Composition-property relationships for an experimental composite nerve guidance conduit: evaluating cytotoxicity and initial tensile strength

Abstract

The objective of this work was to examine the main (individual), combined (interaction) and second-order (quadratic) effects of: (i) poly(D,L-lactide-co-glycolide) (PLGA), (ii) F127, and (iii) a zinc-silicate based bioactive glass, on the cytotoxicity and ultimate tensile strength of an experimental nerve guidance conduit (NGC). The experimental plan was carried out according to a Box-Behnken design matrix. The effects of each compositional factor were quantified using response surface methodology (RSM) techniques. Linear and quadratic polynomial equations were developed to examine cytotoxicity (after incubation at 3, 7 and 28 days) and initial ultimate tensile strength (UTS(0)). Multiple regression analyses showed that the developed models yielded a good prediction for each response examined. It was observed that the beneficial effects of PLGA and bioactive glass on controlling cytotoxicity appeared greater than that of F127. Furthermore, the experimental conduits (with the exception of CNGC-I and CNGC-K) generally showed superior cytocompatibility when compared with the comparable literature for the clinically used nerve guidance conduit Neurolac(®). In this investigation, optimal compositions for cell viability were obtained for the following composition: PLGA = 18.89 wt%/F127 = 0.52 wt%/glass = 12.71 wt%. The optimization of composition with respect to ultimate tensile strength was also established (desired UTS(0) being based on the properties of the control device Neurolac(®) whose UTS is c.20 MPa). The desired UTS(0) of ≤ 20 MPa was found for the composition: PLGA = 18.63 wt%/F127 = 0.77 wt%/glass = 5.54 wt%. A UTS(0) ≤ 30 MPa was recorded for the composition: PLGA = 18.34 wt%/F127 = 0.62 wt%/glass = 9.83 wt%, such tensile strengths are comparable to, reported values for Neurolac(®). Examination of the composition-property relationships with respect to combining cell viability and UTS(0) indicated preferred compositions in the range 17.97-19.90 wt% PLGA, 0.16-1.13 wt% F127 and between 5.54 and ≤ 20 wt% glass. This research demonstrates the value of a design of experiments approach for the design of novel nerve guidance conduits, and shows that the materials examined may have potential for the repair of peripheral nerve discontinuities.