DEVELOPMENT AND TESTING OF CHITOSAN-BASED SCAFFOLDS FUNCTIONALIZED WITH PHOSPHODIESTERASE INHIBITORS FOR PERIPHERAL NERVE REGENERATION

Peripheral nerve injuries pose a significant clinical challenge, with limited recovery in complex cases. Biocompatible scaffolds incorporating topographical and biochemical cues offer a promising strategy to enhance nerve regeneration. This thesis developed chitosan-based microstructured membranes functionalized with Sildenafil, a phosphodiesterase inhibitor (PDEI) known to support neuronal and glial functions. Initially, the effects of Sildenafil and Rolipram on Schwann cells (SCs) were assessed. While statistical significance was not achieved, Sildenafil showed a positive trend in promoting SC migration without compromising viability. Thus, Sildenafil was incorporated into chitosan-glycerol membranes fabricated via solvent casting on microstructured molds. The resulting membranes maintained stability, microstructure, and biocompatibility. Drug release studies confirmed Sildenafil's controlled release at micromolar concentrations suitable for SCs. Gene expression analysis (qPCR) further validated its bioactivity. Overall, these findings demonstrate the potential of Sildenafil-functionalized chitosan membranes as a novel strategy for peripheral nerve regeneration.