(WHS-P25) A NOVEL EX VIVO MODEL OF PERISTOMAL SKIN DAMAGE FOR DEVELOPMENT OF OSTOMY ADHESIVES
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
BACKGROUND. Ostomy surgery is often the only effective treatment for diseases affecting normal digestive or urinary function. The resulting stoma, or opening, in the abdomen is affixed with a waste collection pouch that is secured to the surrounding skin with adhesive tape. Ostomy pouches are Class I medical devices and must not only adhere to the skin and protect it from body waste, but also be amenable to routine removal and re-application for the duration of the treatment. Repeated removal of adhesives and exposure to bodily wastes from the stoma (dejecta) causes peristomal skin damage that can lead to complications and reduced quality of life. METHODS & RESULTS. Our goal is to develop novel adhesive formulations that can a) adhere for extended periods of time; b) be removed with minimal skin trauma; and c) minimize the impact of stoma leakage. Human clinical modeling of peristomal skin irritation is costly and difficult to achieve in healthy volunteers, therefore clinical models are challenging as a high-throughput screening tool for formulation development. Therefore, to achieve our goal we developed an ex vivo model of peristomal skin using de-identified, discarded abdominoplasty tissues to identify strong novel adhesive formulation candidates to move into clinical models. Our current objectives are to understand the effects of repeated tape-stripping with 2 different hydrocolloid adhesive formulations and the damage caused to skin by a mixture of digestive enzymes. Morphological analysis of H&E-stained cross sections of tape-stripped tissue (applied and removed five times) revealed distinct differences in the extent of damage to the stratum corneum, ranging from no damage to complete loss with exposure of the stratum granulosum. Transepidermal water loss (TEWL) readings taken immediately after each stripping event correlated with observed epidermal damage. These TEWL results align with results from prior clinical studies of these adhesives. To understand the skin damage resulting from exposure to digestive enzymes in dejecta, we topically applied a cocktail of trypsin, chymotrypsin, and elastase for 1 h to skin tissue. Enzymatic exposure caused significant decompaction of the stratum corneum and ablation of the stratum granulosum, as determined by H&E staining. Moreover, the enzymes significantly reduced the immunofluorescent expression of epidermal barrier proteins filaggrin and loricrin. CONCLUSIONS. Taken together, these results show significant mechanical and enzymatic epidermal barrier damage and modeling of peristomal conditions. Moving forward, we will combine tape-stripping with enzyme exposure to more closely model the combination of factors affecting the peristomal skin and characterize additional adhesive formulations with improved skin protective capabilities. .