A Comprehensive Review on Bioprinted Graphene-Based Material (GBM)-Enhanced Scaffolds for Nerve Guidance Conduits

Abstract

Peripheral nerve injuries (PNIs) pose significant challenges to recovery, often resulting in impaired function and quality of life. To address these challenges, nerve guidance conduits (NGCs) are being developed as effective strategies to promote nerve regeneration by providing a supportive framework that guides axonal growth and facilitates reconnection of severed nerves. Among the materials being explored, graphene-based materials (GBMs) have emerged as promising candidates due to their unique properties. Their unique properties-such as high mechanical strength, excellent electrical conductivity, and favorable biocompatibility-make them ideal for applications in nerve repair. The integration of 3D printing technologies further enhances the development of GBM-based NGCs, enabling the creation of scaffolds with complex architectures and precise topographical cues that closely mimic the natural neural environment. This customization significantly increases the potential for successful nerve repair. This review offers a comprehensive overview of properties of GBMs, the principles of 3D printing, and key design strategies for 3D-printed NGCs. Additionally, it discusses future perspectives and research directions that could advance the application of 3D-printed GBMs in nerve regeneration therapies.

Keywords: 3D printing; graphene-based materials; nerve guidance conduits; tissue engineering.

Figure 1

Synthesis methods of PG, GO, and rGO [45].

Figure 2

Examples of different bioprinting techniques [114].

Figure 3

Schematic demonstration of inkjet printing methods: (A) Continuous inkjet printing: Liquid is dispersed into continuous droplets, with droplet designation controlled by electric charge and field. (B) Drop-on-demand (DOD) inkjet printing: Droplets are ejected selectively to form patterns. (B1) Thermal inkjet: Droplets are ejected by bubble formation through heating. (B2) Piezoelectric inkjet: Droplets are generated via vibration of a piezoelectric actuator. (B3) Electrostatic inkjet: Droplets are ejected by deforming a pressure plate. (C) Electrohydrodynamic jet printing: Droplets are produced using a high-voltage electric field [118].

Figure 4

Schematic demonstration of (a) SLA, (b) DLP, and (c) 2P-SL printing techniques [123].

Figure 5

Flow chart of 3D-printed PU/PEGGO for NGCs [142].

Figure 6

(a) Schematic illustration of GBM-based NGCs fabricated using a rolling tubular model with 50 μm microneedles. The green layers are PDA/RGD mixed layers, the purple layer is graphene and PCL mixed layer and the blue layer is a repetition of the graphene and PCL mixed layer [153]. (b) (A): optical images of GO/PCL NGCs; (B,C): SEM images showing the nanoporous structure of the GO/PCL NGCs; (D): TEM images showing the uniform distribution of GO nanoparticles in PCL scaffolds [154]. (c) Schematic illustration of the fabrication of multiscale filled NGCs: (i) MEW printing of PCL microfibers on a rotating mandrel; (ii) MEW printing of rGO/PCL microfibers; (iii) electrospinning of PCL/collagen nanofibers and removal from the mandrel to obtain an MH-NGC; (iv) MEW printing of a fibrous sheet comprising PCL microfibers (yellow) and rGO/PCL microfibers (red); (v) rolling the fibrous sheet; and (vi) inserting the densely packed fibrous sheet into the lumen of a multiscale hollow NGC to create an MF-NGC. (vii) Schematic of 3D-printed MF-NGCs: (vii) cross-sectional view of the MF-NGC and (viii) oblique-sectional view of the MF-NGC [155].

Figure 7

(a) Schematic of the dual-core EHD printing system. (b(i–iv)) Sequential images of dual-core jet formation during dual-core filament production. (c) Diagram of graphene-loaded dual-core fibers: (i) before and (ii) after the drug release process [156].

Figure 8

Schematic illustration of 3D polymeric grid-patterned scaffolds, decorated with a visible-light photocatalyst, serving as NGCs to enhance peripheral neural regeneration [165].

Figure 9

Schematic illustration of 3D-printed graphene-based interdigitated circuit activate MSCs differentiation [145].

Figure 10

(a) Illustration of dispersed liquid inks prior to extrusion. (b,c) SEM images of the fiber exterior and cross-section, respectively. (d) Example illustrating the measurement of flake orientation in an end-on cross-sectional view of the 3DG fiber. (e) Histogram of graphene flake orientations with respect to the horizontal. (f) SEM and optical (inset) images of 3D scaffolds printed with a 100 μm tip. (g) Uniformity of 3D scaffolds quantified by fiber thickness in a 40-layer construct printed with a 100 μm tip [172].