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

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 alpha = 0.05. After Bonferroni correction for multiple testing, a p value of < or = 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.

In vitro and in vivo evaluation of a biodegradable chitosan–PLA composite peripheral nerve guide conduit material

“…The biodegradable conduit materials are categorized into two main groups: biological natural polymers (e.g., collagen, 18,19 gelatin, 20 and chitosan 7,8,21 ) and artificial synthetic materials (e.g., PGA 22 and PLA [12][13][14] ). Synthetic materials have such problems as inflammatory response from their degradation products in vivo, and lack of biological recognition.…”

“…However, it can be degraded in vivo into lactic acid, which influences cellular vitality negatively. 11,12 Although, along or with other materials, PLA and chitosan have been proposed as possible nerve conduit material, 13,14 the influence of chitosan-PLA composite nerve conduit on nerve regeneration has not yet been established. In this study, a small quantity of PLA was mixed with chitosan to enhance the mechanical strength and the elasticity of the material.…”

Nerve regeneration with the use of a poly(l-lactide-co-glycolic acid)-coated collagen tube filled with collagen gel

“…In this study, a collagen tube was coated with poly(l-lactide-co-glycolic acid) (PLGA) to enhance its structural integrity and elasticity. Although PLGA has been proposed as a nerve conduit material (Evans et al, 2000;Bryan et al, 2003;Bini et al, 2004), the influence of a collagen/ PLGA composite on nerve regeneration has not been established.…”

Synthesis and properties of caprolactone and ethylene glycol copolymers for neural regeneration

“…Polyesters like poly lactic acid (PLLA), poly glycolic acid (PGA) and their copolymers poly(lactic-co-glycolic acid) (PLGA) were one of the first polymers used because of their biodegradability through hydrolytic mechanisms, availability, and their ease of processing [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Hadlock et al [25] made a PLLA foam conduit materials seeded with Schwann cells to promote guide regeneration in the peripheral nerve.…”