Prophylactic Decellularized Adipose Matrix Treatment Mitigates Development of Radiation-Induced Cutaneous Fibrosis

Radiation therapy is an effective and common cancer therapy, but it often results in the formation of radiation-induced fibrosis (RIF). RIF of the skin manifests as symptoms including erythema, ulceration, hypovascularity, and poor wound healing. Subdermal injection of decellularized adipose matrix (DAM) has been studied as a potential means of correcting volumetric deficiencies while imparting regenerative effects to the overlying skin in patients with cutaneous RIF. DAM was injected subdermally to the flank region of adult C57BL/6J mice and irradiation was then applied to this area. Irradiated mice were given 4 weeks after completion of the irradiation protocol to allow for development of chronic RIF. Magnetic resonance imaging studies were performed throughout the recovery interval to monitor volume retention of the product. Longitudinal laser Doppler studies were used to follow perfusion. After experimental completion, flank skin was harvested and underwent histological and biomechanical evaluation. Histological staining with hematoxylin and eosin, Masson's trichrome, and picrosirius red stains demonstrated that irradiated skin architecture more closely resembled normal skin across measures of dermal thickness, collagen density, and collagen organization when DAM was injected prophylactically. Magnetic resonance imaging revealed that DAM volume retention decreased over time. Laser Doppler demonstrated improved perfusion of irradiated skin with prior DAM injection. Finally, biomechanical testing demonstrated that prophylactic DAM administration resulted in reduced skin stiffness compared to irradiated skin without DAM. This study reveals the therapeutic potential of prophylactic DAM treatment to prevent formation of RIF in skin. Our findings demonstrate that injected DAM volume is largely retained following irradiation and results in overlying skin retaining histologic and biomechanical characteristics of normal nonirradiated skin.