Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. INTRODUCTIONSkin wound healing is an extremely complex process that involves the reactions and interactions of inflammatory cells, growth factors, and cytokines.1 This orchestrated process can be divided into four overlapped phases starting with hemostasis, followed by inflammation and proliferation, and ending by maturation, including collagen remodeling to restore the damaged skin integrity through formation of a mature scar.

Skin grafting is often the only treatment for skin trauma when large areas of tissue are affected. This surgical intervention damages the deeper dermal layers of the skin with implications for wound healing and a risk of scar development. Photobiomodulation (PBM) therapy modulates biological processes in different tissues, with a positive effect on many cell types and pathways essential for wound healing. This study investigated the effect of fluorescent light energy (FLE) therapy, a novel type of PBM, on healing after skin grafting in a dermal fibrotic mouse model. Split-thickness human skin grafts were transplanted onto full-thickness excisional wounds on nude mice. Treated wounds were monitored, and excised xenografts were examined to assess healing and pathophysiological processes essential for developing chronic wounds or scarring. Results demonstrated that FLE treatment initially accelerated re-epithelialization and rete ridge formation, while later reduced neovascularization, collagen deposition, myofibroblast and mast cell accumulation, and connective tissue growth factor expression. While there was no visible difference in gross morphology, we found that FLE treatment promoted a balanced collagen remodeling. Collectively, these findings suggest that FLE has a conceivable effect at balancing healing after skin grafting, which reduces the risk of infections, chronic wound development, and fibrotic scarring.