(618b) Local Sustained Knockdown for Accelerated Diabetic Wound Healing

Diabetic foot ulcers (DFUs) affect more than one million Americans annually, costing nearly 11 billion dollars a year in healthcare spending and leading to over 70,000 lower limb amputations.  These wounds are painful, nagging injuries that significantly reduce the quality of life for patients and their families.  To date most pharmacological approaches to DFU therapy focuses on the delivery of super-physiological concentrations of recombinant growth factors, which has shown only limited success with serious side-effects.  In this work we report the use of layer-by-layer technique to effectively deliver short interfering RNA (siRNA) directly to the wound bed in a diabetic mouse model of chronic wound healing.  We targeted the expression of ECM protease MMP-9, known to be chronically upregulated in the wounds of diabetic patients and diabetic wound healing models.  It was observed that MMP-9-specific siRNA therapy led to reduced MMP-9 expression and to significant improvements in wound healing, with increased granulation tissue formation and accelerated epithelial closure.  This work points to a new focus in localized RNAi therapy, where dysregulated and pathologic gene expression can be directly targeted and corrected.