Biofabrication of nerve guidance conduits

Abstract

The regeneration and functional recovery of peripheral nervous system (PNS) after injury is highly variable often leading to persistence of motor and sensorial deficits. Nerve guidance channels (NGCs) biocompatible and biodegradable with capacity of neurotrophic factors release, could have therapeutic potential in the PNS severe traumatic injuries. New technologies such as three-dimensional (3D) bioprinting allow the biofabrication of nervous constructs that can be functionalized with neurotrophic factors (FNs) to optimize the results. 3D bioprinting shows advantages such as excellent cost-benefit, rapid repeatability and scalability. In this study, 3D bioprinting is going to be used to develop NGCs from polycaprolactone (PCL) and gelatin methacrylate (GelMA) bioink, incorporated with fibroblast growth factor-2 (FGF-2) (PCL/GelMA/FGF-2 bioink), which can allow local and sustained FGF-2 release, a crucial factor for nervous system repair and restoration. In vitro, the NGCs ultraestructure, FGF-2 release and degradability are going to be analyzed. The interaction of mesenchymal stem cells (MSCs) on NGC surface and NFs gene expression are going to evaluate. In vivo, functional and electrophysiological recovery after sciatic nerve injury in rats and repair using NGC are going to be analyzed. Finally, the morphometry and reactivity and proliferation of Schwann cells (CS) analysis in the regenerated nerve are going to be performed. The proposed biofabrication, could accelerate and optimize nerve regeneration by local and sustained FGF-2 in the injured microenvironment, being an alternative to the nerve autograft technique. The results aim at a translational potential for the treatment of SNP injuries. (AU)