Nerve Guidance Conduits with Hierarchical Anisotropic Architecture for Peripheral Nerve Regeneration

Abstract

Nerve guidance conduits with multifunctional features could offer microenvironments for improved nerve regeneration and functional recovery. However, the challenge remains to optimize multiple cues in nerve conduit systems due to the interplay of these factors during fabrication. Here, a modular assembly for the fabrication of nerve conduits is utilized to address the goal of incorporating multifunctional guidance cues for nerve regeneration. Silk-based hollow conduits with suitable size and mechanical properties, along with silk nanofiber fillers with tunable hierarchical anisotropic architectures and microporous structures, are developed and assembled into conduits. These conduits supported improves nerve regeneration in terms of cell proliferation (Schwann and PC12 cells) and growth factor secretion (BDNF, brain-derived neurotrophic factor) in vitro, and the in vivo repair and functional recovery of rat sciatic nerve defects. Nerve regeneration using these new conduit designs is comparable to autografts, providing a path towards future clinical impact.

Anisotropic silk nanofiber layers as regulators of angiogenesis for optimized bone regeneration

“…The SF nanofibers were assembled through the concentration-dilution-thermal incubation process [ 30 ]. The SF molecules were self-assembled into metastable particles with the size of 100 ​nm after being concentrated to above 20% slowly at 60 ​°C for about 72 ​h.…”

“…The SF/HA-DFO-R composite scaffolds were immersed in SFN solution (0.5 ​wt%) for above 30 ​min to make sure that all the pores inside the scaffolds were occupied by the SFN solution. Then the SFN solution and the immersed scaffolds were treated under electric field with voltage of 50 ​V for 5, 10, 15 ​min to induce the SFN migration, forming SFN hydrogel layers with different thickness on the pore surface inside the scaffolds [ 29 , 30 ]. The treated scaffolds with SFN hydrogel layers were lyophilized for 72 ​h to obtain the final scaffolds with SFN layers.…”

“…The seeded BMSCs (5 ​× ​10 5 ​cells per well) were cultured in osteogenic differentiation medium (89% low glucose-DMEM, 10% FBS, 1% streptomycin-penicillin, 10 ​nM dexamethasone, 0.05 ​mM ascorbic acid-2-phosphate, and 10 ​mM sodium-β-glycerophosphate) for 3, 7, 14 and 21 days, respectively. According to the method mentioned above [ 29 , 30 ], the total proteins were extracted from the scaffolds for further tests.…”

“…Both in vitro and in vivo studies revealed that the DFO sustained release features determined angiogenesis, but did not fully control angiogenesis in a dynamic fashion matched with natural bone healing process. Anisotropic silk hydrogels derived from SFN solutions under electric fields directionally aligned the components on the positive electrode [ [28] , [29] , [30] ]. This study suggested that nanofiber layers with control of thickness could be prepared by adjusting the experimental time, followed by covering the surface of DFO-laden composite scaffolds, as a route to tune the release behavior of DFO.…”

Cortical‐Folding‐Inspired Multifunctional Reduced Graphene Oxide Microarchitecture Arrays on Curved Substrates

“…Controllable fabrication of hierarchical microarchitectures is of great significance for applications as diverse as soft actuators, [1,2] stretchable electronics, [3,4] cell culture, [5] water harvesting, [6,7] and microdroplet manipulation. [8,9] Although lithography and 3D printing techniques have been widely used to fabricate microarchitectures across multiple length scales, [10][11][12] it is still challenging to realize large-area fabrication of hierarchical microarchitecture arrays on curved substrates.…”