Structural Design Strategies of Nerve Guidance Conduits for Improved Axonal Direction and Recovery: A Review on Current Approaches, Challenges and Future Perspectives

Introduction: Autologous nerve grafts (ANGs) are the standard for nerve reconstruction, but their limitations have driven research into the development of artificial nerve grafts, differently known as nerve guidance conduits (NGCs). Axonal misdirection is one of the greatest obstacles to ensuring successful nerve repair, whether relying on ANGs or NGCs. This paper reviews the NGC structural designing strategies and assesses their potential to influence axonal direction, exploring the key challenges and future perspectives.

Methods: The available medical literature in English was reviewed using PubMed, ScienceDirect, OpenMD, Cochrane Library, and Google Scholar databases. The importance of reducing axonal misdirection to achieve optimal outcomes was analyzed. Reported strategies for NGC structural design were described, with a focus on their impact on axonal misdirection. Key challenges and future perspectives are discussed.

Results: Axonal misdirection, stemming from dispersive growth and complex intraneural branching, can result in terminated growth, mismatched synapsing, or incorrect reinnervation, affecting outcomes even in favorable cases. Basic single-hollow NGCs reduce lateral deviation but often lack directionality, while porous, grooved, and bio-active variants improve guidance in smaller gaps. Multichannel and nanofiber/sponge-filled NGCs offer better structure for longer gaps, though they’re limited in clinical use due to fabrication challenges. Future strategies may include 3D-printed, patient-specific conduits tailored to individual nerve topography using insights from MR neurography, intraoperative 3D scans, and machine learning predictions to address axonal misdirection more effectively.

Conclusion : The significance of this study lies in addressing a critical limitation in current nerve repair techniques, by evaluating structural modifications of iNGCs that could potentially improve outcomes over traditional ANGs. These insights lay a groundwork for future innovations, such as 3D-printed, patient-specific conduits, which could transform the approach to nerve repair by offering customized, anatomically precise solutions.