Application of Dental Pulp Stem Cell–Derived Intracellular Vesicles for Diabetic Wound Healing

Abstract

Diabetic wounds represent a significant clinical and economic burden, affecting both patients and health care systems. While current therapeutic approaches, such as negative pressure wound therapy, offer benefits, their limitations necessitate alternative strategies. Newly discovered dental pulp stem cell–derived intracellular vesicles have emerged as a promising candidate in regenerative medicine due to their therapeutic potential. In vitro assessments using HUVECs, HaCaTs, and RAW264.7 cells revealed that intracellular vesicles enhance cell migration, angiogenesis, and proliferation while suppressing the cGAS-STING pathway. Additionally, intracellular vesicles promoted M2 macrophage polarization and maintained mitochondrial function. In a diabetic mouse wound model, both intracellular vesicles and negative pressure wound therapy individually improved wound healing, but their combination exhibited a synergistic effect, resulting in faster wound closure, enhanced angiogenesis, and reduced inflammation. The combined treatment also exhibited excellent biocompatibility. These findings highlight the therapeutic potential of intracellular vesicles as an adjunct to negative pressure wound therapy for diabetic wound treatment. Article Highlights Chronic diabetic wounds are difficult to heal, and current treatments, such as negative pressure wound therapy, have limited effectiveness. The potential of intracellular vesicles derived from dental pulp stem cell lysate for diabetic wound healing is well worth exploring. Intracellular vesicles promoted angiogenesis, cell proliferation, and M2 macrophage polarization by inhibiting cGAS-STING signaling and restoring mitochondrial function. Combined with negative pressure wound therapy, intracellular vesicles accelerated wound healing in diabetic mice. Intracellular vesicles offer a promising cell-free strategy to enhance negative pressure wound therapy outcomes and improve diabetic wound treatment.