Bioprinting of Multimaterials with Computer-aided Design/Computer -aided Manufacturing

J. M. Lee, S. L. Sing, W. Y. Yeong

Article ID: 245
Vol 6, Issue 1, 2020, Article identifier:245

VIEWS - 1576 (Abstract) 226 (PDF)


Multimaterials deposition, a distinct advantage in bioprinting, overcomes material’s limitation in hydrogel-based bioprinting. Multimaterials are deposited in a build/support configuration to improve the structural integrity of three-dimensional bioprinted construct. A combination of rapid cross-linking hydrogel has been chosen for the build/support setup. The bioprinted construct was further chemically cross-linked to ensure a stable construct after print. This paper also proposes a file segmentation and preparation technique to be used in bioprinting for printing freeform structures.


3D bioprintin; Bioprinting; Hydrogel; 3D printing; Rapid prototyping; Additive manufacturing; Computer aided design; Support structures

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Zhuang P, Sun AX, An J, et al., 2018, 3D Neural Tissue Models: From Spheroids to Bioprinting. Biomaterials, 154:113–133. DOI: 10.1016/j.biomaterials.2017.10.002.

Ng WL, Chua CK, Shen YF, 2019, Print Me An Organ! Why We Are Not There Yet. Prog Polym Sci, 97:101145. DOI: 10.1016/j.progpolymsci.2019.101145.

Kolan KCR, Semon JA, Bromet B, et al., 2019, Bioprinting with Human Stem Cells-Laden Alginate-gelatin Bioink and Bioactive Glass for Tissue Engineering. Int J Bioprint, 5:13. DOI: 10.18063/ijb.v5i2.2.204.

Xu T, Zhao W, Zhu JM, et al., 2013, Complex Heterogeneous Tissue Constructs Containing Multiple Cell Types Prepared by Inkjet Printing Technology. Biomaterials, 34:130–139. DOI: 10.1016/j.biomaterials.2012.09.035.

Guillemot F, Guillotin B, Fontaine A, et al., 2011, Laser assisted Bioprinting to Deal with Tissue Complexity in Regenerative Medicine. MRS Bull, 36:1015–1019. DOI: 10.1557/mrs.2011.272.

Lee YB, Polio S, Lee W, et al., Bio-printing of Collagen and VEGF-Releasing Fibrin Gel Scaffolds for Neural Stem Cell Culture. Exp Neurol, 223:645–652. DOI: 10.1016/j.expneurol.2010.02.014.

Skardal A, Mack D, Kapetanovic E, et al., 2012, Bioprinted Amniotic Fluid-derived Stem Cells Accelerate Healing of Large Skin Wounds. Stem Cells Transl Med, 1:792–802. DOI: 10.5966/sctm.2012-0088.

Ozbolat IT, Hospodiuk M, 2016, Current Advances and Future Perspectives in Extrusion-based Bioprinting. Biomaterials, 76:321–343. DOI: 10.1016/j.biomaterials.2015.10.076.

Lee H, Ahn S, Bonassar LJ, et al., 2013, Cell-laden Poly(varepsilon-Caprolactone)/Alginate Hybrid Scaffolds Fabricated by an Aerosol Cross-Linking Process for Obtaining Homogeneous Cell Distribution: Fabrication, Seeding Efficiency, and Cell Proliferation and Distribution. Tissue Eng Part C Methods, 19:784–793. DOI: 10.1089/ten.tec.2012.0651.

Billiet T, Gevaert E, De Schryver T, et al., 2014, The 3D Printing of Gelatin Methacrylamide Cell-laden Tissue engineered Constructs with High Cell Viability. Biomaterials, 35:49–62. DOI: 10.1016/j.biomaterials.2013.09.078.

Duan B, Hockaday LA, Kang KH, et al., 2013, 3D Bioprinting of Heterogeneous Aortic Valve Conduits with Alginate/Gelatin Hydrogels. J Biomed Mater Res A, 101:1255–1264. DOI: 10.1002/jbm.a.34420.

Fedorovich NE, Wijnberg HM, Dhert WJ, et al., 2011, Distinct Tissue Formation by Heterogeneous Printing of Osteo and Endothelial Progenitor Cells. Tissue Eng Part A, 17:2113–2121. DOI: 10.1089/ten.tea.2011.0019.

