Work

114. Development Of An Ex Vivo Human Skin Perfusion Model For Radiation Induced Fibrosis

Year: 2024

Type: article

Abstract: Purpose: Radiation-induced fibrosis (RIF) is a late side effect of external beam radiation therapy. In the acute phase, it manifests as desquamation, erythema, and pain. Over time, patients may develop soft tissue atrophy, alopecia, and stiffness. Current management strategies, including physical therapy, steroids, and fat grafting, often offer limited efficacy. Animal models for studying RIF face limitations due to anatomical disparities with humans, making data translation challenging. In pursuit of a deeper understanding of radiodermatitis mechanisms, we explored the utility of our ex vivo human skin perfusion model to replicate radiation-induced damage. Methods: We Obtained abdominal pannus from panniculectomy procedures. The flap was cannulated through the superficial inferior epigastric artery and perfused with an enriched cell culture media. Following the initial day of perfusion, we subjected the flap to radiation doses of 20 Gy and 40 Gy. The metabolic and physiological viability of the flap was assessed using a catecholamine-stress test. We obtained punch biopsies on days 3, 6, 12, and 16. Histological sections were prepared and stained with H&E and Mason Trichrome techniques to visualize desquamation and collagen deposition, as well as with TUNEL staining to detect cell damage. Results: Flap viability, as evidenced by increased lipolysis and blood pressure in response to catecholamines, persisted through day 16. H&E staining revealed elevated dermal inflammation, dermo-epidermal separation, and collagen deposition in dermis. Masson’s Trichrome staining confirmed augmented fibrotic deposition in the dermis and peri-vascular regions. Gene expression analysis revealed heightened levels of inflammatory and pro-fibrotic genes in the irradiated zones compared to the control area (P<0.001). Conclusion: This system serves as a valuable tool for replicating fibrotic responses and investigating the underlying mechanisms that trigger skin fibrosis. It also offers a platform for testing potential therapeutic interventions aimed at preventing fibrosis.

Source: Plastic & Reconstructive Surgery Global Open

DOI: 10.1097/01.gox.0001015544.91055.17