Journal Home Online First Current Issue Archive For Authors Journal Information 中文版

Engineering >> 2015, Volume 1, Issue 2 doi: 10.15302/J-ENG-2015061

Design and 3D Printing of Scaffolds and Tissues

Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore

Received: 2015-01-30 Revised: 2015-03-23 Accepted: 2015-06-30 Available online: 2015-06-30

Next Previous

Abstract

A growing number of three-dimensional (3D)-printing processes have been applied to tissue engineering. This paper presents a state-of-the-art study of 3D-printing technologies for tissue-engineering applications, with particular focus on the development of a computer-aided scaffold design system; the direct 3D printing of functionally graded scaffolds; the modeling of selective laser sintering (SLS) and fused deposition modeling (FDM) processes; the indirect additive manufacturing of scaffolds, with both micro and macro features; the development of a bioreactor; and 3D/4D bioprinting. Technological limitations will be discussed so as to highlight the possibility of future improvements for new 3D-printing methodologies for tissue engineering.

Figures

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig. 6

References

[ 1 ] R. Langer, J. P. Vacanti. Tissue engineering. Science, 1993, 260(5110): 920−926 link1

[ 2 ] Q. L. Loh, C. Choong. Three-dimensional scaffolds for tissue engineering applications: Role of porosity and pore size. Tissue Eng. Part B Rev., 2013, 19(6): 485−502 link1

[ 3 ] S. Yang, K. F. Leong, Z. Du, C. K. Chua. The design of scaffolds for use in tissue engineering. Part I. Traditional factors. Tissue Eng., 2001, 7(6): 679−689 link1

[ 4 ] S. Yang, K. F. Leong, Z. Du, C. K. Chua. The design of scaffolds for use in tissue engineering. Part II. Rapid prototyping techniques. Tissue Eng., 2002, 8(1): 1−11 link1

[ 5 ] K. F. Leong, C. M. Cheah, C. K. Chua. Solid freeform fabrication of three-dimensional scaffolds for engineering replacement tissues and organs. Biomaterials, 2003, 24(13): 2363−2378 link1

[ 6 ] W. Y. Yeong, C. K. Chua, K. F. Leong, M. Chandrasekaran. Rapid prototyping in tissue engineering: Challenges and potential. Trends Biotechnol., 2004, 22(12): 643−652 link1

[ 7 ] T. Boland, Rapid, prototyping of artificial tissues and medical devices. Adv. Mater. Process., 2007, 165(4): 51−53

[ 8 ] P. J. Bártolo, C. K. Chua, H. A. Almeida, S. M. Chou, A. S. C. Lim. Biomanufacturing for tissue engineering: Present and future trends. Virtual and Physical Prototyping, 2009, 4(4): 203−216 link1

[ 9 ] S. J. Hollister. Porous scaffold design for tissue engineering. Nat. Mater., 2005, 4(7): 518−524 link1

[10] C. M. Cheah, C. K. Chua, K. F. Leong, S. W. Chua. Development of a tissue engineering scaffold structure library for rapid prototyping. Part 1: Investigation and classification. Int. J. Adv. Manuf. Technol., 2003, 21(4): 291−301 link1

[11] C. M. Cheah, C. K. Chua, K. F. Leong, S. W. Chua. Development of a tissue engineering scaffold structure library for rapid prototyping. Part 2: Parametric library and assembly program. Int. J. Adv. Manuf. Technol., 2003, 21(4): 302−312 link1

[12] C. M. Cheah, C. K. Chua, K. F. Leong, C. H. Cheong, M. W. Naing. Automatic algorithm for generating complex polyhedral scaffold structures for tissue engineering. Tissue Eng., 2004, 10(3−4): 595−610 link1

[13] M. W. Naing, C. K. Chua, K. F. Leong, Y. Wang. Fabrication of customised scaffolds using computer-aided design and rapid prototyping techniques. Rapid Prototyping J., 2005, 11(4): 249−259 link1

[14] K. F. Leong, C. K. Chua, N. Sudarmadji, W. Y. Yeong. Engineering functionally graded tissue engineering scaffolds. J. Mech. Behav. Biomed. Mater., 2008, 1(2): 140−152 link1

[15] N. Sudarmadji, C. K. Chua, K. F. Leong. The development of computer-aided system for tissue scaffolds (CASTS) system for functionally graded tissue-engineering scaffolds. Methods Mol. Biol., 2012, 868: 111−123 link1

[16] C. K. Chua, N. Sudarmadji, K. F. Leong, S. M. Chou, S. C. Lim, W. M. Firdaus. Process flow for designing functionally graded tissue engineering scaffolds. In: Innovative Developments in Design and Manufacturing—Advanced Research in Virtual and Rapid Prototyping, 2010: 45−49

[17] C. K. Chua, K. F. Leong, N. Sudarmadji, M. J. J. Liu, S. M. Chou. Selective laser sintering of functionally graded tissue scaffolds. MRS Bull., 2011, 36(12): 1006−1014 link1

