G3 - Modulation of Radiation-Induced Skin Fibrosis Using a Porcine-Derived ECM Biomaterial

Introduction: : Skin cancer is the most commonly diagnosed malignancy in the United States, affecting approximately 20% of the population over their lifetime. For non-melanoma skin cancers, radiotherapy is a frontline treatment, offering effective tumor control. Despite its clinical efficacy, radiotherapy often leads to adverse tissue remodeling, most notably radiation-induced fibrosis, which occurs in approximately 30–70% of patients and can severely diminish quality of life. This pathological process is characterized by aberrant collagen accumulation and disruption of extracellular matrix (ECM) homeostasis. To date, no clinically approved therapies have proven successful in preventing or reversing fibrosis following radiation exposure.
Our laboratory has developed a novel biomaterial derived from decellularized porcine laryngeal tissue that demonstrates both anti-inflammatory and antifibrotic activity, primarily by modulating the TGF-β1 signaling pathway, a central mediator in fibrotic disease. Building on these findings, the current study aims to investigate the efficacy of decellularized extracellular matrix (dECM) material in mitigating radiation-induced skin fibrosis.

Materials and

Methods: : To establish a fibrosis model, mice were exposed to graded doses of radiation (15–60 Gy) to generate a dose-response curve. Animals were randomized into six groups: five irradiated groups and one non-irradiated control. Skin injury was monitored weekly with photographs, and damage was scored using a semi-quantitative scale. Body weight was tracked weekly for three months. At the endpoint, skin samples were collected for histological analysis. Based on the severity of the injury, an optimal radiation dose was selected for the treatment phase.
In the treatment phase, animals will be randomized into three groups: a non-treated irradiated control group and two groups receiving the dECM biomaterial beginning one week prior to irradiation. Tissue samples collected at the study endpoint will undergo histopathological evaluation, including Masson’s trichrome staining to quantify collagen content. Expression of fibrotic markers, such as ACTA2, will be analyzed using quantitative real-time PCR (qRT-PCR).

Results, Conclusions, and Discussions:: fibrotic response, ACTA2, a marker of myofibroblast differentiation, will be quantified via qRT-PCR. Its expression serves as an indicator of ECM remodeling and fibrotic activity. Downregulation of ACTA2, along with reduced collagen observed by Masson’s trichrome staining, would suggest a therapeutic effect of the porcine dECM biomaterial. Preliminary in vitro data support the antifibrotic properties of this material, and we anticipate that treated animals will show attenuated fibrotic remodeling. These results provide a strong foundation for advancing dECM-based therapies for radiation-induced skin fibrosis.

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