Biocompatibility and Angiogenic Effect of Chitosan/Graphene Oxide Hydrogel Scaffolds on EPCs

Abstract

Angiogenesis in the field of tissue engineering has attracted significant attention. Graphene oxide has become a promising nanomaterial in tissue engineering for its unique biochemical properties. Therefore, herein, a series of chitosan (CS)/graphene oxide (GO) hydrogel scaffolds were synthesized by crosslinking CS and GO at different concentrations (0.1, 0.5, and 1.0 wt.%) using genipin. Compared with the CS hydrogel scaffolds, the CS/GO hydrogel scaffolds have a better network structure and mechanical strength. Then, we used endothelial progenitor cells (EPCs) extracted from human umbilical cord blood and cocultured these EPCs with the as-prepared scaffolds. The scaffolds with 0.1 and 0.5 wt.%GO showed no considerable cytotoxicity, could promote the proliferation of EPCs and tube formation, and upregulated the expressions of CD34, VEGF, MMP9, and SDF-1 in EPCs compared to the case of the scaffold with 1.0 wt.%GO. This study shows that the addition of graphene oxide improves the structure of chitosan hydrogel and enhances the proliferation activity and angiogenic capacity of EPCs.

Biomedical applications of chitosan-graphene oxide nanocomposites

“…These composites exhibit performance which overcomes limitations observed by the individual components (i.e., poor mechanical performance and low biocompatibility, respectively). Recent studies have shown that the synergistic effect between CS and GO generates hybrids with not only improved thermal stability, mechanical and optical properties ( Chen et al., 2019 ; Cobos et al., 2017 ; Kumar and Koh, 2014 ; Zhang et al., 2018a ) but also excellent in vitro and in vivo biocompatibility ( López Tenorio et al., 2019 ; Valencia et al., 2021 ; Zhang et al., 2021 ), angiogenic and cell growth effect ( Zhang et al., 2018b , 2021 ), antimicrobial properties ( Grande et al., 2017 ; Khalil et al., 2020 ), electrical conductivity ( Jiang et al., 2019 ) and adsorption capacities ( Wu et al., 2020a ; Yu et al., 2017b ), etc. Therefore, nanocomposites containing CS and GO have been widely created for developing improved thermomechanical and antimicrobial properties of food packaging film ( Ahmed et al., 2017 ; Grande et al., 2017 ), conductive three-dimensional scaffolds, coating, and nanofiber for tissue engineering ( Arnaldi et al., 2020 ; Cao et al., 2017 ; Jiang et al., 2019 ; Karimi et al., 2019 ), nanoparticle and hydrogel with great loading capacity and releasing profile for drug delivery ( Wang et al., 2018a ; Zhao et al., 2017b ), antibacterial film and hydrogel patch for wound healing ( Najafabadi et al., 2020 ; Yang et al., 2019c ), nanofiber and film with high load carrying capacity and electrochemical properties for biosensor ( Fazial and Tan, 2021 ; Li et al., 2019 ), sponge and membrane with strong adsorption power for wastewater treatment ( Bandara et al., 2019 ; Qi et al., 2018 ), and so on .…”

Engineering Tissues of the Central Nervous System: Interfacing Conductive Biomaterials with Neural Stem/Progenitor Cells

“…[180,181,366] Multilayered, tubular structures have been typically made by either stacking multiple films or nanofiber mats that are then rolled together [337] or electrospinning layers directly onto a cylinder. [365,366] Qian et al created layered, tubular scaffolds in which the innermost layer consisted of polydopamine and arginylglycylaspartic acid (RGD), followed by two layers of a PCL/graphene film, and an outermost layer of polydopamine and RGD. [365] Polydopamine and RGD layers facilitated cell adhesion while PCL/graphene layers enabled local electrical activity.…”

“…Compared to 2D substrates, scaffolds with 3D geometries can better recapitulate the microenvironment surrounding a cell in CNS tissues. Conductive 3D scaffolds have been made using techniques that include layer-by-layer assembly, [364][365][366] often combined with electrospinning as with the conduits described above, [364,365] and 3D printing. [367][368][369] Stacking and annealing 2D, conductive layers have led to the production of relatively thick, 3D cell scaffolds.…”

“…Graphene nanoparticles or powders have been incorporated into hydrogels made from various biomaterials, including collagen I, [ 377 ] gelatin, [ 289 ] alginate, [ 378 ] agarose, [ 379 ] silk, [ 380 ] chitosan, [ 381 ] polysaccharides, [ 382,383 ] and polyacrylamide, [ 375 ] by suspending graphene within the hydrogel solution prior to crosslinking. In both physically and covalently crosslinked hydrogels, increasing concentrations of graphene have been found to correlate with increased mechanical modulus and worsening cytocompatibility.…”

“…[365,367] Similar guidance conduits have been explored for their ability to facilitate axon regeneration across spinal cord lesions and as carriers for transplanted NS/PCs that direct their maturation. [180,181,366] Multilayered, tubular structures have been typically made by either stacking multiple films or nanofiber mats that are then rolled together [337] or electrospinning layers directly onto a cylinder. [365,366] Qian et al created layered, tubular scaffolds in which the innermost layer consisted of polydopamine and arginylglycylaspartic acid (RGD), followed by two layers of a PCL/graphene film, and an outermost layer of polydopamine and RGD.…”