Reduced Graphene Oxide‐GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering

Abstract

Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cellular behavior. In this work, we engineered myocardial tissue constructs based on reduced graphene oxide (rGO)-incorporated gelatin methacrylyol (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhanced the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibited better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes showed stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial design to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro.

A conducting polymer with enhanced electronic stability applied in cardiac models

“…Conductive materials used in the fabrication of these scaffolds include conjugated polymers ( 26 , 43 , 44 ), carbon-based materials such as graphene/graphene oxide ( 45 , 46 ) and carbon nanotubes ( 47 – 49 ), and metallic nanoparticles or nanowires such as gold ( 50 ). Introducing conductivity in these scaffolds resulted in several benefits: enhanced electrical coupling ( 47 , 48 , 50 ), higher rates of spontaneous beatings of cardiomyocytes cultured on these scaffolds ( 46 ), and improved function of infarcted hearts ( 45 , 49 ). Having established that our patch sustains its electronic properties in vitro, we set out to investigate in the first instance whether its attachment to cardiac tissue will have any effect on the mechanical or electrophysiological function.…”

Advances in engineering hydrogels

“…Engineered skeletal muscles, when bound to bioprinted hydrogel frameworks, could also actuate and move the devices in defined patterns (13, 14). These bioactuators relying on cell traction forces may be remotely controlled by a variety of external stimuli such as electrical signals (95–97) and light (14, 94). To be suited for building robust bioactuators, hydrogels must be both bio-compatible and mechanically stable.…”

Recent advances in photo-crosslinkable hydrogels for biomedical applications

“…For cardiac tissue engineering, other materials such as reduced graphene oxide or carbon nanotubes were incorporated into GelMA hydrogel to increase its electrical conductivity for maturation of cardiomyocytes. Upon electrical stimulation, cardiomyocytes encapsulated in such hybrid hydrogels demonstrate a higher expression of cardiac markers and faster spontaneous beating than those encapsulated in the pristine GelMA hydrogels [87,88]. GelMA/black phosphorus hybrid hydrogel could also be a promising scaffold for such application [89].…”