Composition-structure-property Relationships For Experimental Composite Nerve Guidance Conduits
Authors:   ,   Cork Institute of Technology, Zhang Xiaofang 
Published: September 2024

Many Nerve Guidance Conduits (NGCs) have been approved by the Food and Drug Administration (FDA) as an alternative to nerve autografting for guiding peripheral nerve regeneration. However these materials offer little therapeutic potential for favourable axon growth environment, and difficulty in balancing the mechanical properties and the degradation rate of the implanted material is also a contemporary challenge. This project involved the design of experimental composite NGCs comprising glass particles and Pluronic FI27 in the copolymer (poly(lactic-co-glycolic acid)) and examined the composition-structure-property relationships for such materials. Three glasses (0.5Si-(x) Na-0.2Ca-0.13Zn-(0.17-x) Ce) (0.0.04 > x > 0.14) were produced. Glasses were characterised using x-ray diffraction (XRD), Differential Thermal Analysis (DTA), network connectivity calculations, and <sup>29</sup>Si magic angle spinning nuclear magnetic resonance spectroscopy (MAS-NMR). The degradability (quantified Ca<sup>2+</sup> and Zn<sup>2+</sup> ion release) and the cytocompatibility of three glasses were investigated over 1, 3, 7, and 30 days incubation periods according to ISO 10993-14 and ISO 10993-5, respectively. The degradation profile indicated heterogeneous dissolution of glass networks. All three glasses indicated good biocompatibility. The PLGA/F127 conduits were synthesised with increments of FI27 from 0-5wt%, and the wet-state mechanical property of such conduits was tested in order to examine the effect of the additional FI27 on the mechanical property of the conduits. No significant difference was found between the different compositions. Based on Ca<sup>2+</sup> and Zn<sup>2+ </sup>release profiles and the cell variability results, the glass with the highest Na:Ce ratio was brought forward for the experimental design of thirteen PLGA/F 127-Glass NGCs (called CNGC) according to a Box-Behnken design. The effects of each factor on the responses (initial mechanical property and cell variability) were found out through response surface methodology (RSM) techniques and a desirable design was predicted via optimization technology. The wet-state mechanical properties and the cytocompatibility of six of the thirteen CNGCs were investigated over 1, 3, 7, and 28 day incubation periods. The results show a superior cytocompatibility when compared with the published literature for the clinically used nerve guidance conduit Neurolac®, and a comparable mechanical property was obtained for CNGC-I andCNGC-J. All the ions released from CNGC which contain the CNG glass (6 CNGCs) were examined over 1, 3, 7, and 28 day incubation periods. The Si<sup>4+</sup>, Na<sup>+</sup>, Ca<sup>2+</sup> Zn<sup>2+</sup> release from CNGCs in this study were ranged from 0.22 - 6.477ppm, 2.307 -3.277ppm, 40 -119ppm, and 45-51 ppm, respectively. The Ce<sup>3+</sup> concentrations were under the minimum detection limits of the ICP standard and instrument utilized for each CNGC. The C<sup>2+</sup> and ZnV release results indicated that all examined CNGC containing Zn and Ca may have potential therapeutic effect with respect to the peripheral nerve regeneration. In general, the results from the viability assay indicated that the experimental NGC showed comparable mechanical properties and cell viabilities when compared to the commercial control Neurolac®, demonstrating the equivalent or even enhanced in vitro compatibility of these CNGCs in relation to a current state of the art material. As such this project has resulted in the development a new approach to nerve repair and has new materials which show excellent potential as NGCs have been synthesized.