Huang Y, He K, Wang X, 2013, Rapid Prototyping of a Hybrid Hierarchical Polyurethane-Cell/Hydrogel Construct for Regenerative Medicine. Mater Sci Eng C Mater Biol Appl, 33:3220–3229. DOI: 10.1016/j.msec.2013.03.048.

Ozbolat IT, Chen H, Yu Y, 2014, Development of “Multi-Arm Bioprinter” for Hybrid Biofabrication of Tissue Engineering Constructs. Robot. Comput. Integr. Manuf, 30:295–304. DOI:10.1016/j.rcim.2013.10.005.

Shim JH, Lee JS, Kim JY, et al., 2012, Bioprinting of a Mechanically Enhanced Three-dimensional Dual Cell-Laden Construct for Osteochondral Tissue Engineering Using a Multi-Head Tissue/Organ Building System. J Micromech Microeng, 22:085014. DOI: 10.1088/0960-1317/22/8/085014.

Snyder JE, Hamid Q, Wang C, et al., 2011, Bioprinting Cellladen Matrigel for Radioprotection Study of Liver by Pro-drug Conversion in a Dual-tissue Microfluidic Chip. Biofabrication, 3:034112. DOI: 10.1088/1758-5082/3/3/034112.

Visser J, Peters B, Burger TJ, et al., 2013, Biofabrication of Multimaterial Anatomically Shaped Tissue Constructs. Biofabrication, 5:035007. DOI: 10.1088/1758-5082/5/3/035007.

Lee W, Lee V, Polio S, et al., 2009, Three-dimensional Cell hydrogel Printer Using Electromechanical Microvalve for Tissue Engineering. In: Solid-State Sensors, Actuators and Microsystems Conference, 2009. TRANSDUCERS 2009, pp. 2230-2233. DOI: 10.1109/sensor.2009.5285591.

Zhuang P, Ng WL, An J, et al., Layer-by-layer Ultraviolet Assisted Extrusion-based (UAE) Bioprinting of Hydrogel Constructs with High Aspect Ratio for Soft Tissue Engineering Applications. PLoS One, 14:e0216776. DOI: 10.1371/journal.pone.0216776.

Peppas NA, Hilt JZ, Khademhosseini A, et al., 2006, Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology. Adv Mater, 18:1345-1360.DOI: 10.1002/adma.200501612.

O’Brien FJ, 2011, Biomaterials and Scaffolds for Tissue Engineering. Mater Today, 14:88–95.

Place ES, Evans ND, Stevens MM, 2009, Complexity in Biomaterials for Tissue Engineering. Nat Mater, 8:457–470.

Hubbell JA, 1995, Biomaterials in Tissue Engineering. Nat Biotech, 13:565–576.

Malda J, Visser J, Melchels FP, et al., 2013, 25th Anniversary Article: Engineering Hydrogels for Biofabrication. Adv. Mater, 25:5011–5028. DOI: 10.1002/adma.201302042.

Lee JM, Yeong WY, 2016, Design and Printing Strategies in 3D Bioprinting of Cell-Hydrogels: A Review. Adv Healthc Mater, 5:2856–2865. DOI: 10.1002/adhm.201600435.

Takagi D, Lin W, Matsumoto T, et al., 2019, High-precision 3D Inkjet Technology for Live Cell Bioprinting. Int J Bioprint, 5:208. DOI: 10.18063/ijb.v5i2.208.

Tan HW, Tran T, Chua CK, 2016, A Review of Printed Passive Electronic Components Through Fully Additive Manufacturing Methods. Virtual Phys Prototyp, 11:271–288. DOI: 10.1080/17452759.2016.1217586.

Saengchairat N, Tran T, Chua CK, 2017, A Review: Additive Manufacturing for Active Electronic Components. Virtual Phys Prototyp, 12:31–46. DOI: 10.1080/17452759.2016.1253181.

Yap YL, Yeong WY, 2015, Shape Recovery Effect of 3D Printed Polymeric Honeycomb. Virtual Phys Prototyp, 10:91–99.

Francis V, Jain PK, 2016, Experimental Investigations on Fused Deposition Modelling of Polymer-layered Silicate Nanocomposite. Virtual Phys Prototyp, 11:109–121. DOI: 10.1080/17452759.2016.1172431.

Meisel N, Williams C, 2015, An Investigation of Key Design for Additive Manufacturing Constraints in Multimaterial Three-Dimensional Printing. J Mech Des, 137:111406. DOI: 10.1115/1.4030991.

