Bone transport induces CGRP release from sensory nerves to promote angiogenesis and heal diabetic foot wounds in rats

Diabetic foot ulcer (DFU) is a critical complication of diabetes, characterized by high recurrence rates, high disability rates, high mortality, and a significant socioeconomic burden. The tibial cortex transverse transport therapy, based on the tension-stress effect, has demonstrated significant efficacy in promoting the healing of DFUs; however, its underlying mechanisms remain incompletely elucidated. Recent evidence show calcitonin gene-related peptide (CGRP) is important for tissue regeneration.

However, its role in BT-mediated healing is still unknown. This study aimed to investigate whether and how sensory nerves participate in the process of BT-promoted DFU healing via the release of CGRP. A femoral BT model was established in diabetic rats, with concurrent creation of an ischemic and dorsal foot wound model on the ipsilateral hindlimb.

Capsaicin was employed to ablate sensory nerves and block CGRP release. Animals were allocated into four groups: sham-operated group, external fixator group, BT group, and BT + capsaicin group. Wound healing rate, angiogenesis, and CGRP expression in the DRG and regenerated skin were assessed.

Transcriptomic analysis was performed on healed skin tissue. In vitro, the effects of CGRP on tube formation ability, as well as on the expression of CD31, VEGFA, and FAK phosphorylation, were evaluated in HUVECs. The BT technique significantly promoted the healing of dorsal foot wounds in diabetic rats (P