This study demonstrates that intermittent fasting and PRFE combination therapy enhance diabetic wound healing, effectively leveraging the strengths of both therapies and even yielding synergistic benefits. Moreover, it indicates the potential engagement of the P75/HIF1A/VEGFA axis in mediating these effects.

In vivo experiments involved the induction of diabetic models in C57 mice through streptozotocin injection. To simulate a combined therapeutic approach, diabetic mice underwent fasting on days 2 and 6, accompanied by twice daily PRFE applications for 8 days. In vitro experiments were conducted using a serum-free culture medium to replicate fasting conditions. The investigation encompassed wound healing rate, proliferation, migration, angiogenesis, oxidative stress, fibrogenesis, and sensory nerve growth through histological analysis and functional assessments in vivo. Additionally, this study utilized quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting (WB), and immunofluorescence staining techniques to elucidate the potential mechanisms underlying the effects of intermittent Fasting and PRFE combination therapy in diabetic wound healing, both in vitro and in vivo.

This study aims to conduct an unbiased assessment of the synergistic effects of non-pharmacological Interventions of intermittent fasting and pulsed radiofrequency energy (PRFE) combination therapy on the facilitation of diabetic wound healing, while also exploring the underlying mechanisms. The findings of this research will provide a theoretical framework and innovative strategy for unconventional therapeutic interventions aimed at enhancing the healing process of diabetes-related wounds.

The intermittent fasting and PRFE combination therapy demonstrated superior efficacy in enhancing diabetic wound healing compared to either treatment alone. It harnessed the respective strengths of individual therapies, fostering migration, mitigating oxidative stress, and enhancing fibrogenesis. Furthermore, the combination therapy manifested a synergistic effect in promoting proliferation, tube formation, angiogenesis, and sensory nerve growth.