Development of Carbon Nanotubes-based Hydrogels for Nerve Tissue Regeneration

Nerve trauma often results in severe sensory and motor function loss due to axonal damage and demyelination. Current strategies aim to prevent neuromas formation and support guided nerve regeneration. Hydrogels, owing to their biomimetic properties, offer a promising platform for such applications.

The thesis introduces three novel hydrogel types: PVA/CNT hydrogels using dynamic low kinetic crosslinking (PBCLC),  phase inversion method (PIM), and swelling-resistant Chitosan hydrogels. These materials successfully incorporate high concentrations of multi-walled CNTs (up to 75% w/w) without compromising their structural integrity or elasticity, allowing for tunable properties that better mimic natural nerve tissue. Neuroblastoma SH-SY5Y cell growth and maturation were studied with the hydrogels, which highlighted various structural and mechanical cues for optimum cell coverage. To this end, the effect of CNTs dominated with PIM hydrogels showing highest cell coverage with increasing CNT content, whereas the effect of young’s modulus (YM) dominated in PBCLC hydrogels showing preference to higher YM regardless of CNT concentration. By porogen leaching method, the porosity of the hydrogels was controlled to 100-250 µm, through which cells showed increased cell coverage up to 80% and expression of neuronal maturity marker. Furthermore, SH-SY5Y cells occupied the hydrogels reshaping its interior structure and giving raise to the notion of cell- mediated matrix remodeling in a synthetic material previously seen on in ECM and ECM-derived materials. The study highlights how multiple cues play role in cell coverage and growth with a possibility that one cue could dominate the other while also highlighting guidelines for their analysis and effects. As a proof of concept, PIM hydrogels were used as nerve guidance conduit in the sciatic nerve. They were shown to have a clear effect in accelerating the onset of the regeneration process compared to control PIM hydrogels while allowing cell infiltration and axonal expansion paving the way towards clinical application of CNT for nerve tissue regeneration.