Optical Coherence Tomography for Assessment of Epithelialization in a Human Ex Vivo Wound Model

ABSTRACT

The ex vivo human skin wound model is a widely accepted model to study wound epithelialization. Due to a lack of animal models that fully replicate human conditions, the ex vivo model is a valuable tool to study mechanisms of wound re-epithelialization, as well as for pre-clinical testing of novel therapeutics. The current standard for assessment of wound healing in this model is histomorphometric analysis, which is labor intensive, time consuming, and requires multiple biological and technical replicates in addition to assessment of different time points. Optical Coherence Tomography (OCT) is an emerging non-invasive imaging technology originally developed for non-invasive retinal scans that avoids the deleterious effects of tissue processing. This study investigated OCT as a novel method for assessing re-epithelialization in the human ex vivo wound model. Excisional ex vivo wounds were created, maintained at air-liquid interface, and healing progression was assessed at days 4 and 7 with OCT and histology. OCT provided adequate resolution to identify the epidermis, the papillary and reticular dermis, and importantly, migrating epithelium in the wound bed. We have deployed OCT as a non-invasive tool to produce, longitudinal "optical biopsies" of ex vivo human wound healing process, and we established an optimal quantification method of re-epithelialization based on en face OCT images of the total wound area. Pairwise statistical analysis of OCT and histology based quantifications for the rate of epithelialization have shown the feasibility and superiority of OCT technology for non-invasive monitoring of human wound epithelialization. Furthermore, we have utilized OCT to evaluate therapeutic potential of allogeneic adipose stem cells revealing their ability to promote re-epithelialization in human ex vivo wounds. OCT technology is promising for its applications in wound healing and evaluation of novel therapeutics in both the laboratory and the clinical settings. This article is protected by copyright. All rights reserved.