Transverse tibial transport accelerated of diabetic wound healing via enhanced Wnt/β-catenin-driven BMSCs mobilization and angiogenesis.

BACKGROUND

The management of severe diabetic foot ulcers (DFUs) remains a major clinical challenge. Tibial cortex transverse transport (TTT) has emerged as an effective surgical intervention, but its underlying mechanism, particularly concerning stem cell mobilization and signaling pathways, is largely unknown.

METHODS

A diabetic DFU model was established in New Zealand white rabbits using Streptozotocin (STZ), followed by TTT surgery. Wound healing was evaluated through photography, H&E, and Masson's trichrome staining. Angiogenesis was assessed by high-resolution X-ray angiography and immunofluorescence. Bone marrow-derived mesenchymal stem cell (BMSC) mobilization was analyzed via CFU-F assays and flow cytometry. Serum levels of SDF-1α, CXCR4, VEGF, and Ang2 were measured by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The activity of the Wnt/β-catenin pathway was determined by Western blot.

RESULTS

Tibial cortex transverse transport significantly accelerated wound closure and enhanced tissue regeneration, with improved epidermal/dermal restoration and collagen deposition. Consistently, neovascularization in wounds was markedly promoted. Mechanistically, TTT activated the Wnt/β‑catenin signaling pathway in BMSCs, which was associated with enhanced BMSC quantity, mobilization, and migration capacity. Inhibition of this pathway attenuated the TTT‑induced pro‑healing effects.

CONCLUSION

Tibial cortex transverse transport promotes healing of DFUs primarily by activating the Wnt/β-catenin pathway in BMSCs, thereby enhancing their mobilization, homing, and pro-angiogenic capacity. This study reveals a key molecular mechanism underlying TTT's efficacy and supports its therapeutic potential for refractory Diabetic foot ulcer (DFU).