A Novel Murine Model for Studying Impaired Wound Healing in Diabetes

A lack of murine models that mimic impaired wound healing in people with type 2 diabetes has hindered research. The commonly used leptin‐receptor knockout model (db/db) fails to accurately reflect the pathophysiology of human disease. This study aimed: (i) to investigate whether our novel murine model of diabetes, whilst less hyperglycaemic and obese than db/dbs, effectively demonstrated impaired wound healing, and (ii) to identify the most robust methods for quantifying wound closure. C57BL/6J mice were high‐fat diet fed for a total of 11 weeks and injected with three doses of streptozotocin (65 mg/kg body weight) at week 5 with chow‐fed mice as controls. All mice received four excisional wounds and were euthanised at day‐4 or day‐10 post‐wounding ( n = 8/group/timepoint). Wound healing was evaluated by digital planimetry, histology, Micro‐CT, and tensiometry. Histological analysis was the most sensitive method for identifying impaired wound healing. Our high‐fat diet/low‐dose streptozotocin model had significantly higher non‐fasting blood glucose (25.7 ± 5.4 mmol/L vs. 8.7 ± 0.8 mmol/L) and lower wound quality scores (day‐4 post‐wounding: 2.6 ± 1.9 vs. 4.4 ± 0.8) than healthy controls (both p < 0.05). At day‐10 post‐wounding, a linear trend in wound healing was observed between healthy controls, our novel model and the db/db model, indicating that our diabetic murine model may be clinically relevant for studying diabetes‐related wound healing.