Electrically conductive and photocurable MXene-modulated hydrogel conduits for peripheral nerve regeneration: In vitro and in vivo studies

Electroconductive biomaterials, as advanced nerve guidance conduits (NGCs), have shown great promise to accelerate the rate of peripheral nerve repair and regeneration (PNR) but remain among the greatest challenges in regenerative medicine because of frail recovery. Herein, we introduce injectable nanocomposite nerve conduits based on gelatin methacrylate (GelMa) and MXene nanosheets (MX) for PNR. Microstructural studies determine that the addition of MX increases the mean pore size of GelMa NH from 5.8 ± 1.2 μm to 8.4 ± 1.6 μm for the hydrogel containing 0.25 mg/mL MX, for example, leading to higher swelling and degradation rates. The highest electrical conductivity (~910 μS/cm) is attained for the GelMa-based nanocomposite composed MX with the concentration of 0.125 mg/mL, for the reason that at higher concentrations, agglomeration of the MXs happens. In vitro investigations, including metabolic activity and live-dead assessments by PC12 cells, reveal the biocompatibility of developed nanocomposite hydrogels (NHs) containing different concentrations of MX nanosheets in the range of 0.025-0.25 mg/mL. Implantation of GelMa-MX conduits in a rat model of peripheral nerve injury (PNI) leads to the impressive recovery of the injured sciatic nerve’s sensory, motor, and sensory- motor function. Electrophysiological analysis also indicates a significant increase in compound muscle action potential and nerve conduction velocity with a decrease in terminal latency in animals implanted with GelMa- MX conduits compared to control groups (animals implanted with GelMa and animals without implantation). Moreover, histological analysis exhibits a notable absence of fibrousconnective tissue in the regenerated nerve fibers with a substantial increase in more organized myelinated axons. Our results demonstrate that GelMa-MX conduits promote regeneration of the injured sciatic nerve and could be promising for peripheral nerve tissue engineering.