<< Back to the abstract archive
Development of an ex vivo Human Skin Perfusion Model for Radiation induced Fibrosis
Hamid Malekzadeh, Jose Antonio Arellano, Yusuf Surucu, Wayne Nerone, Fuat Baris Bengur, Jeffrey Gusenoff, Francesco Egro, Asim Ejaz
Department of Plastic Surgery, University of Pittsburgh Medical Center
2024-01-15
Presenter: Hamid Malekzadeh
Affidavit:
Certified
Director Name: J. Peter Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction:
Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer, resulting in movement restriction, pain, and organ dysfunction. Current management strategies often offer limited efficacy. Animal models for studying radiodermatitis face limitations due to anatomical disparities with humans, making data translation challenging. Here we explored the utility of our ex vivo human skin perfusion model to replicate radiation-induced damage.
Methods:
This tissue 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 40 Gy. The metabolic and physiological viability of the flap was assessed using a catecholamine-stress test. Biopsies were obtained every 3 days and histological sections were 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 responses 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 increased fibrotic deposition in the dermis and peri-vascular regions. Gene expression analysis revealed increased levels of inflammatory and pro-fibrotic genes in 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.
