3D-Printed Conductive Growth Factor-Eluting Nerve Guide Conduits for Peripheral Nerve Regeneration in Long Nerve Gap Injuries

Peripheral nerve injuries (PNI) present significant clinical challenges due to their complex nature and limited regenerative capacity. Current treatments, such as autografts and allografts, often face limitations including donor site morbidity and immune rejection. This thesis aims to address these challenges by developing advanced 3D printed nerve guide conduits (NGCs) that are capable of enhancing nerve regeneration in long-gap nerve

injuries. This research encompasses the design, fabrication, and evaluation of NGCs utilizing novel biomaterials and biofabrication techniques. The initial focus is on computational fluid dynamics (CFD) modeling to optimize drug-eluting NGC designs, ensuring efficient and sustained delivery of growth factors. Subsequently, a tri-layered NGC is developed using melt-electrowriting and extrusion-based 3D bioprinting. This conduit demonstrates mechanical robustness, biocompatibility, and supports neural stem cell viability and differentiation.

To further enhance the functionality of NGCs, a soft and conductive hydrogel is synthesized by incorporating choline-based ionic liquids (ILs) into gelatin methacrylate (GelMA). The resulting hydrogel exhibits improved electrical conductivity without compromising mechanical properties and biocompatibility. The integration of laponite nanoparticles into the GelMA/IL hydrogel significantly enhances printability and drug delivery, facilitating sustained release of therapeutic agents and supporting cell proliferation and differentiation. The thesis concludes with a discussion on the limitations of the current designs and materials, and provides an outlook on future research directions. Emphasis is placed on enhancing the nerve regeneration of NGC from various aspects (design, conductivity and drug delivery) and the future work should focus on transitioning to advanced in vivo tests to validate their clinical efficacy. Overall, this work presents a comprehensive approach to developing next-generation NGCs for improved peripheral nerve regeneration, potentially transforming treatment paradigms for PNI.