearms. In this trial it was found that the application of silicone formulations reduced acute erythema and accelerated significantly re‑epithelialization (p << 0,0001) compared to untreated areas. The innovative and costume-developed methodology for acute wound creation and wound healing evaluation was able to provide reliable, objective, non-invasive endpoint metrics. This work establishes a new framework for human wound‑healing research, uniting clinical laser dermatology and latest generation imaging modalities and AI‑assisted analysis. It furthermore demonstrates that LC‑OCT can serve as reliable surrogates for histology, offering fast and reliable assessments of therapeutic interventions aimed to improve human wound healing.