Gan MX, Wong CH, 2016, Practical Support Structures for Selective Laser Melting. J Mater Processing Technol, 238:474–484. DOI: 10.1016/j.jmatprotec.2016.08.006.

Rodgers LM, 2012, Extrusion-based Additive Manufacturing Process with Part Annealing. Google Patents.

Barnett E, Gosselin C, 2015, Weak Support Material Techniques for Alternative Additive Manufacturing Materials. Addit Manufac, 8:95–104. DOI: 10.1016/j.addma.2015.06.002.

Yap CY, Chua CK, Dong ZL, et al., 2015, Review of Selective Laser Melting: Materials and Applications. Appl Phys Rev, 2:041101.

Loh LE, Chua CK, Yeong WY, et al., 2015, Numerical Investigation and an Effective Modelling on the Selective Laser Melting (SLM) Process with Aluminium Alloy 6061. Int J Heart Mass Transfer, 80:288–300. DOI: 10.1016/j.ijheatmasstransfer.2014.09.014.

Sun Z, Tan X, Tor SB, et al., 2018, Simultaneously Enhanced Strength and Ductility for 3D-printed Stainless steel 316L by Selective Laser Melting. NPG Asia Mater, 10:127–136. DOI: 10.1038/s41427-018-0018-5.

Li Y, Zhou K, Tan P, et al., 2018, Modeling Temperature and Residual Stress Fields in Selective Laser Melting. Int J Mech Sci, 136:24–35.

Tan X, Kok Y, Tan YJ, et al., 2015, Graded Microstructure and Mechanical Properties of Additive Manufactured Ti–6Al–4V Via Electron Beam Melting. Acta Mater, 97:1–16. DOI: 10.1016/j.actamat.2015.06.036.

Yu WH, Sing SL, Chua CK, et al., 2019, Influence of Remelting on Surface Roughness and Porosity of AlSi10Mg Parts Fabricated by Selective Laser Melting. J Alloys Compd, 792:574–581. DOI: 10.1016/j.jallcom.2019.04.017.

Yu WH, Sing SL, Chua CK, et al., 2019, Particle-Reinforced Metal Matrix Nanocomposites Fabricated by Selective Laser Melting: A State of the Art Review. Prog Mater Sci, 104:330– 379. DOI: 10.1016/j.pmatsci.2019.04.006.

Kuo CN, Chua CK, Peng PC, et al., 2020, Microstructure Evolution and Mechanical Property Response via 3D Printing Parameter Development of Al–Sc Alloy. Virtual Phys Prototyp, 15:120–129. DOI: 10.1080/17452759.2019.1698967.

Tey CF, Tan X, Sing SL, et al., Additive Manufacturing of Multiple Materials by Selective Laser Melting: Ti-alloy to Stainless Steel via a Cu-alloy Interlayer. Addit. Manufact, 31:100970. DOI: 10.1016/j.addma.2019.100970.

Tan JHK, Sing SL, Yeong WY, 2020, Microstructure Modelling for Metallic Additive Manufacturing: A Review. Virtual Phys Prototyp, 15:87–105. DOI: 10.1080/17452759.2019.1677345.

Lee JY, Tan WS, An J, et al., 2016, The Potential to Enhance Membrane Module Design with 3D Printing Technology. J Membr Sci, 499:480–490.

Yuan S, Shen F, Chua CK, et al., 2019, Polymeric Composites for Powder-based Additive Manufacturing: Materials and Applications. Prog Polym Sci, 91:141–168. DOI: 10.1016/j.progpolymsci.2018.11.001

Lee JY, An J, Chua CK, 2017, Fundamentals and Applications of 3D Printing for Novel Materials. Appl Mater Today, 7:120–133.

Horváth L, Umehara Y, Jud C, et al., Engineering an in vitro air-blood barrier by 3D bioprinting. Sci Rep, 5:7974.

Merceron TK, Burt M, Seol YJ, et al., 2015, A 3D Bioprinted Complex Structure for Engineering the Muscle-tendon Unit. Biofabrication, 7:035003. DOI: 10.1088/1758-5090/7/3/035003.

Miller JS, Stevens KR, Yang MT, et al., 2012, Rapid Casting of Patterned Vascular Networks for Perfusable Engineered Three-dimensional Tissues. Nat. Mater, 11:768–774. DOI: 10.1038/nmat3357.

