Considerations for the Bioengineering of Advanced Cardiac In Vitro Models of Myocardial Infarction

Abstract

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.

Long non-coding RNA growth arrest specific transcript 5 acting as a sponge of MicroRNA-188-5p to regulate SMAD family member 2 expression promotes myocardial ischemia-reperfusion injury

“…Currently, the most effective way to save AMI is to perform mechanical revascularization [ 3 ]. But amid revascularization, myocardial ischemia reperfusion injury (MIRI) will inevitably appear, leading to increased pro-inflammatory factors and cardiomyocyte apoptosis [ 4 , 5 ]. Therefore, saving pro-inflammatory programmed cardiomyocyte apoptosis has become a research hotspot for improving MIRI.…”

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

“…Three-dimensional cell cultures and technologies are rapidly gaining recognition for their potential to model heart tissue pathophysiology [4,[8][9][10][11]. Cells can be grown in scaffolds, scaffold-free or matrices environment aiming to mimic the ECM features of the heart; for example, biomaterial scaffolds, such as collagen and fibrin, provide a 3D environment for cells to attach, interact with each other and conduct electrical signals [4,6,7,12]. Cardiac myocytes cultured in 3D often employ a biomaterial such as a hydrogel or biocompatible polymer to mimic the ECM, providing a 3D architecture for cells to interact in all spatial dimensions, both with other cells and their environment.…”

“…More physiological constructs require a vascular network that supports flow throughout the entire structure. Bioprinting uniquely offers this feature of manufacturing complex and organized networks to enable nutrient delivery for the efficient cardiac function, waste and oxygen transport, all aimed at promoting cell survival and function [4,7]. This can be accomplished by bioprinting a hydrogel containing a removable internal structure, such as sacrificial polymer or spheroids, yielding hollow networks that can be populated with ECs to mimic in vivo vasculature [31][32][33].…”

“…The application of bioprinted cardiac tissues potentiates the creation of functional cardiac tissue to regenerate or replaced damaged tissue in the myocardium [37,41,42]. In a similar effort to the one used by other approaches aimed at bioengineering the cardiac tissue, these bioprinted tissues better mimic structural, physiological, and functional features of the native myocardium, all features that can be applied for drug testing, toxicity assays and disease modelling (e.g., myocardial infarction and heart failure [7,29,43]). This approach allows the generation of a complex 3D structure permissive for tightly-regulated molecular and cellular interactions, by supporting cells and enhancing their structural reorganisation into functional cardiac tissues [44].…”

“…However, the lack of translation from the bench to the bedside, caused by limitations of currently available in vitro and in vivo models, has prompted a need to engineer novel tools for cardiovascular research. In the past two decades, 3D bioprinting technology has emerged as a potential tool to address limitations of conventional models by generating complex multicellular systems using cells and biomaterials A d v a n c e d o n l i n e a r t i c l e that better recapitulate the human heart microenvironment [4,6,7]. More recently, together with the use of stem cells, advances in the field of biofabrication enabled a move toward advanced in vitro models for drug testing.…”