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

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 i sograft 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 de fect 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 anim als were harvested and histomorphologically analyzed. Multiple samples were collected and expressed as means +/- standard error. A two-sample t-test a nd Wilcoxon rank sum test was used to compare the variables. Significance l evel was set at alpha = 0.05. After Bonferroni correction for multiple test ing, a p value of less than or equal to 0.01 was considered statistically s ignificant. Throughout all time periods, the PLLA conduit remained structurally intact and demonstrated tissue incorporation and vascularization. There was no evi dence of conduit collapse or breakage with limb ambulation. Moreover. there was no evidence of conduit elongation at 8 months as previously observed w ith the 75:25 poly(DL-lactic-co-glycolic acid) (PLGA) conduits. The mean ab solute value of the sciatic functional index (SFI) demonstrated no group di fferences from isograft controls measured over the 8 months: except at 3 mo nths 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 3 months the number of axons/mm (2) and nerve fiber density was nor significantly different between the iso graft control and experimental groups in tither the midconduit/isograft or distal nerve. At 8 months the number of axons/mm(2) was significantly lower in the isograft compared to the midconduit experimental group (p = 0.006). The number of axons/mm(2) 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 aw are however that longer evaluation of polymer degradation is warrented. Fur ther studies on these individual nerve components are continuing, with the ultimate goal being the fabrication of a bioactive conduit that meets or ex ceeds the functional results of isografts.