H. Z. Masri1, E. Ebirim1, M. Dawar1, N. Anika1, P. Bommekal1, H. Li1, L. Yu1, S. Pixley2, S. Balaji1 1Baylor College Of Medicine, Pediatric Surgery, Houston, TX, USA 2University Of Cincinnati, College Of Medicine, Pharmacology & Systems Physiology, Cincinnati, OH, USA
Introduction: Magnesium (Mg) is a co-factor for critical enzymes important in wound healing and has anti-inflammatory, anti-bacterial, and tissue remodeling effects. Biodegradable Mg metal alloys can promote wound healing by both releasing Mg ions and hydrogen gas (H2) with antioxidant properties. 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 and degradation rate for dermal wound healing application. We hypothesize that Mg metal devices will provide physical guidance during the early phases of wound closure and promote regenerative tissue remodeling.
Methods: Mg alloy fine wires (WE43B, 127 µm, 90% cold work [CW], and 250°C heat treated) were cut to 5mm length and 5 wires were placed in each 6mm stented dorsal skin wounds in C57BL/6J mice (n=6, F, 8 weeks) (Fig. 1a). PBS was put on an identical wound on the opposite side of the back as an internal control. Wounds were covered in a semi-permeable dressing (Tegaderm™) and harvested on day 7 and day 28. Metal degradation was assessed at d7 and d28 (microCT). Wound sections were stained with Hematoxylin and Eosin and epithelial gap and granulation tissue were measured at d7. Scar area, collagen accumulation (Picro Sirius red), epithelial regeneration, and dermal appendages were analyzed at d28. P values by ANOVA.
Results: All mice tolerated Mg wire placement. Gross imaging on alternate days showed no difference in inflammatory reaction and exudate compared to PBS. Mg wires were visible in the wounds at day 7 and micro-CT imaging showed minimal metal degradation (Fig. 1b). At d28 there was a significant degradation (Fig. 1c), suggesting Mg wire degradation kinetics appropriate for use in wound healing. At d7 post wounding, there was no difference in epithelial gap closure, but Mg treatment significantly improved granulation tissue area compared to PBS (0.56+/-0.19 vs 0.29+/-0.09 sq mm, p<0.001). At 28 days, 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. 1d).
Conclusion: Our data demonstrate that Mg metal wires promote regenerative dermal wound healing without adverse inflammatory reactions. These studies provide a strong rationale to harness Mg metal use in wound healing applications, especially to treat infected or chronic wounds without creating adverse responses that could materialize in antibody resistance or rejection of the treatments.
