Radiation-Induced Fibrosis Effects on Incisional Wound Healing: Investigating Tissue Remodeling Changes with a Tension Model
Danae Kawamoto-Duran, BA; Jaden Tarter; Michael T. Longaker, MD, MBA; Derrick C. Wan, MD
Introduction: Despite advancements in radiation therapy, radiation-induced fibrosis (RIF) remains a major challenge, leading to excessive scarring, impaired wound healing, and extracellular matrix (ECM) remodeling. This study examines differences in incisional wound healing between irradiated and non-irradiated skin, utilizing an exogenous mechanical loading model to mimic human hypertrophic scarring.
Methods: Forty-five adult female C57BL/6J mice were divided into four groups: (1) non-irradiated without tension, (2) non-irradiated with tension, (3) irradiated without tension, and (4) irradiated with tension. Mice in irradiated groups received 30 Gy of fractionated dorsal radiation to induce chronic fibrosis. A standardized 2 cm incisional wound was created, and mechanical tension was applied using a distraction device post-incision. The device was incrementally adjusted to progressively widen the wound by 2 mm over six cycles. Tissue samples were harvested at 1, 3, and 10 weeks post-wounding for histological analysis.
Results: Histological examination revealed significant differences between irradiated and non-irradiated incisional wounds, including ECM thickening and changes in collagen density. H&E staining demonstrated an increase in scar width in wounds subjected to mechanical tension compared to non-tension wounds. Masson’s Trichrome staining showed increased ECM deposition and collagen density, and structural disorganization in irradiated wounds compared to non-irradiated controls. Comparative analysis of irradiated wounds under tension versus non-tension conditions revealed distinct ECM remodeling patterns, characterized by greater collagen deposition.
Conclusion: These findings highlight the impact of radiation on incisional wound healing and fibrosis progression, using a tension model to replicate human scarring. Understanding these mechanisms may provide insights to improve post-radiation wound healing.