A.Z. Fazilat1, C.E. Berry1, C. Brenac1, C. Kendig1, T. Le1, M. Griffin1, J. Guo1, L. Kameni1, R. Nazerali1, M.T. Longaker1, D.C. Wan1 1Stanford University, Plastic And Reconstructive Surgery/Surgery/Stanford University School Of Medicine, Palo Alto, CA, USA
Introduction: 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 injections 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.
Methods: Adult C57BL/6J (8-12 weeks) mice were separated into three conditions: 1) non-irradiated, untreated skin, 2) Irradiated, untreated skin, and 3) Irradiated, DAM-treated skin (Figure 1A). DAM was injected subdermally to the flank region of mice and irradiation was applied to this area exclusively. Irradiated groups were given 4 weeks after completion of the irradiation protocol to allow for the formation of chronic RIF. MRI studies were performed throughout the healing interval for groups treated with DAM to monitor the volume retention of the product. Laser doppler was performed to assess the vascularization (Figure 1B). Following experimental completion, flank skin was harvested and underwent histological and biomechanical evaluation.
Results: Histological staining with H&E, Masson’s trichrome, and picrosirius red stains demonstrated that skin architecture more closely resembling that of normal skin was maintained across measures of dermal thickness, collagen density, and collagen organization by prophylactic injection of DAM to the irradiated area (Figure 1C-D). MRI monitoring demonstrated that DAM volume retention was not affected by irradiation. Biomechanical testing demonstrated that prophylactic DAM injection resulted in the strength of irradiated overlying skin more similar to that of normal skin.
Conclusion: This study introduces the therapeutic potential of prophylactic DAM treatment to prevent the formation of RIF in the skin. Our results demonstrate that injected DAM volume is largely retained following irradiation and results in overlying skin retaining histologic and biomechanical characteristics of normal skin.