Effect of sodium L-lactate on bioactive properties of chitosan-hydroxyapatite/polycaprolactone conduits for peripheral nerve tissue engineering

Biomaterials and synthetic polymers have been widely used to replicate the regenerative microenvironment of the peripheral nervous system. Chitosan-based conduits have shown promise in the regeneration of nerve injuries. However, to mimic the regenerative microenvironment, the scaffold structure should possess bioactive properties. This can be achieved by the incorporation of biomolecules (e.g., proteins, peptides) or trophic factors that should preferably be aligned and/or released with controlled kinetics to activate the process of positive axon chemotaxis. In this study, sodium L-lactate has been used to enhance the bioactive properties of chitosan-hydroxyapatite/polycaprolactone electrodeposits. Next, two methods have been developed to incorporate NGF-loaded microspheres - Method 1 involves entrapment and co-deposition of NGF-loaded microspheres, while Method 2 is based on absorption of NGF-loaded microspheres. The study shows that modification of chitosanhydroxyapatite/polycaprolactone conduits by sodium L-lactate significantly improves their bioactive, biological, and physicochemical properties. The obtained implants are cytocompatible, enhancing the neurite regeneration process by stimulating its elongation. The absorption of NGF-loaded microspheres into the conduit structure may be considered more favorable for the stimulation of axonal elongation compared to entrapment, as it allows for trophic factor dose-dependent controlled release. The developed conduits possess properties essential for the successful treatment of peripheral nerve discontinuities.