Current methods for fabricating 3D cardiac engineered constructs

Abstract

3D cardiac engineered constructs have yielded not only the next generation of cardiac regenerative medicine but also have allowed for more accurate modeling of both healthy and diseased cardiac tissues. This is critical as current cardiac treatments are rudimentary and often default to eventual heart transplants. This review serves to highlight the various cell types found in cardiac tissues and how they correspond with current advanced fabrication methods for creating cardiac engineered constructs capable of shedding light on various pathologies and providing the therapeutic potential for damaged myocardium. In addition, insight is given toward the future direction of the field with an emphasis on the creation of specialized and personalized constructs that model the region-specific microtopography and function of native cardiac tissues.

Keywords: 3d reconstruction of protein; Biomaterials; Materials science.

Graphical abstract

Figure 1

The general concept of hPSCs-derived cardiac engineered constructs for medical applications hiPSCs sourced from patients are applied for differentiating into various cardiovascular cell lineages, which are further incorporated with specific engineering techniques to fabricate the heart tissue construct that emulates the structure and function of cardiac tissue in vivo. These constructs are then specified to the targeted biomedical applications of modeling and treating cardiac diseases. Created with BioRender.com.

Figure 2

Engineering methods for fabricating 3D cardiac engineered constructs Micropatterning: cells are aligned on a substrate by the guidance of grooves or other pattern techniques. Hydrogel: a polymer is chosen as base material and mixed with cells to form a gel, which is then hardened to desired stiffness through crosslinking. Electrospinning: a polymer solution is ejected onto a platform to form a fibrous scaffold. Cells are seeded on the scaffold. Decellularization: cells are stripped from natural tissues by surfactants and replaced with cells from the patient. Engineered heart tissue: CMs are suspended and attached in an aligned fashion. 3D bioprinting: layered printing of cells in hydrogels (“bio-ink”) to produce a detailed scaffold with mechanical assistance. Scaffold-free: the depicted patterning is organized using acoustic waves to move cells. Organoid: aggregates of pluripotent stem cells in ultralow attachment well plates are differentiated into cardiac tissues. Created with BioRender.com.

Figure 3

Overview of fabrication methods and applications for cardiac engineered constructs First, human pluripotent stem cells are sourced from donors through reprogramming or from direct extraction as embryonic stem cells. The pluripotent stem cells are then differentiated into various cardiac-specific cell types, such as the myocardium (fibroblasts, cardiomyocytes), vasculature (endothelial, smooth muscle), and immune cells. The derived cells are then combined with various fabrication methods, ranging from the use of additive biopolymers to utilizing natural components to generate ECM-like scaffolds using biocompatible materials. The use of these engineering methods enables growth and maturation of the cell culture to generate a cardiac engineered construct, some of which are capable of replicating chamber-specific conditions. The cardiac engineered constructs maintain important properties of in vivo tissues, allowing for various applications. These include (but are not limited to): the creation of in vitro disease models, evaluation of drug efficacy through screening, and regenerative therapies such as through cardiac patches. Created with BioRender.com.