Topical Administration of a Marine Oil Rich in Pro-Resolving Lipid Mediators Accelerates Wound Healing in Diabetic db/db Mice through Angiogenesis and Macrophage Polarization

Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA(R) is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA(R) in wound dressing applications. LIPINOVA(R) showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (M phi 1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and M phi 1/M phi 2 macrophage polarization. In conclusion, LIPINOVA(R) displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.