Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration

G. R.D. Evans, K. Brandt, A. D. Niederbichler, P. Chauvin, S. Hermann, M. Bogle, L. Otta, B. Wang, C. W. Patrick

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

It was the purpose of this study to evaluate the clinical long-term effects of PLLA degradation in vivo on nerve regeneration in the rat sciatic nerve model. Thirty-one Sprague Dawley rats were utilized. Two groups of animals were selected. The control group of 10 animals received a 12 mm reversed isograft into the right sciatic nerve from 5 donor animals. The experimental group (n = 21) received a 12 mm empty PLLA conduits placed into a 12 mm defect in the right sciatic nerve. The left leg served as an internal control. Walking track analysis was performed monthly through 8 months. At the end of 4 and 8 months, animals in the control isograft and experimental group had the medial and lateral gastrocnemius muscles harvested and weighed for comparison. The midconduit/isograft and the distal nerve in these same animals were harvested and histomorphologically analyzed. Multiple samples were collected and expressed as means ± standard error. A two-sample t-test and Wilcoxon rank sum test was used to compare the variables. Significance level was set at α = 0.05. After Bonferroni correction for multiple testing, a p value of ≤ 0.01 was considered statistically significant. Throughout all time periods, the PLLA conduit remained structurally intact and demonstrated tissue incorporation and vascularization. There was no evidence of conduit collapse or breakage with limb ambulation. Moreover, there was no evidence of conduit elongation at 8 months as previously observed with the 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) conduits. The mean absolute value of the sciatic functional index (SFI) demonstrated no group differences from isograft controls measured over the 8 months except at 3 months where the isograft values were higher (p = 0.0379) and at 7 months were the isograft group was significantly lower (p = 0.0115). At 4 and 8 months, the weight of the gastrocnemius muscles of the experimental group was not significantly different from isografts. At 4 months the number of axons/mm2 and nerve fiber density was not significantly different between the isograft control and experimental groups in either the midconduit/isograft or distal nerve. At 8 months the number of axons/mm2 was significantly lower in the isograft compared to the midconduit experimental group (p = 0.006). The number of axons/mm2 in the distal nerve and the nerve fiber density in the midconduit and distal nerve were not significantly different between the two groups. The study confirmed our initial hypothesis that PLLA conduits are a viable scaffold for clinical long-term nerve gap replacement. We are critically aware however that longer evaluation of polymer degradation is warrented. Further studies on these individual nerve components are continuing, with the ultimate goal being the fabrication of a bioactive conduit that meets or exceeds the functional results of isografts.

Original languageEnglish
Pages (from-to)869-878
Number of pages10
JournalJournal of Biomaterials Science, Polymer Edition
Volume11
Issue number8
DOIs
StatePublished - Jan 1 2000

Keywords

  • Long-term evaluation
  • Peripheral nerve regeneration
  • Poly(L-lactic acid) porous conduits

Fingerprint

Dive into the research topics of 'Clinical long-term in vivo evaluation of poly(L-lactic acid) porous conduits for peripheral nerve regeneration'. Together they form a unique fingerprint.

Cite this