Wüst S, Godla ME, Müller R, et al., 2014, Tunable Hydrogel Composite with Two-step Processing in Combination with Innovative Hardware Upgrade for Cell-based Three dimensional Bioprinting. Acta Biomater, 10:630–640. DOI: 10.1016/j.actbio.2013.10.016.

Skardal A, Zhang J, McCoard L, et al., 2010, Photocrosslinkable Hyaluronan-Gelatin Hydrogels for Two-Step Bioprinting. Tissue Eng Part A, 16:2675–2685. DOI:10.1089/ten.tea.2009.0798.

Blaeser A, Campos DF, Puster U, et al., 2016, Controlling Shear Stress in 3D Bioprinting is a Key Factor to Balance Printing Resolution and Stem Cell Integrity. Adv Healthc Mater, 5:326–333. DOI: 10.1002/adhm.201500677.

Kolesky DB, Truby RL, Gladman AS, et al., 3D Bioprinting of Vascularized, Heterogeneous Cell-laden Tissue Constructs. Adv Mater., 26:3124–3130. DOI: 10.1002/adma.201305506.

Hinton TJ, Jallerat Q, Palchesko RN, et al., 2015, Three dimensional Printing of Complex Biological Structures by Freeform Reversible Embedding of Suspended Hydrogels. Sci Adv, 1:e1500758. DOI: 10.1126/sciadv.1500758.

Wu W, DeConinck A, Lewis JA, 2011, Omnidirectional Printing of 3D Microvascular Networks. Adv Mater, 23:H178.

An J, Teoh JE, Suntornnond R, et al., 2015, Design and 3D Printing of Scaffolds and Tissues. Engineering, 1:261–268.

Liu F, Mishbak H, Bartolo PJ, 2019, Hybrid Polycaprolactone/Hydrogel Scaffold Fabrication and in-process Plasma Treatment Using PABS. 5:1–9.

Schuurman W, Khristov V, Pot MW, et al., 2011, Bioprinting of Hybrid Tissue Constructs with Tailorable Mechanical Properties. Biofabrication, 3:021001. DOI: 10.1088/1758-5082/3/2/021001.

Shim JH, Kim JY, Park M, et al., 2011, Development of a Hybrid Scaffold with Synthetic Biomaterials and Hydrogel Using Solid Freeform Fabrication Technology. Biofabrication, 3:034102. DOI: 10.1088/1758-5082/3/3/034102.

Pati F, Jang J, Ha DH, et al., 2014, Printing Three-dimensional Tissue Analogues with Decellularized Extracellular Matrix Bioink. Nat Commun, 5:3935. DOI: 10.1038/ncomms4935.

Kang HW, Lee SJ, Ko IK, et al., 2016, A 3D Bioprinting System to Produce Human-scale Tissue Constructs with Structural Integrity. Nat. Biotechnol, 34:312–319. DOI: 10.1038/nbt.3413.

Skylar-Scott MA, Uzel SG, Nam LL, et al., 2019, Biomanufacturing of Organ-specific Tissues with High Cellular Density and Embedded Vascular Channels. Sci Adv,5:eaaw2459. DOI: 10.1126/sciadv.aaw2459.

Lee A, Hudson AR, Shiwarski DJ, et al., 2019, 3D Bioprinting of Collagen to Rebuild Components of the Human Heart. Science, 365:482–487. DOI: 10.1126/science.aav9051.

Luo G, Yu Y, Yuan Y, et al., 2019, Freeform, Reconfigurable Embedded Printing of All-aqueous 3D Architectures. Adv Mater, 31:1904631. DOI: 10.1002/adma.201904631.

Mirzendehdel AM, Suresh K, 2016, Support Structure Constrained Topology Optimization for Additive Manufacturing. Comput. Aided Des, 81:1–13. DOI: 10.1016/j.cad.2016.08.006.

Nichol JW, Koshy ST, Bae H, et al., 2010, Cell-laden Microengineered Gelatin Methacrylate Hydrogels. Biomaterials, 31:5536–5544. DOI: 10.1016/j.biomaterials.2010.03.064.

Akash MS, Rehman K, 2015, Recent Progress in Biomedical Applications of Pluronic (PF127): Pharmaceutical Perspectives. J Control Release, 209:120–138. DOI:10.1016/j.jconrel.2015.04.032.



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