A Model to Study Wound Healing Over Exposed Avascular Structures in Rodents With a 3D-Printed Wound Frame

Abstract

Background: Soft tissue defects with exposed avascular structures require reconstruction with well-vascularized tissues. Extensive research is ongoing to explore tissue engineered products that provide durable coverage. However, there is a lack of controlled and affordable testbeds in the preclinical setting to reflect this challenging clinical scenario. We aimed to address this gap in the literature and develop a feasible and easily reproducible model in rodents that reflects an avascular structure in the wound bed.

Methods: We created 20 × 20 mm full thickness wounds on the dorsal skin of Lewis rats and secured 0.5-mm-thick silicone sheets of varying sizes to the wound bed. A 3D-printed wound frame was designed to isolate the wound environment. Skin graft and free flap survival along with exposure of the underlying silicone was assessed. Rats were followed for 4 weeks with weekly dressing changes and photography. Samples were retrieved at the endpoint for tissue viability and histologic analysis.

Results: The total wound surface area was constant throughout the duration of the experiment in all groups and the wound frames were well tolerated. The portion of the skin graft without underlying silicone demonstrated integration with the underlying fascia and a histologically intact epidermis. Gradual necrosis of the portion of the skin graft overlying the silicone sheet was observed with varying sizes of the silicone sheet. When the size of the silicone sheet was reduced from 50% of the wound surface area, the portion surviving over the silicone sheet increased at the 4-week timepoint. The free flap provided complete coverage over the silicone sheet.

Conclusion: We developed a novel model of rodent wound healing to maintain the same wound size and isolate the wound environment for up to 4 weeks. This model is clinically relevant to a complex wound with an avascular structure in the wound bed. Skin grafts failed to completely cover increasing sizes of the avascular 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.