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Magnesium Microfilaments inside Traditional Nerve Conduits Improve Nerve Regeneration Characteristics
Kevin J. Little, MD1; Tracy Hopkins2, Alex Heilman3; Meir Hershcovitch, MD4; David Hom, MD4; Sarah Pixley, PhD2
1Department of Orthopaedic Surgery, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH; 2Department of Molecular and Cellular Biology, University of Cincinnati, Cincinnati, OH; 3School of Medicine, Vanderbilt University, Nashville, TN; 4Department of Otolarygology Head and Neck , University of Cincinnati, Cincinnati, OH
Introduction: The use of biomaterials for the reconstruction of long nerve gaps lacks clinical efficacy using current techniques. The placement of filaments inside traditional conduits has been proposed to provide physical support to guide cells across the gap. We have previously used magnesium (Mg) metal microfilaments as “cables” to act as physical support for nerve regeneration and as biodegradable implants that release Mg++ ions. We now test the hypothesis that Mg metal microfilaments can assist nerve regeneration across longer nerve gaps.
Materials & Methods: Short or long (6 or 15 mm) nerve gaps were created in the sciatic nerves of 44 adult male Lewis rats. Poly(caprolactone) nerve conduits were sutured into the gaps and filled with Mg microfilaments (99.9% pure, 250µm diameter), titanium microfilaments (250µm diameter) or saline filler alone (empty). Groups were: 1) empty conduits (6 and 15mm, n=7 each), 2) Mg (6mm, n=7; 15mm, n=8), 3) titanium (6mm only, n=7), or 4) isograft nerve controls (donor rats, 15mm, n=8). After sacrifice (6 weeks for short, 14 weeks for long gaps), the reconstructed nerve was excised, fixed and imaged by micro computed tomography (microCT) to determine extent of Mg degradation. Gastrocnemius muscles were removed and weighed. After imaging, nerves were halved and treated with either osmium to enhance contrast and imaged by microCT or paraffin embedded, sectioned and stained with H&E or immunostained for axons (anti-NF200).
Results: Mg degradation (seen via microCT) appeared accelerated (gaps at 6 weeks and almost no metal at 14 weeks). This was thought to be due to metal fatigue from processing. With short nerve gaps, there was no difference in muscle recovery or anti-NF200 staining between empty, titanium or Mg groups. Titanium filaments did not degrade, but this inert physical support also did not appear to improve regeneration characteristics (p>0.05). In long gap experiments, use of Mg microfilaments showed improvement over empty controls in terms of greater cross sectional area of total regenerating tissues (3.7 vs 2.4 mm2, p<0.001) and greater area of axonal (anti-NF200) staining (62000 vs 25000 pixels, p<0.05). Muscle regeneration was not improved with Mg or empty groups at 14 weeks, but was with isografts (p<0.001).
Conclusions: Mg microfilaments improved the histologic characteristics of nerve bud regeneration through conduits across long nerve gaps, but did not improve muscle recovery at 14 weeks. Further research will focus on decreasing Mg degradation and assessing the effects of Mg++ ions on nerve regeneration.
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