Three-dimensional bioprinting and tissue fabrication: prospects for drug discovery and regenerative medicine

Figures & data

Figure 1 Schematics of the major bioprinting mechanisms.

Table 1 Comparison of major bioprinting techniques

Category	Inkjet	Microextrusion	Laser printing
Material viscosity (mPa/s)	Low (3–12)	High (30–6 × 10^7)	1–300
Gelation/cross-linking methods	Chemical or photo–cross–linking, temperature	Chemical or photo–cross–linking, temperature	Chemical or photo–cross–linking
Print speed	1–10,000 droplets/s	10–50 μm/s	200–1600 mm/s
Resolution	50–300 μm wide droplets	100 μm to 1 mm wide	50
Accuracy	Medium	Medium–low	High
Cell viability	>85%	40%–80%	>85%
Cell density	10^6–10^7 cells/mL	High: cell spheroids	10^6–10^7 cells/mL
Biomaterials used	Hydrogels, fibrin, agar, collagen, alginate	Hyaluronic acid, gelatin, alginate, collagen, fibrin	Hydrogels, nano–hydroxyapatite
Mechanical/structural integrity	Low	High	Low
Fabrication time	Medium	Short	Long
Scalability	Yes	Yes	Limited
Cost	Low	Medium	High
Example applications	Skin,^Citation22,Citation53 vascular,^Citation65,Citation66,Citation69 cartilage^Citation46,Citation78,Citation79	Trachea,^Citation38,Citation71 cardiac valve^Citation75^–^Citation77	Skin^Citation54,Citation55

Table 2 List of commonly used biomaterials for bioprinting

Materials	Synthetic or natural	Gelation mechanisms	Gelation speed	Advantages	Disadvantages
Acrylated PEG or multi-arm PEG	Synthetic	Photopolymerization	Seconds-minutes	Easy to control mechanical properties	No biological activities, needs modification
Collagen	Natural	pH and temperature	Hours	Natural bioactivity, major component of native ECM	Slow gelation, lacks mechanical properties
Thiolated hyaluronic acid	Natural	pH-mediated Michael addition	Minutes-hours	Commercially available in kit with gelation for cell adherence	Weak mechanical properties
Thiolated hyaluronic acid	Natural	Photopolymerization thiol-ene	Seconds	Easily controllable, fast gelation	Weak mechanical properties
Methacrylated hyaluronic acid	Natural	Photopolymerization	Minutes	Gelation speed modulated by UV intensity	Weak mechanical properties
Tyramine hyaluronic acid	Natural	Chemical cross-linking (oxidative coupling, tyramine–H2O2)	Seconds	Fast gelling	Difficult to control geometry due to fast gelation
Gelatin	Natural	Temperature	Minutes-hours	Natural cell adherent	Unstable
Methacrylated gelatin	Natural	Photopolymerization	Minutes	Natural cell adherent	Weak mechanical properties
Alginate	Natural	Chemical cross-linking (Ca^2+)	Seconds	Easy to create gel microspheres	Difficult to control geometry, no cell adherent without modification
Fibrin	Natural	Enzymatic reaction (thrombinfibrinogen)	Seconds	Cell adherent	Difficult to control geometry
PCL	Synthetic	Melt by high temperature	Seconds	Robust mechanical properties	High temperature, incompatible with cells

Abbreviations: ECM, extracellular matrix; PCL, polycaprolactone; PEG, polyethylene glycol; UV, ultraviolet.

Figure 2 Examples of the bioprinted tissues.

Notes: (A) 3D-printed, porous PCL scaffolds of maxilla at 40% infill density. Copyright © 2014. John Wiley and Sons. Reproduced from Temple JP, Hutton DL, Hung BP, et al. Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds. J Biomed Mater Res A. 2014;102(12):4317–4325.⁴³ (B) Schematic of bioprinting cell-laden constructs for cartilage tissue engineering with simultaneous photopolymerization process. Copyright © 2012. John Wiley and Sons. Reproduced from Cui X, Breitenkamp K, Lotz M, D’Lima D. Synergistic action of fibroblast growth factor-2 and transforming growth factor-beta1 enhances bioprinted human neocartilage formation. Biotechnol Bioeng. 2012; 109(9):2357–2368.⁴⁷ (C) 3D-printed skin tissue with keratinocyte-populated epidermal layer and fibroblast-populated dermal layer. Scale bar, 500 μm. Copyright © 2014, Mary Ann Liebert, Inc. Reproduced from Lee V, Singh G, Trasatti JP, et al. Design and fabrication of human skin by three-dimensional bioprinting. Tissue Eng Part C Methods. 2014;20(6):473–484.⁵³ (D) 3D vascular network (red) with 10T1/2 cells (green) in the interstitial space. Scale bar, 1 mm. Reprinted by permission from Macmillan Publishers Ltd: Nature Materials. Miller JS, Stevens KR, Yang MT, et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater. 2012;11(9):768–774, copyright © 2012.⁶¹ (E) Bioprinting of aortic valve conduit with dual cell types for valve root (green, smooth muscle cells) and valve leaflets (red, valve leaflet interstitial cells). Copyright © 2013. John Wiley and Sons. Reproduced from Duan B, Hockaday LA, Kang KH, Butcher JT. 3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. J Biomed Mater Res A. 2013;101(5):1255–1264.⁷⁵
Abbreviations: HUVEC, human umbilical vein endothelial cell; PCL, polycaprolactone; PEGDMA, polyethylene glycol dimethacrylate; 3D, three-dimensional; EGFP, enhanced green fluorescent protein.

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 Web of Science ®Google Scholar

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