A Novel Murine Model for Studying Impaired Wound Healing in Diabetes.

Abstract

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&#x2009;weeks and injected with three doses of streptozotocin (65&#x2009;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&#x2009;=&#x2009;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&#x2009;&#xb1;&#x2009;5.4&#x2009;mmol/L vs. 8.7&#x2009;&#xb1;&#x2009;0.8&#x2009;mmol/L) and lower wound quality scores (day-4 post-wounding: 2.6&#x2009;&#xb1;&#x2009;1.9 vs. 4.4&#x2009;&#xb1;&#x2009;0.8) than healthy controls (both p&#x2009;<&#x2009;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.