3D printing approaches for cardiac tissue engineering and role of immune modulation in tissue regeneration

Figures & data

Figure 1 Cell therapy to treat MI, isolation, injection, repair, and apoptosis.

Abbreviations: HGF, human growth factor; MI, myocardial infarction; MSC, mesenchymal stem cell; VEGF, vascular endothelial growth factor.

Figure 2 Graphical representation of challenges in cardiac tissue engineering.

Table 1 Scaffolds/materials used in 3D printing of cardiac and microvascular structures

Materials	Scaffold types/approach	Properties	3D printing method	References
PCL	Hydrogel/nanofibers	Moderate mechanical strength. Biocompatible and degraded easily	Inkjet/extrusion	^Citation28, ^Citation31, ^Citation78
PCL-CNT	Nanofibers	High mechanical strength and electrical conductance	Extrusion/laser	^Citation78
PLGA	Hydrogel/nanofibers	Brittle and relatively hard. Not good for tissue remodeling. Biocompatible and biodegradable, immunogenic	Droplet	^Citation82, ^Citation207
Gelatin	Hydrogel/cell layers	Biocompatible, biodegradable, low cell adhesion and viability. Good printability, high cell viability and cross-linking agents. Low mechanical strength. Immunogenic	Extrusion/droplet	^Citation81, ^Citation102, ^Citation130, ^Citation131, ^Citation148
Chitosan	Spheroids/hydrogel/nanofibers	Biocompatible, biodegradable, immunogenic, high cell proliferation and cell remodeling, low mechanical strength, and antibacterial	Extrusion/laser	^Citation32, ^Citation50, ^Citation55, ^Citation86
Fibrin	Hydrogel/nanofibers/cell sheets	High cell adhesion and viability, quick gelation and low printability, biocompatibility, low mechanical strength, good cell migration, and vascularization	Extrusion	^Citation131, ^Citation134, ^Citation135, ^Citation144, ^Citation147, ^Citation208
Alginate	Hydrogel/microdroplet	Biocompatible, biodegradable, sustained release, adoptable mechanical strength with cell growth, rapid gelation, low cell adhesion, can be increased by surface modification with collagen type I	Extrusion/droplet	^Citation83, ^Citation127, ^Citation148
Hyaluronic acid Hyaluronic acid/gelatin	Hydrogel	Biocompatible, biodegradable, low mechanical strength, high cell proliferation and viability, high printability	Extrusion/inkjet	^Citation102
Decellularized extracellular matrix reinforced with PCL framework	Hydrogel	High cell viability, high cell adhesion, and maturation. Easily synchronized with grafted tissues, good printability, and mechanical strength. No immune reaction. Biocompatible	Extrusion/droplet	^Citation56, ^Citation57, ^Citation149, ^Citation150
Collagen	Hydrogel	High biocompatibility, biodegradable, high cell adhesion, and cell remodeling. Has high printability and acts as signal transducer and good in electromechanical coupling with host tissues	Extrusion/droplet	^Citation29, ^Citation76, ^Citation134
NIPAM	Hydrogel/nanofibers/cell sheets	Thermosensitive, sustained release, biocompatible, can be made biodegradable, low mechanical strength, can be modified easily with various functional groups	Laser	^Citation29, ^Citation35
Poly(ethylene glycol)	Hydrogel	Biocompatible, biodegradable, poor cell adhesion and proliferation, moderate mechanical strength, low printability, can be modified with various functional groups	Extrusion	^Citation83

Abbreviations: CNT, carbon nanotube; PCL, polycaprolactone; PLGA, poly(lactic-co-glycolic acid); NIPAM, N-isopropylacrylamide.

Figure 3 Comparison of conventional and modern 3D printed scaffold-based tissue engineering techniques: (A) decellularization, (B) hydrogels, (C) nanofibers, (D) spheroids and hydrogel hybrid bioprinting, (E) 3D scaffold printing, and (F) 3D printed microfluidics chip.

Abbreviation: 3D, three-dimensional.

Figure 4 Process of 3D bioprinting, (A) steps of 3D bioprinting, (B) pre-scaffold fabrication bioprinting, (C) simultaneous hybrid 3D bioprinting.

Abbreviations: 3D, three-dimensional; CAD, computer-aided design; PCL, polycaprolactone; hdECM, heart decellularized-extracellular matrix; cdECM, cartilage decellularized-extracellular matrix; adECM, adipose decellularized-extracellular matrix.

Figure 5 3D bioprinting technology and its types.

Abbreviations: 3D, three-dimensional; UV, ultraviolet.

Figure 6 Conventional vs 3D microfluidics-based drug screening model for cardiotoxicity testing.

Abbreviation: 3D, three-dimensional.

Figure 7 Multiple immunologic reactions during tissue repair and regeneration process.

Notes: Biomaterials-based tissue-engineered scaffolds are developed to deliver molecules, which promote regenerative pathways rather than proinflammatory pathways. Reprinted from Acta Biomater, 53, Julier Z, Park AJ, Briquez PS, Martino MM, Promoting tissue regeneration by modulating the immune system, 13–28, Copyright (2017), with permission from Elsevier.¹⁹⁷

Abbreviations: ECM, extracellular matrix; IFN, interferon; IGF, insulin-like growth factor; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor.

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