Biomimetic Photocurable Three-Dimensional Printed Nerve Guidance Channels with Aligned Cryomatrix Lumen for Peripheral Nerve Regeneration

Abstract

Repair and regeneration of the critically injured peripheral nerves is one of the most challenging reconstructive surgeries. Currently available and FDA approved nerve guidance channels (NGCs) are suitable for small gap injuries, and their biological performance is inferior to that of autografts. Development of biomimetic NGCs with clinically relevant geometrical and biological characteristics such as topographical, biochemical and haptotactic cues could offer better regeneration of the long gap complex nerve injuries. Here, in this study, we present the development and preclinical analysis of a 3D printed aligned cryomatrix filled NGCs along with nerve growth factor (NGF) (aCG+NGF) for peripheral nerve regeneration. We demonstrated the application of these aCG+NGF NGCs in the enhanced and successful regeneration of a critically injured rat sciatic nerve in comparison to random cryogel filled NGCs, multichannel, and clinically preferred hollow conduits as well as gold standard autografts. Our results indicated viz-a-viz similar effect of aCG+NGF NGCs to that of autografts, and not only enhanced the overall regenerated nerve physiology, but could also mimic the cellular aspects of regeneration. This study emphasizes the paradigm that these biomimetic 3D printed NGCs will lead to a better functional regenerative outcome under clinical settings.

Characterizing Cross‐Linking Within Polymeric Biomaterials in the SEM by Secondary Electron Hyperspectral Imaging

“…The photocurable capability of PGS-M enhances the existing strengths of PGS by allowing the material to be cross-linked at lower temperatures and pressures. [15,16] Further validation is required to confirm this relationship but PGS-M is generating much interest as a biomaterial. [15] The ease with which PGS-M can be synthesized together with the adaptability of its physical properties and suitability for use with different cell types, makes PGS-M an attractive candidate for an extensively deployed biomaterial.…”

Additive Manufacturing of Nerve Guidance Conduits for Regeneration of Injured Peripheral Nerves

“…However, compared with natural biological materials, their biocompatibility is poor. Several synthetic materials, such as PCL (Singh et al, 2018), poly(lactic acid-co-glycolic acid) (PLGA) (Radulescu et al, 2007), poly(ethylene glycol) (PEG) (Christopher et al, 2015;Evangelista et al, 2015), poly(glycerol sebacate) (PGS) (Dharaminder et al, 2018), polypyrrole (PPy) (Weng et al, 2012) and carbon nanotubes (CNTs) (Lee et al, 2018a) have been used alone or in combination with natural polymers for 3D-printed NGCs.…”

Three‐dimensional cryogels for biomedical applications

“…Traditional NGCs are FDA‐approved conduit guides for the regeneration of injured nerve over small gaps, but these have been found to be clinically inferior compared to nerve autografts, as well nonsuitable for the regeneration of long‐gap complex nerve injuries. However, Singh et al () described the augmented regenerative potentiation of 3D‐printed cryogel‐filled NGCs for enhanced and successful regeneration of critically‐injured rat sciatic nerves. Their results indicated that guided‐regeneration, via 3D‐printed cryogel‐filled NGCs, led to a comparable regain of rat sciatic nerve physiology and cellular function compared to the gold‐standard autografts (Singh et al, ).…”

“…However, Singh et al () described the augmented regenerative potentiation of 3D‐printed cryogel‐filled NGCs for enhanced and successful regeneration of critically‐injured rat sciatic nerves. Their results indicated that guided‐regeneration, via 3D‐printed cryogel‐filled NGCs, led to a comparable regain of rat sciatic nerve physiology and cellular function compared to the gold‐standard autografts (Singh et al, ).…”