Background Radiation-induced skin injury is a well-known risk factor for impaired wound healing. Over time, the deleterious effects of radiation on skin produce a fibrotic, hypovascular dermis poorly suited to wound healing. Despite increasing understanding of the underlying pathophysiology, therapeutic options remain elusive. Deferoxamine (DFO), an iron-chelating drug, has been shown in prior murine studies to ameliorate radiation-induced skin injury as well as improve wound healing outcomes in various pathologic conditions when administered transdermally. In this preclinical study, we evaluated the effects of deferoxamine on wound healing outcomes in chronically irradiated murine skin. Methods Wild-type mice received 30 Gy of irradiation to their dorsal skin and were left to develop chronic fibrosis. Stented excisional wounds were created on their dorsal skin. Wound healing outcomes were compared across 4 experimental conditions: DFO patch treatment, vehicle-only patch treatment, untreated irradiated wound, and untreated nonirradiated wounds. Gross closure rate, wound perfusion, scar elasticity, histology, and nitric oxide assays were compared across the conditions. Results Relative to vehicle and untreated irradiated wounds, DFO accelerated wound closure and reduced the frequency of healing failure in irradiated wounds. DFO augmented wound perfusion throughout healing and upregulated angiogenesis to levels observed in nonirradiated wounds. Histology revealed DFO increased wound thickness, collagen density, and improved collagen fiber organization to more closely resemble nonirradiated wounds, likely contributing to the observed improved scar elasticity. Lastly, DFO upregulated inducible nitric oxide synthase and increased nitric oxide production in early healing wounds. Conclusion Deferoxamine treatment presents a potential therapeutic avenue through which to target impaired wound healing in patients following radiotherapy.

Hypertrophic scar formation and non-healing wounds following Achilles tendon repair arise from poor vascularity to the incisional site or from excess mechanical stress/strain to the incision during the healing process. The embrace® scar therapy dressing is a tension offloading device for incisional scars. This study explored the effects of tension offloading during Achilles scar formation. A healthy 30-year-old male without any medical co-morbidities developed an acute rupture of his left Achilles tendon. The patient underwent open repair 1 week after injury. At post-operative day (POD) 14, the patient started daily tension offloading treatment on the inferior portion of the incision through POD 120. By POD 120, the untreated portion of the Achilles incision appeared hypertrophic and hyperpigmented, while the treated portion of the scar appeared flat with minimal pigmentation changes. The 12-week treatment of tension offloading on an Achilles tendon repair incision significantly improved cosmesis compared to untreated incision.

Background: A significant gap exists in the translatability of small-animal models to human subjects. One important factor is poor laboratory models involving human tissue. Thus, the authors have created a viable postnatal human skin xenograft model using athymic mice. Methods: Discarded human foreskins were collected following circumcision. All subcutaneous tissue was removed from these samples sterilely. Host CD-1 nude mice were then anesthetized, and dorsal skin was sterilized. A 1.2-cm-diameter, full-thickness section of dorsal skin was excised. The foreskin sample was then placed into the full-thickness defect in the host mice and sutured into place. Xenografts underwent dermal wounding using a 4-mm punch biopsy after engraftment. Xenografts were monitored for 14 days after wounding and then harvested. Results: At 14 days postoperatively, all mice survived the procedure. Grossly, the xenograft wounds showed formation of a human scar at postoperative day 14. Hematoxylin and eosin and Masson trichome staining confirmed scar formation in the wounded human skin. Using a novel artificial intelligence algorithm using picrosirius red staining, scar formation was confirmed in human wounded skin compared with the unwounded skin. Histologically, CD31+ immunostaining confirmed vascularization of the xenograft. The xenograft exclusively showed human collagen type I, CD26+, and human nuclear antigen in the human scar without any staining of these human markers in the murine skin. Conclusion: The proposed model demonstrates wound healing to be a local response from tissue resident human fibroblasts and allows for reproducible evaluation of human skin wound repair in a preclinical model. Clinical Relevance Statement: Radiation-induced fibrosis is a widely prevalent clinical phenomenon without a well-defined treatment at this time. This study will help establish a small-animal model to better understand and develop novel therapeutics to treat irradiated human skin.

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