Development of translational murine soft tissue defect model for wound healing research

Extensive soft tissue defects involving loss of skin, fat, and muscle often result from trauma or tumor resection. Current treatments, including autografts and flaps, are limited by donor-site morbidity and scarce tissue availability. Animal models, particularly in rodents, are essential for research but are limited by their primary healing mechanism—contraction via the panniculus carnosus—which does not accurately reflect human healing. Furthermore, standardized models for complex skin–muscle defects are lacking. Therefore, this study aims to create a clinically relevant composite soft tissue defect model in mice using a three-dimensional (3D) polylactic acid (PLA) chimney splint to inhibit contraction and better mimic human wound healing mechanisms (re-epithelialization and granulation tissue formation). A composite defect was created on the dorsum of 8-week-old BALB/c nude mice. The biocompatibility of the 3D-printed PLA chimney was assessed via MTT assay. In vivo, fixation methods—tissue adhesive (TA), simple interrupted sutures (SI), and purse-string suture (PS)—were compared. Wound healing was evaluated over 4 weeks via gross and histological analyses. PLA material showed excellent biocompatibility in vitro, with cell viability consistently above 85%, indicating noncytotoxicity. In vivo, the TA and SI groups showed severe inflammation, tissue necrosis, and splint detachment. In contrast, the PS group remained stable for 4 weeks with no complications. Histologically, the PS group effectively suppressed contraction. Re-epithelialization from the wound edge, well-organized granulation tissue with active angiogenesis, abundant fibroblasts, and collagen deposition, and spindle-shaped cells were clearly observed. In conclusion, this study establishes a reproducible and stable murine composite soft tissue defect model by combining a 3D-printed chimney splint with a PS technique. This model overcomes a key limitation of rodent wound models by controlling contraction, offering a robust preclinical platform to study composite tissue healing and evaluate next-generation regenerative medicine therapies.