Enhancing Wound Healing After Radiation-Induced Fibrosis: Effects of Decellularized Adipose Matrices and Fat Grafting

Introduction: Radiation-induced fibrosis (RIF) is a severe late complication of radiation therapy characterized by chronic ulceration, skin retraction, and impaired wound healing. Despite its prevalence and significant clinical impact, no effective therapies are currently available. Autologous fat grafting has emerged as a common strategy for partially treating irradiated tissue, but its application is limited by donor site availability. A promising alternative is the use of decellularized adipose matrices (DAMs), an injectable off-the-shelf filler prepared from discarded lipoaspirate that preserves the macromolecular architecture and growth factors important for attenuating fibrosis. Therefore, this study evaluates the application of DAM and fat grafting in treating wounds after RIF.

Methods: Forty female C57BL/6 mice were allocated into four groups: irradiated wounds treated with 1) fat grafting, 2) DAM, 3) saline, and 4) a non-irradiated control. Wound healing was evaluated on postoperative days 1, 7, 14, and 21. Biomechanical testing, Laser Doppler blood flowmetry, and Hematoxylin and Eosin staining were performed.

Results: Both DAM and fat grafting exhibited improved elasticity and reduced stiffness upon wound closure, with tensile strength approaching that of non-irradiated skin. Additionally, irradiated skin demonstrated increased vascularity after DAM and fat grafting treatment compared to controls at later time points. No significant differences in the rate of wound healing and scar size were observed between DAM and fat grafting.

Conclusion: DAM serves as a promising noninvasive approach to enhance the regeneration of cutaneous wounds following RIF. Further modulation of anti-fibrotic fibroblast subpopulations may augment the regenerative capabilities of DAM for patients undergoing radiotherapy.