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The Effect of Magnesium Salts on Peripheral Nerve Repair with Magnesium Microfilaments
Tracy Hopkins, MS; Kevin J. Little, MD; David Hom, MD; Sarah Pixley, PhD
University of Cincinnati, Cincinnati, OH
Introduction: Peripheral nerve injuries resulting in an unrepairable nerve gap are difficult to treat. Currently available biomaterial solutions are hollow nerve conduits, but these conduits are effective only for nerve gaps of < 3 centimeters. Bioresorbable magnesium (Mg) metal microfilaments have been shown previously to improve nerve regeneration, but are limited by rapid absorption. The addition of magnesium salts may carry the same beneficial effects towards nerve regeneration, and may also limit the speed of microfilament resorption in vivo. To test this hypothesis, we repaired 10 mm gaps in rat sciatic nerves using silicone conduits filled with magnesium microfilaments and saline or magnesium salts (2 mM MgSO4 in saline).
Materials and Methods: 10 mm nerve gaps were created in the sciatic nerves of adult male Lewis rats, and divided into 4 groups of 6 rats each. Silicone nerve conduits were sutured into the gaps and were filled with Mg microfilaments (99.9% pure, 250µm diameter): 1) empty conduit with saline filler, 2) Mg filament plus saline, 3) empty conduit with Mg salts (2 mM MgSO4 in saline), or 4) Mg filament plus Mg salts. After sacrifice at 6 weeks, nerves were removed, fixed, imaged by iodine-enhanced micro computed-tomography (microCT) then either paraffin embedded, sectioned and stained with H&E, or osmicated, embedded in resin, sectioned and stained with toluidine blue.
Results: In empty guides filled at surgery with saline or MgSO4, significant tissue strands, with myelinated axons, formed in 5/6 animals at 6 weeks after surgery, as shown by iodine contrast-enhanced micro computed tomography followed by histology. In guides with saline and a magnesium wire, only 2/6 animals, showed tissue strands. But in guides with MgSO4 solution and the magnesium wire, the number increased back to 5/6 animals with tissue strands. Myelinated axons in mini-fascicles that are typical of regenerating nerves were detected in all tissue strands that were intact across the gaps.
Conclusion: Increasing the concentration of magnesium ions at the time of magnesium metal implantation has a beneficial effect on nerve repair using magnesium metal wire. Magnesium ions may improve cell attachment to the microfilament, as the ions are known to be important for integrin function and cell attachment. Further testing to evaluate the most effective concentrations of magnesium salts is planned.
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