3-Dimensional Bioprinting of Cardiovascular Tissues: Emerging Technology

Abstract

Three-dimensional (3D) bioprinting may overcome challenges in tissue engineering. Unlike conventional tissue engineering approaches, 3D bioprinting has a proven ability to support vascularization of larger scale constructs and has been used for several cardiovascular applications. An overview of 3D bioprinting techniques, in vivo translation, and challenges are described.

Keywords: 3-dimensional; 3D, 3-dimensional; ECM, extracellular matrix; HUVEC, human umbilical vein endothelial cell(s); MSC, mesenchymal stem cell(s); UV, ultraviolet; bioink; bioprinting; cardiovascular disease; hCPC, human cardiac-derived progenitor cell(s); hiPSC, human induced-pluripotent stem cell(s); regenerative medicine; tissue engineering.

Graphical abstract

Central Illustration

3D Bioprinting Overview (Upper panel) Several key components and considerations are needed when designing a 3-dimensional (3D) bioprinting method. (Lower panel) A sample workflow of incorporating clinical imaging into personalized 3D bioprinting is provided. 3D digital prototype models of organs or tissues are generated from image DICOMs (Digital Imaging and Communications in Medicine) and are used in 3D bioprinting for personalized printed structures. DICOMs are universal file types that encode image data acquired from modalities such as computed tomography, magnetic resonance, and ultrasound.

Figure 1

Publications Search We identified 44 original research papers related to 3-dimensional (3D) bioprinting of cardiovascular constructs. The summary chart was adapted from the PRISMA (Preferred Reporting Systems for Systematic Reviews and Meta-Analyses) (24).

Figure 2

Steps Involved in Extrusion-Based Printing, Scaffold-Free Printing, Non-Extrusion–Based Printing (A) Traditional extrusion-based printing uses a formulated bioink that gets deposited by a cartridge in a layer-by-layer fashion to form a 3-dimensional (3D) structure. (B) Scaffold-free printing is a new generation of 3D bioprinting that requires culturing cells. The cells eventually clump and produce native extracellular matrix, forming spheroids. The spheroids may then be placed one-by-one onto a temporary support beams until the spheroids integrate with each other. The temporary support beams may then be removed forming the final structure. (C) Non-extrusion–based printing such as stereolithography uses light to cure a biomaterial into its desired structure. Because many non-extrusion–based printing techniques induce harsh conditions, cells are often seeded onto a pre-printed scaffold.

Figure 3

Distribution of Cardiovascular 3D Bioprinting Methods Research groups have predominantly opted for extrusion-based methods due to the technique’s favorable conditions such as maintaining cell viability and flexibility in handling different biocompatible materials. 3D = 3-dimensional.