(WHS-K4.06) BIODEGRADABLE MAGNESIUM WIRES PROMOTE NEOVASCULARIZATION AND NEURONAL GROWTH FOR WOUND REGENERATION
Thursday, May 16, 2024
9:15 AM – 10:15 AM East Coast USA Time
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 regeneration. Mg alloy wires (WE43B, 127 µm, 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 wounds in C57BL/6J mice (n=6, F, 8 weeks). Contralateral flank wound was treated with PBS as an 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 at d7. Scar area, collagen density, lumen density, epithelial thickness and dermal appendages were analyzed at d28. MicroCT was performed at d7 and d28 to see Mg wires. p values by ANOVA. All mice tolerated Mg wire placement. Gross observation showed no difference in exudate compared to PBS. Mg wires were visible at d7 and microCT revealed very small fragments even at d28, suggesting Mg wire degradation was appropriate to support all phases of 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). Mg also reduced inflammatory cell infiltration of both leukocytes (21.4±4.3 vs 34.1±5.1 cells/HPF, p<0.01) and macrophages (27.1±4.1 vs 50.1±7.5 cells/HPF, p<0.01), and improved wound neovascularization (21.2±5.7 vs 12.7±4.3 lumens/HPF, p<0.01) and tuj1 fluorescence expression compared to PBS. At d28, a very small scar remained in Mg wounds. Scar area was reduced in Mg wounds, with improvement in ECM organization and subepithelial nuclear counts in papillary dermis, significantly increased lumen density (16±3.6 vs 11.5±1.7 lumens/HPF, p<0.05) and dermal appendages. 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.