Preparation and characterization of angled dual- and multi-branched nerve guidance conduits

Branched nerve guidance conduit (NGC) provides a promising alternative to autografts for the effective treatment of severe peripheral nerve injuries. Despite this, the impact of branched architecture on nerve regeneration remains unclear, particularly concerning branch angle and number in multi-branched NGCs. In this study, we investigated the effects of branch angle and number on nerve regeneration by preparing and characterizing multi-angled and multi-branched NGCs. We designed and fabricated dual-branched NGCs (DBNs) with various branch angles and multi-branched NGCs (MBNs) through a digital light processing (DLP) printing process. When branched NGCs were implanted to bridge the linear sciatic nerve gap, nerve dual branches with acute (45°), right (90°), or obtuse (120°) branch angles were formed in DBNs, while nerve multi-branches were generated in MBNs. The regenerated nerves in DBNs with various angles exhibited comparable electrophysiological conduction and histological morphologies, indicating that the branch angle of dual-branched NGCs may not affect nerve branch regeneration. In contrast, the diameter of the regenerated nerve branches in MBNs decreased with increasing distance from the scaffold center, highlighting the potential significance of branch number in the design of branched NGCs. This study contributes valuable insights for designing, preparing, and applying branched NGCs, offering potential assistance in advancing nerve regeneration strategies.