Chondroinductive Alginate-Based Hydrogels Having Graphene Oxide for 3D Printed Scaffold Fabrication

Abstract

Scaffolds based on bioconjugated hydrogels are attractive for tissue engineering because they can partly mimic human tissue characteristics. For example, they can further increase their bioactivity with cells. However, most of the hydrogels present problems related to their processability, consequently limiting their use in 3D printing to produce tailor-made scaffolds. The goal of this work is to develop bioconjugated hydrogel nanocomposite inks for 3D printed scaffold fabrication through a micro-extrusion process having improved both biocompatibility and processability. The hydrogel is based on a photocrosslinkable alginate bioconjugated with both gelatin and chondroitin sulfate in order to mimic the cartilage extracellular matrix, while the nanofiller is based on graphene oxide to enhance the printability and cell proliferation. Our results show that the incorporation of graphene oxide into the hydrogel inks considerably improved the shape fidelity and resolution of 3D printed scaffolds because of a faster viscosity recovery post extrusion of the ink. Moreover, the nanocomposite inks produce anisotropic threads after the 3D printing process because of the templating of the graphene oxide liquid crystal. The in vitro proliferation assay of human adipose tissue-derived mesenchymal stem cells (hADMSCs) shows that bioconjugated scaffolds present higher cell proliferation than pure alginate, with the nanocomposites presenting the highest values at long times. Live/Dead assay otherwise displays full viability of hADMSCs adhered on the different scaffolds at day 7. Notably, the scaffolds produced with nanocomposite hydrogel inks were able to guide the cell proliferation following the direction of the 3D printed threads. In addition, the bioconjugated alginate hydrogel matrix induced chondrogenic differentiation without exogenous pro-chondrogenesis factors as concluded from immunostaining after 28 days of culture. This high cytocompatibility and chondroinductive effect toward hADMSCs, together with the improved printability and anisotropic structures, makes these nanocomposite hydrogel inks a promising candidate for cartilage tissue engineering based on 3D printing.

Fabrication and characterization of mechanically competent 3D printed polycaprolactone-reduced graphene oxide scaffolds

“…In 3D printed scaffolds specifically, in addition to the structural and physicochemical properties of the composite materials, geometrical features such as pore size, pore area, and strand diameter play important roles 50,60 . While most studies have reported that incorporating the GFMs into scaffolds and structures improves their mechanical performance 51,[61][62][63][64][65] , a few studies have shown differing results in which the addition of rGO has had no effect or adverse effects on the mechanical performance of the constructs 35,66 . The variations in between studies and the mechanical enhancements observed in our 3D printed constructs, is likely due to variations in all the above-mentioned parameters as well as the differing geometrical features.…”

3D Printing of Cytocompatible Gelatin‐Cellulose‐Alginate Blend Hydrogels

“…Herein, three different natural polymers—gelatin, alginate, and cellulose—were combined to integrate their advantages for extrusion‐based 3D printing. A number of studies have been published about the combination of gelatin with other biopolymers, [ 22–25 ] however detailed reports on combining gelatin with two different biopolymers as a 3D printing ink formulation, and investigating individual roles of the components on physicochemical properties of the composite material, such as biodegradability, and crosslinking strategy, are rather limited. In these studies, gelatin‐alginate solutions are commonly blended with pretreated cellulose derivatives in the form of nanofibers, [ 26 ] crystals, [ 27–29 ] or with carboxymethyl end groups, [ 30 ] followed by the fabrication of biocomposite hydrogel via either casting method [ 27,29–31 ] or using a recently favored technique, 3D printing.…”

Facile synthesis of alginate‐based calcium tungstate composite: A thermally stable blue emitting phosphor

“…15 Olate-Moya et al presented the synthesis of novel nanocomposite hydrogels based on alginate and graphene oxide as inks for 3D printing scaffolds. 16 And Zhao et al prepared hydrophilic ZnO nanoparticles and CA composite for water purification, which realized the sterilization and removal of organic pollutants with improved performance. 17 In our previous work, after in situ synthesis along with freeze-drying steps, CA/nano-calcium borate composites, CA/reduced graphene oxide (rGO) composites, and CA/nano-silver phosphate hybrid material exhibited superior thermal stability than neat CA.…”

“…For instance, Shang et al reported nonflammable alginate nanocomposite aerogels prepared by a simple freeze‐drying and post‐crosslinking method, and the results indicated that the fabricated alginate aerogels exhibited a three‐dimensional (3D) network structure 15 . Olate‐Moya et al presented the synthesis of novel nanocomposite hydrogels based on alginate and graphene oxide as inks for 3D printing scaffolds 16 . And Zhao et al prepared hydrophilic ZnO nanoparticles and CA composite for water purification, which realized the sterilization and removal of organic pollutants with improved performance 17 .…”