Multifunctional hyaluronic acid/graphite nanoplatelet hydrogels as tools for spinal cord regeneration

Abstract

Spinal cord injury (SCI) is a condition that interrupts neural electrical conduction, resulting in significant motor and sensory dysfunction. Current treatments remain inadequate for fully restoring neuronal activity, highlighting the urgent need for advanced neurodegenerative materials to reconnect disrupted nerve pathways and recover neural connectivity and function. Herein, conductive and adhesive hydrogel composites based on hyaluronic acid (HA) filled with exfoliated graphite nanoplatelets (EG) or pyrrolidine-functionalized EG (f-EG) are developed. Adhesive catechol-conjugated HA (HA-Cat) is obtained by a reaction of HA-aldehyde with dopamine and subsequent reduction. Then, hydrogel composites (HA-C) are produced using sodium periodate as an oxidative agent. The incorporation of 50% f-EG substantially increased the electrical conductivity of HA-C, supporting efficient electrical signal transmission, which is essential for nerve repair. The hydrogels exhibited mechanical properties suitable for neural tissue regeneration along with adhesive and self-healing capabilities that promote integration at the injury site. Moreover, undifferentiated SH-SY5Y cells cultured on HA-C reinforced with EG or f-EG showed enhanced cell attachment and viability after electrical stimulation. The results demonstrate that the developed hydrogel composites are promising biomaterials for SCI repair by filling the injury site, bridging the damaged neural pathway, and mimicking the bioelectrical properties of the spinal cord’s bioelectrical properties.