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RESEARCH ARTICLE

Graphene Oxide-Embedded Extracellular Matrix-

Derived Hydrogel as a Multiresponsive Platform for 3D

Bioprinting Applications

Laura Rueda-Gensini, Julian A. Serna, Javier Cifuentes, Juan C. Cruz*, Carolina Muñoz-Camargo*

Department of Biomedical Engineering, Universidad de Los Andes, Bogotá, 11171, Colombia

Abstract: Decellularized extracellular matrices (dECMs) have shown enormous potential for the biofabrication of tissues due
to their biomimetic properties that promote enhanced cellular interaction and tissue regeneration. However, biofabrication
schemes requiring electrostimulation pose an additional constraint due to the insulating properties of natural materials. Here, we
propose a methacryloyl-modified decellularized small intestine submucosa (SISMA) hydrogel, embedded with graphene oxide
(GO) nanosheets, for extrusion-based 3D bioprinting applications that require electrostimulation. Methacryloyl biochemical
modification is performed to enhance the mechanical stability of dECM constructs by mediating photo-crosslinking reactions,
and a multistep fabrication scheme is proposed to harness the bioactive and hydrophilic properties of GO and electroconductive
properties of reduced GO. For this, GO was initially dispersed in SISMA hydrogels by exploiting its hydrophilicity and protein
adsorption capabilities, and in situ reduction was subsequently performed to confer electroconductive abilities. SISMA-GO
composite hydrogels were successfully prepared with enhanced structural characteristics, as shown by the higher crosslinking
degree and increased elastic response upon blue-light exposure. Moreover, GO was homogeneously dispersed without affecting
photocrosslinking reactions and hydrogel shear-thinning properties. Human adipose-derived mesenchymal stem cells were
successfully bioprinted in SISMA-GO with high cell viability after 1 week and in situ reduction of GO during this period
enhanced the electrical conductivity of these nanostructures. This work demonstrates the potential of SISMA-GO bioinks as
bioactive and electroconductive scaffolds for electrostimulation applications in tissue engineering and regenerative medicine.

Keywords: Extracellular matrix bioink; Graphene oxide; Reduced graphene oxide; Electroconductive hydrogel;
Photocrosslinking
*Correspondence to: Juan C. Cruz, Biomedical Engineering Department, Universidad de Los Andes, Bogotá, 11171, Colombia;
jc.cruz@uniandes.edu.co; Carolina Muñoz-Camargo, Department of Biomedical Engineering, Universidad de Los Andes, Bogotá, 11171,
Colombia; c.munoz2016@uniandes.edu.co
Received: March 12, 2021; Accepted: April 20, 2021; Published Online: May 11, 2021
Citation: Rueda-Gensini L, Serna JA, Cifuentes J, et al., 2021, Graphene Oxide-Embedded Extracellular Matrix-Derived Hydrogel
as a Multiresponsive Platform for 3D Bioprinting Applications. Int J Bioprint, 7(3):353. http://doi.org/10.18063/ijb.v7i3.353

1. Introduction proteins present in dECMs such as glycoproteins,
proteoglycans, and bound growth factors mediate
Decellularized extracellular matrices (dECMs) have morphological organization and physiological function [3]
gained significant attention over the past few decades as while glycosaminoglycans (GAGs) provide an extremely
biomaterials for tissue engineering due to their promising
potential as biomimetic scaffolds [1,2] . Composition-wise, hydrophilic environment essential for withstanding high
[4]
dECMs hold a complex of structural proteins such as compressive forces . Although ECM composition varies
collagen, laminin, elastin, and fibronectin, which in native depending on tissue function, its overall structure is similar
tissues grant adequate mechanical rigidity and structural for all tissues and, therefore, dECM hydrogels closely mimic
stability for cellular growth, migration, and proliferation, the native cellular environment. Moreover, several studies
and provide attachment sites for cell adhesion . Additional have revealed that the presence and cumulative action
[1]
© 2021 Rueda-Gensini, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.
org/ licenses/by/4.0/), permitting distribution and reproduction in any medium, provided the original work is cited.
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