Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model

Abstract

Background Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. Methods We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. Results The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. Conclusion Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

Efficacy of tibial cortex transverse transport in treating diabetic foot ulcer and its effect on serum omentin-1 and irisin levels

“…Earlier works have endeavored to dig out the mechanism explaining the treatment effect of TTT for DFUs, involving enhanced angiogenesis and inflammation modulation [ 33 , 34 ]. In these works, the diabetic rat model with induced hindlimb ischemia presented marked neovascularization accompanying with upregulation of angiogenic factors, such as SDF-1 and CXCR4.…”

Efficacy of MSC-derived small extracellular vesicles in treating type II diabetic cutaneous wounds: a systematic review and meta-analysis of animal models

“…Impaired macrophage function constitutes a significant etiologic factor underlying the chronic inflammation observed in individuals with T2DM ( 57 – 59 ). The outcomes from our meta-analysis clearly demonstrate that treatment with MSC-sEVs results in a notable reduction in IL-6, a prominent proinflammatory factor, while concomitantly elevating the expression of IL-10, a well-established anti-inflammatory marker.…”