Bioprinting approaches in cardiac tissue engineering to reproduce blood-pumping heart function

Abstract

The heart, with its complex structural and functional characteristics, plays a critical role in sustaining life by pumping blood throughout the entire body to supply nutrients and oxygen. Engineered heart tissues have been introduced to reproduce heart functions to understand the pathophysiological properties of the heart and to test and develop potential therapeutics. Although numerous studies have been conducted in various fields to increase the functionality of heart tissue to be similar to reality, there are still many difficulties in reproducing the blood-pumping function of the heart. In this review, we discuss advancements in cells, biomaterials, and biofabrication in cardiac tissue engineering to achieve cardiac models that closely mimic the pumping function. Moreover, we provide insight into future directions by proposing future perspectives to overcome remaining challenges, such as scaling up and biomimetic patterning of blood vessels and nerves through bioprinting.

Keywords: Bioengineering; Biomaterials; Cardiovascular medicine; Tissue engineering.

Graphical abstract

Figure 1

Key elements necessary for achieving blood-pumping heart model

Figure 2

Reproduction of cellular heterogeneity by developing engineered heart tissue models consisting of various cardiac cells (A) Schematic illustrating heterogeneous cellular composition of adult human heart. (Reproduced with permission. Copyright 2020, Springer Nature.). (B) Distinct action potential waveform for different cardiomyocytes (Reproduced with permission. Copyright 2020, BioMed Central Ltd.). (C) Bioprinting of pacemaker cells to control the initial point of contraction (Reproduced with permission. Copyright 2019, Elsevier B.V.). (D) EHT developed using iPSC derived endothelial cells and pericytes and the role of pericytes in pathophysiological properties (Reproduced with permission. Copyright 2020, MDPI.). (E) EHT developed using iPSC derived macrophages, which improves cardiac functions (Reproduced with permission. Copyright 2024, Elsevier Inc.).

Figure 3

Functional biomaterials to provide native-like microenvironment and improve cardiac function (A) Decellularized extracellular matrix (dECM)-based hydrogel, faithfully replicating the structures and composition of the natural heart ECM, showing high cell viability and functionality (Reproduced with permission. Copyright 2014, Springer Nature.). (B) Superiority of decellularized extracellular matrix in EHT fabrication compared to other biomaterials (Reproduced with permission. Copyright 2024, Springer Nature.). (C) Visible-light activated photoinitiator enabling the fabrication of dECM-based bioink into large and complex constructs with high shape fidelity (Reproduced with permission. Copyright 2021, John Wiley & Sons.). (D) Incorporation of conductive materials enhancing the electrophysiological functions of the tissue (Reproduced with permission. Copyright 2021, Elsevier B.V.).

Figure 4

Reconstruction of diverse heart chamber structure exhibiting chamber-like functions (A) Chamber-like model created by using molding method, producing volume-pressure dynamics (Reproduced with permission. Copyright 2018, Elsevier B.V.). (B) In-bath printed chamber-like model display thick cardiac tissue with perfusable vasculatures (Reproduced with permission. Copyright 2019, John Wiley & Sons.). (C) Cardiac chamber-like structure formed by rolling cell sheets with diverse orientations, demonstrating volume-pressure dynamics (Reproduced with permission. Copyright 2022, John Wiley & Sons.). (D) Heart chamber tissue mimicking hierarchical myocardial fiber orientation through bioprinting-assisted tissue assembly, resulting in the reproduction of left ventricular twists (Reproduced with permission. Copyright 2024, John Wiley & Son).

Figure 5

Engineered heart component tissues supporting cardiac function (A) Electrospun engineered heart valves, showing native valve-like fluidic flow functions under hemodynamic pressures (Reproduced with permission. Copyright 2023, Elsevier B.V.). (B) Scalable and perfusable vascular tissues generated via coaxial-based bioprinting, allowing for diversity in various structures (Reproduced with permission. Copyright 2018, John Wiley & Sons. Reproduced with permission; Copyright 2020, John Wiley & Sons.). (C) Complex microvasculatures created by bioprinting enabling adequate oxygen supply and exhibiting compartmentalized EC layers (Reproduced with permission. Copyright 2019, John Wiley & Sons.).