Figure 5.

Due to the incapacity of hollow NGCs to bridge larger nerve gaps, various filler materials and designs have been developed to enhance the performance of NGCs. (A) The initial strategy consisted of simple hollow NGCs; When considering luminal fillers, experiments suggested that the regenerating axons prefer aligned features rather than random orientation. Therefore, many of the approaches focus on obtaining an anisotropic topography. With this strategy in mind, many types of luminal matrices are considered (B) Micro- or nano- filaments resembling the structure of endoneurial tubes; (C) Micro/nano groove-patterns; (D) Magnetically aligned fibrils or cells; (E) Micro-channel filling; (F) Unidirectionally freeze-dried; (G) Another strategy consist in inserting permissive hydrogels as luminal fillers, being a soft support to regenerative axons; and (H) One branch of PNR research also focuses on the controlled delivery of growth factors. That can be achieved, for instance, using crescent gradients of growth factors from the proximal to the distal sites, acting as a biochemical cue and attracting regenerating neurons to reach the final target.