Platelet-rich fibrin combined with naringin accelerates diabetic wound healing by enhancing re-epithelialization and reducing inflammation.

Delayed wound healing, one of the fatal complications that affect about 15% of diabetic patients, is associated with impaired keratinocyte proliferation and migration and enhanced inflammation. In this research, we investigated the combined application of platelet-rich fibrin (PRF) and the natural flavonoid naringin for wound healing in diabetic conditions. High glucose (HG)-stimulated human keratinocytes HaCaT and high fat diet + streptozotocin-induced diabetic rats were treated with PRF and naringin alone or in combination. HaCaT cell proliferation and migration were detected by EdU staining and wound healing assay. On days 0, 3, 7, and 14 after wound creation, the wound healing rates in diabetic rats were calculated. The combined treatment of PRF and naringin was more effective than PRF or naringenin alone in enhancing cell proliferation and migration and attenuating MMP2/9 and pro-inflammatory cytokine expression in HG-exposed HaCaT cells. PRF and naringin combination exhibited higher efficacy in accelerating wound closure, elevating cell proliferation, and reducing inflammation and NF-κB phosphorylation in rat wound tissues vs. PRF or naringin treatment alone. In conclusion, the combined treatment of PRF and naringin is more effective than either treatment alone in promoting the healing of diabetic wounds through enhancing wound re-epithelialization and alleviating inflammation.