Current in vivo and in vitro models fail to accurately recapitulate the human heart microenvironment for biomedical applications. This study explores the use of cardiac spheroids (CSs) to biofabricate advanced in vitro models of the human heart. CSs were created from human cardiac myocytes, fibroblasts and endothelial cells (ECs), mixed within optimal alginate/gelatin hydrogels and then bioprinted on a microelectrode plate for drug testing. Bioprinted CSs maintained their structure and viability for at least 30 d after printing. Vascular endothelial growth factor (VEGF) promoted EC branching from CSs within hydrogels. Alginate/gelatin-based hydrogels enabled spheroids fusion, which was further facilitated by addition of VEGF. Bioprinted CSs contracted spontaneously and under stimulation, allowing to record contractile and electrical signals on the microelectrode plates for industrial applications. Taken together, our findings indicate that bioprinted CSs can be used to biofabricate human heart tissues for long term in vitro testing. This has the potential to be used to study biochemical, physiological and pharmacological features of human heart tissue.

Functionalized poly(ethylene dioxythiophene) (f-PEDOT) was copolymerized with two vinyl monomers of different hydrophilicity, acrylic acid and hydroxyethyl methacrylate, to produce electroconductive hydrogels with a range of physical and electronic properties. These hydrogels not only possessed tailored physical properties, such as swelling ratios and mechanical properties, but also displayed electroactivity dependent on the chemical composition of the network. Raman spectroscopy indicated that the functional PEDOT in the hydrogels is in an oxidized form, most likely accounting for the good electrochemical response of the hydrogels observed in physiological buffer. In vitro cell studies showed that cardiac cells respond differently when seeded on hydrogel substrates with different compositions. This study presents a facile approach for the fabrication of electroconductive hydrogels with a range of properties, paving the way for scaffolds that can meet the requirements of different electroresponsive tissues.

Despite the latest advances in cardiovascular biology and medicine, myocardial infarction (MI) remains one of the major causes of deaths worldwide. While reperfusion of the myocardium is critical to limit the ischemic damage typical of a MI event, it causes detrimental morphological and functional changes known as “reperfusion injury.” This complex scenario is poorly represented in currently available models of ischemia/reperfusion injury, leading to a poor translation of findings from the bench to the bedside. However, more recent bioengineered in vitro models of the human heart represent more clinically relevant tools to prevent and treat MI in patients. These include 3D cultures of cardiac cells, the use of patient‐derived stem cells, and 3D bioprinting technology. This review aims at highlighting the major features typical of a heart attack while comparing current in vitro, ex vivo, and in vivo models. This information has the potential to further guide in developing novel advanced in vitro cardiac models of ischemia/reperfusion injury. It may pave the way for the generation of advanced pathophysiological cardiac models with the potential to develop personalized therapies.