Advances in three-dimensional bioprinted stem cell-based tissue engineering for cardiovascular regeneration

Abstract

Three-dimensional (3D) bioprinting of cellular or biological components are an emerging field to develop tissue structures that mimic the spatial, mechanochemical and temporal characteristics of cardiovascular tissues. 3D multi-cellular and multi-domain organotypic biological constructs can better recapitulate in vivo physiology and can be utilized in a variety of applications. Such applications include in vitro cellular studies, high-throughput drug screening, disease modeling, biocompatibility analysis, drug testing and regenerative medicine. A major challenge of 3D bioprinting strategies is the inability of matrix molecules to reconstitute the complexity of the extracellular matrix and the intrinsic cellular morphologies and functions. An important factor is the inclusion of a vascular network to facilitate oxygen and nutrient perfusion in scalable and patterned 3D bioprinted tissues to promote cell viability and functionality. In this review, we summarize the new generation of 3D bioprinting techniques, the kinds of bioinks and printing materials employed for 3D bioprinting, along with the current state-of-the-art in engineered cardiovascular tissue models. We also highlight the translational applications of 3D bioprinting in engineering the myocardium cardiac valves, and vascular grafts. Finally, we discuss current challenges and perspectives of designing effective 3D bioprinted constructs with native vasculature, architecture and functionality for clinical translation and cardiovascular regeneration.

Keywords: 3D bioprinting; Cardiovascular; Extrusion; Inkjet; Preclinical models; Stem cells; Tissue engineering.

Figure 1.. 3D bioprinting techniques and the resulting bioprinted tissues.

(A) Inkjet-based bioprinting, where loaded bioink is dispensed and the bioink jet breaks into small inkjets (adapted with permission from [90]), (B) Extrusion-based bioprinting, where bioink is deposited as cylindrical filaments (adapted with permission from [90], (C) Laser-based bioprinting where the bioink is transferred as jet inkjets using laser energy (adapted with permission from [90]. (D) Aspiration-based bioprinting (adapted with permission from [91]). (E) Optical images showing bioprinted cardiac patches using Kenzan technique (adapted with permission from [77]). (F) Optical and dark-field images of the 3D printed heart using FRESH method with internal structures (adapted with permission from [86]). (G) Confocal images of bioprinted dECM tissues constructs after 7 days (adapted with permission from [92]). (H) In vitro characterization of the 4D hydrogel-based cardiac patches using laser-based bioprinting (adapted with permission from [93]). (I) In vitro characterization of perfusable cardiac tissues using SWIFT (adapted with permission from [87]).