Remote periosteal distraction promotes ischemic diabetic foot wound repair associated with VEGF/VEGFR2-related angiogenic responses.

Bone transport-induced remote microinjury may promote diabetic foot ulcer healing but requires osteotomy and may cause fracture or osteomyelitis. This study evaluated whether osteotomy-free remote periosteal distraction (RPD) could promote repair in a rabbit ischemic diabetic foot wound model. Seventy-two diabetic male rabbits were randomized into RPD, Sham, and Control groups, and ischemic foot wounds were created. In the RPD group, a custom-made plate was implanted beneath the tibial periosteum and connected to an external distractor. The periosteum was distracted outward for 7 days and returned inward for another 7 days. Sham animals underwent the same implantation procedure without device adjustment, whereas Control animals received wound creation alone. Wound closure, histological changes, vascular parameters, and angiogenesis-related markers were evaluated. On days 8 and 16, RPD resulted in a smaller residual wound area than the Control and Sham groups. RPD increased epithelial thickness and collagen deposition compared with the Control and Sham groups. RPD was associated with increased serum VEGF levels, higher VEGF mRNA expression, and larger CD31-, VEGF-, and VEGFR2-positive areas in wound tissues. On day 16, ex vivo micro-CT angiography demonstrated higher vascular volume in the wound region after RPD treatment. Osteotomy-free RPD promoted wound repair in an ischemic diabetic wound model. These effects were associated with enhanced neovascularization and increased VEGF and VEGFR2 expression at the wound site. RPD may represent a potentially less invasive alternative to osteotomy-based tibial distraction for improving ischemic diabetic ulcer healing, but further mechanistic, safety, and clinical studies are required.