155. Decellularized Adipose Matrices and Fat Grafting in Wound Healing Following Radiation-induced Fibrosis

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PURPOSE: Radiation therapy has significantly improved mortality and remission rates for patients with cancer, yet radiation-induced fibrosis (RIF) remains a prevalent complication characterized by chronic ulceration, skin retraction, hypovascularity, and ischemic dermal necrosis. RIF induces apoptosis and fibroblast impairment, leading to delayed wound healing with no effective treatments currently available. While autologous fat grafting is a common strategy for partially reconstructing and regenerating irradiated tissue, it is limited by donor site availability. This limitation is especially significant for patients experiencing weight loss from chemotherapy and cancer, often requiring repeated grafting procedures. A promising alternative has been the application of decellularized adipose matrices (DAMs), an injectable off-the-shelf filler prepared from discarded lipoaspirate that retains most of the complex macromolecular network and growth factors that contribute towards attenuating fibrosis. Therefore, this study evaluates the application of DAM and fat grafting in enhancing wound healing in irradiated soft tissue and explores their effects on fibroblast subpopulations to elucidate regenerative mechanisms. METHODS: Forty eight-week-old female C57BL/6 mice were separated into four treatment groups: 1) irradiated wounds with fat grafting, 2) irradiated wounds with DAM, 3) irradiated wounds with saline injection, and 4) a non-irradiated control. A splinted excisional wound was created six weeks after dorsal irradiation to model human-like healing kinetics after RIF. Wound healing was evaluated using histological evaluation, including Hematoxylin and Eosin (H&E), Masson’s Trichrome, and Picrosirius Red staining. Biomechanical testing and Laser Doppler blood flowmetry were also performed at days 1 (inflammation), 7 (fibroblast proliferation), 14 (re-epithelialization), and 21 (wound closure). RESULTS: DAM and fat grafting treatments both demonstrated significant improvements in soft tissue regeneration. Irradiated skin treated with DAM or fat graft exhibited reduced dermal thickness, decreased collagen deposition, and improved organization of collagen fibers compared to the untreated controls. In addition, biomechanical testing demonstrated enhanced elasticity and reduced stiffness in the treated groups, with tensile strength closer to non-irradiated cutaneous tissue. DAM and fat grafting also improved wound vascularity compared to saline-treated controls. CONCLUSIONS: DAM serves as a promising noninvasive strategy to promote regeneration of cutaneous wounds following RIF. Modulating anti-fibrotic fibroblast subpopulations may further enhance the regenerative potential of DAM and enable improved healing outcomes for cancer patients undergoing radiotherapy.

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