Synthetic conduits efficacy in neural repair: a comparative study of dip-coated polycaprolactone and electrospun polycaprolactone/ polyurethane conduits.

Abstract

Peripheral nerve injuries represent the most common type of nervous system injuries, resulting in 5 million injuries per year. Current gold standard, autografts, still carry several limitations, including the inappropriate type, size, and function matches in grafted nerves, lack of autologous donor sites, neuroma formation, and secondary surgery incisions. Polymeric nerve conduits, also known as nerve guides, can help overcome the aforementioned issues that limit nerve recovery and regeneration by reducing tissue fibrosis, misdirection of regenerating axons, and the inability to maintain long- distance axonal growth. Polymer-based double-walled microspheres (DWMS) are designed to locally and in a sustainable fashion deliver bioactive agents. Lysozyme is a natural antimicrobial protein that shares similar physical and chemical properties to glial cell line-derived neurotrophic factor (GDNF), making it an ideal surrogate molecule to evaluate the release kinetics of encapsulated bioagent from polymeric biodegradable microspheres embedded in Polycaprolactone and Polycaprolactone/Polyurethane blend nerve conduits.
Approach: Lysozyme was encapsulated in poly(lactic-co-glycolic acid)/poly(L-lactide) (PLGA/PLLA) double-walled microspheres fabricated through a modified water-oil-water emulsion solvent evaporation method. Lysozyme-loaded DWMS were further embedded in PCL and PCL-PU based nerve guides constructed via polymer dip-coating and electrospinning method respectively. Lysozyme DWMS and nerve guides were imaged using scanning electron microscopy (SEM). Released lysozyme concentration was determined by using a colorimetric micro-BCA protein assay and spectrophotometric quantitation. Tensile and suture pull-out tests were utilized to evaluate the mechanical properties of both dip-coated and electrospun nerve guides, embedded and free of lysozyme DWMS.
Main Results: The study revealed significant distinctions in the lysozyme release profiles, and mechanical properties of the manufactured polymer nerve guides. Both PCL dip-coated and PCL/PU electrospun DWMS-embedded nerve guides revealed biphasic protein release profiles. PCL/PU electrospun and PCL dip-coated nerve guides released 16% and 29% of the total protein concentration within 72 hours, plateauing at week 16 and week 8, respectively. SEM analysis of the nerve guides confirmed the homogeneity and integrity of the polymer nerve guides' structures. The electrospun guides were found to be more flexible with a higher extension under stress bending, while the dip-coated PCL nerve guides displayed more rigid behavior.
Significance: This study provides useful insights on how to optimize nerve guide design and fabrication to enhance recovery progress of peripheral nerve injuries.&#xD.