A Novel Model to Study Wound Healing Over Exposed Critical Structures in Rodents with a 3D-Printed Wound Frame
Fuat Baris Bengur, MD; Chiaki Komatsu, MD; Benjamin K. Schilling, PhD; Mario G. Solari, MD
University of Pittsburgh, Department of Plastic Surgery
Background: Soft tissue defects with exposed critical structures usually require reconstruction with well-vascularized tissues. Skin grafts and biological wound matrices are initially completely dependent on nutrients absorbed from the wound bed and often inadequate to provide durable coverage because of the lack of blood supply from the wound bed in complex wounds. Current animal models to evaluate these materials in a clinically relevant avascular wound bed are inadequate or not easily reproducible. We aimed to develop an affordable rodent model to demonstrate the efficacy of non-vascularized materials over a poorly vascularized wound bed.
Methods: We created 20x20 mm full thickness wounds on the dorsal skin of Lewis rats and secured 1-mm thick silicone sheets sized 15-50% of the wound’s surface area. A similarly sized 3D-printed wound contraction frame was placed around the wound bed to isolate. Either 1) split thickness skin graft, 2) single layer bovine tendon collagen and glycosaminoglycan dermal matrix, or 3) porcine urinary bladder matrix was used to cover the silicone sheet inside the wound frame. Additional groups with a free flap and skin graft without an underlying silicone served as controls for the model. The rats were followed for 4 weeks with weekly dressing changes and photography. Samples were retrieved at the endpoint for histologic analysis.
Results: The total wound surface area was constant during the experiment in all groups. Gradual necrosis of the skin graft and dermal matrices that corresponds to the silicone sheet was observed with eventual complete necrosis and exposure at the 4-week endpoint. The free flap provided complete coverage over the silicone sheet. The portion of the skin graft without the underlying silicone also demonstrated coverage and histologically integrated epidermis. All experimental groups had similar viability, whereas skin graft controls without the silicone sheet demonstrated 100% graft take (p<0.001). When the size of the silicone sheet was reduced from 50% of the wound surface area, the portion surviving over the silicone sheet increased.
Conclusion: We developed a novel model of rodent wound healing that prevents contracture and isolates the wound environment in a clinically relevant complex wound environment. The model was able to maintain the same wound size up to 4 weeks. Skin graft and dermal matrices failed to cover the exposed structure, whereas the free flap was able to provide viable coverage. This cost-effective model will establish an easily reproducible platform to evaluate more complex bioengineered wound coverage solutions.
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