The direct local delivery of short interfering RNA (siRNA) to tissues may present solutions to several complex medical conditions. In particular, chronic wound healing is a serious and painful complication of diabetes mellitus (DM) affecting as many as one in four patients with a three year recurrence rate of more than 50% and leaving over 70,000 patients in the United States alone facing amputation. Here we describe the use of siRNA delivered locally into the diabetic ulcer directly and in a sustained fashion to knockdown a chronically upregulated extracellular matrix protease, matrix metalloproteinase-9 (MMP-9), to improve wound healing. A self-assembled polymer thin film coating, when applied conformally to commercially available nylon bandages, sustains the delivery of small interfering RNA (siRNA) into the wound bed while maintaining activity and facilitating transfection. This approach reduces protein expression and enzyme activity within the wound for over two weeks, leading to a significant improvement in chronic wound healing.