N. N. Anika1, A. Nagi1,3, L. N. Yu1, S. Pixley2, S. Balaji1 1Baylor College of Medicine and Texas Children’s Hospital, Pediatric Surgery, Houston, TX, USA 2University of Cincinnati College of Medicine, Pharmacology & Systems Physiology, Cincinnati, OH, USA 3HSPVA High School, Houston, TX, USA
Introduction:
Magnesium (Mg) is co-factor for critical enzymes important in wound healing. Biodegradable Mg metal alloys can promote wound healing by releasing Mg ions. We optimized alloy chemistry and thermomechanical processing conditions to manufacture fine Mg wire with sufficient mechanical properties to withstand wound implantation and in-service loading with excellent tissue tolerance. We hypothesize that Mg metal devices will provide physical guidance during early phases of wound closure and promote neovascularization, neuronal Growth and wound regenerationregenerative tissue remodeling.
Methods:
Mg alloy wires (WE43B, 127 uµm, 90% cold work, and 250°C heat treated) were cut to 6mm length, and 5 wires were placed in 6mm stented full-thickness flank skin wound in C57BL/6J mice (n=6, F, 8 weeks) (Fig. 1a). Contralateral flank wound was treated with PBS as internal control. Wound sections were stained with H&E to measure epithelial gap and granulation tissue at d7; neovascularization (CD31), leucocyte and macrophage infiltration (CD45; F4/80), and neurons (tuj1) were assessed. Scar area, collagen density, epithelial thickness and dermal appendages were analyzed at d28. P values by ANOVA.
Results:
All mice tolerated Mg wire placement. Gross imaging showed no difference in exudate compared to PBS. Mg wires were visible at d7 (Fig. 1b) and d28 (Fig. 1c), suggesting Mg wire degradation appropriate for use in wound healing. At d7 there was no difference in epithelial gap closure, but Mg significantly improved granulation tissue (0.56±0.19 vs 0.29±0.09 mm2, p<0.001) (Fig. 1d-e). Mg also reduced inflammatory cell infiltration of both leukocytes (21.4±4.3 vs 34.1±5.1 cells/HPF, p<0.01) (Fig. 1f) and macrophages (27.1±4.1 vs 50.1±7.5 cells/HPF, p<0.01) (Fig. 1g), and improved wound neovascularization (21.2±5.7 vs 12.7±4.3 lumens/HPF, p<0.01) (Fig. 1h) and tuj1 fluorescence expression ((Fig. 1i) compared to PBS. At d28, a very small scar remained in Mg wounds. Scar area was reduced, with improvement in ECM organization and subepithelial nuclear counts (fibroblasts) and dermal appendages in Mg wounds (Fig. 1j).
Conclusion:
Our data demonstrate that Mg metal wires reduce inflammation and promote granulation tissue formation, neovascularization and neuron growth early in wound healing to support regenerative dermal wound healing. This provides a strong rationale to harness Mg metal use in wound healing applications, specially to treat infected or chronic wounds without creating adverse responses such as antibody resistance or rejection of the treatments.
