Towards engineering heart tissues from bioprinted cardiac spheroids

Abstract

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.

A New Versatile Platform for Assessment of Improved Cardiac Performance in Human-Engineered Heart Tissues

“…Since EHTs in MM+HS performed best, future improvements of culture medium could be made by evaluating which factors in horse serum contribute to a better performance. The design of the EHT platform enabled us to rapidly screen multiple culture medium conditions, a trait that makes it well-suited to systematically study other maturation factors, such as the effect of multicellularity in various ratios and both combinations and adaptations in energy sources as already described [13,[42][43][44], with contractile force as a major functional readout. Improvements in developing robust and mature hiPSC-EHTs will not only lead to a better understanding of the underlying mechanisms of cardiac maturation but will also serve as a platform for studying contractile function in patient-specific diseases, which, in addition to the cardiovascular field, can also be extended to the skeletal muscle field.…”

A World-First Surgical Instrument for Minimally Invasive Robotically-Enabled Transplantation of Heart Patches for Myocardial Regeneration: A Brief Research Report

“…Then trials will be needed for a functional demonstration of a clinically and statistically significant improvement in cardiac function (including non-inferiority against the alternative approach of traditional open surgery). Whilst this brief report article has focused on a surgical instrument design, significant work will also be needed to show that the patch matrix we proposealginate 4%/gelatin 8% patches ± cells based on our previous optimisation for cardiac applications (9,16,18)-is superior to reference patch materials. Translating these technologies is a lengthy process, which is part of the point: it should happen in parallel to the advancements currently underway in the field of myocardial regeneration, or the field risks unveiling a successful new treatment to a world that might have moved away from traditional open surgery (2,19), limiting how to actually deliver it.…”

Current state and future of 3D bioprinted models for cardio-vascular research and drug development

“…However, in addition to biological factors, a major challenge of in vitro cardiac tissues is their ability to respond to mechanical and electrical simulations in 3D [28]. In our latest study, we developed a novel approach for the biofabrication of 3D bioprinted heart tissues using bioinks containing alginate/gelatin (Al/Ge) hydrogels and 3D cardiac spheroids (CSs) [50].…”

“…However, in addition to biological factors, a major challenge of in vitro cardiac tissues is their ability to respond to mechanical and electrical simulations in 3D [ 28 ]. In our latest study, we developed a novel approach for the biofabrication of 3D bioprinted heart tissues using bioinks containing alginate/gelatin (Al/Ge) hydrogels and 3D cardiac spheroids (CSs) [ 50 ]. Cardiac spheroids were first created from human cardiac myocytes, fibroblasts and endothelial cells and then mixed within optimal Al/Ge hydrogels before being tested for viability and contractile function in vitro .…”