[18] S. Cai, J. Xi, C. K. Chua. A novel bone scaffold design approach based on shape function and all-hexahedral mesh refinement. Methods in Molecular Biology, 2012, 868: 45−55 link1

[19] N. Yang, Z. Quan, D. Zhang, Y. Tian. Multi-morphology transition hybridization CAD design of minimal surface porous structures for use in tissue engineering. Comput. Aided Design, 2014, 56: 11−21 link1

[20] J. Rouwkema, N. C. Rivron, C. A. van Blitterswijk. Vascularization in tissue engineering. Trends Biotechnol., 2008, 26(8): 434−441 link1

[21] D. Druecke, Neovascularization of poly(ether ester) block-copolymer scaffolds in vivo: Long-term investigations using intravital fluorescent microscopy. J. Biomed. Mater. Res. A, 2004, 68A(1): 10−18 link1

[22] V. Karageorgiou, D. Kaplan. Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005, 26(27): 5474−5491 link1

[23] M. O. Wang, Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering. Adv. Mater., 2015, 27(1): 138−144 link1

[24] R. Suntornnond, J. An, W. Y. Yeong, C. K. Chua. Hybrid membrane based structure: A novel approach for tissue engineering scaffold. In: The 4th International Conference on Additive Manufacturing and Bio-manufacturing (ICAM-BM 2014). Beijing, China, 2014: 41−42

[25] C. K. Chua, K. F. Leong. 3D Printing and Additive Manufacturing: Principles and Applications. Singapore: World Scientific Publishing Company Pte Limited, 2014

[26] C. W. Yung, L. Q. Wu, J. A. Tullman, G. F. Payne, W. E. Bentley, T. A. Barbari. Transglutaminase crosslinked gelatin as a tissue engineering scaffold. J. Biomed. Mater. Res. A, 2007, 83A(4): 1039−1046 link1

[27] Y. Yan, Direct construction of a three-dimensional structure with cells and hydrogel. J. Bioact. Compat. Pol., 2005, 20(3): 259−269 link1

[28] F. P. Melchels, J. Feijen, D. W. Grijpma. A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography. Biomaterials, 2009, 30(23−24): 3801−3809 link1

[29] J. Y. Tan, C. K. Chua, K. F. Leong. Indirect fabrication of gelatin scaffolds using rapid prototyping technology. Virtual and Physical Prototyping, 2010, 5(1): 45−53 link1

[30] M. J. J. Liu, S. M. Chou, C. K. Chua, B. C. M. Tay, B. K. Ng. The development of silk fibroin scaffolds using an indirect rapid prototyping approach: Morphological analysis and cell growth monitoring by spectral-domain optical coherence tomography. Med. Eng. Phys., 2013, 35(2): 253−262 link1

[31] D. Dean, Multiple initiators and dyes for continuous Digital Light Processing (cDLP) additive manufacture of resorbable bone tissue engineering scaffolds: A new method and new material to fabricate resorbable scaffold for bone tissue engineering via continuous Digital Light Processing. Virtual and Physical Prototyping, 2014, 9(1): 3−9 link1

[32] C. Wu, 3D-printing of highly uniform CaSiO3 ceramic scaffolds: Preparation, characterization and in vivo osteogenesis. J. Mater. Chem., 2012, 22(24): 12288−12295 link1

[33] D. W. Hutmacher, T. Schantz, I. Zein, K. W. Ng, S. H. Teoh, K. C. Tan. Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. J. Biomed. Mater. Res., 2001, 55(2): 203−216 link1

[34] G. Yu, Y. Ding, D. Li, Y. Tang. A low cost cutter-based paper lamination rapid prototyping system. Int. J. Mach. Tools Manuf., 2003, 43(11): 1079−1086 link1

[35] D. Ahn, J. H. Kweon, J. Choi, S. Lee. Quantification of surface roughness of parts processed by laminated object manufacturing. J. Mater. Process. Technol., 2012, 212(2): 339−346 link1

[36] G. S. Kelly, M. S. Jr Just, S. G. Advani, J. W. Gillespie. Energy and bond strength development during ultrasonic consolidation. J. Mater. Process. Technol., 2014, 214(8): 1665−1672 link1

[37] Z. H. Liu, D. Q. Zhang, S. L. Sing, C. K. Chua, L. E. Loh. Interfacial characterization of SLM parts in multi-material processing: Metallurgical diffusion between 316L stainless steel and C18400 copper alloy. Mater. Charact., 2014, 94: 116−125 link1

[38] W. Y. Yeong, Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering. Acta Biomater., 2010, 6(6): 2028−2034 link1

[39] C. Guo, W. Ge, F. Lin. Effects of scanning parameters on material deposition during Electron Beam Selective Melting of Ti-6Al-4V powder. J. Mater. Process. Technol., 2015, 217: 148−157 link1

[40] T. Durejko, M. Ziętala, W. Polkowski, T. Czujko. Thin wall tubes with Fe3Al/SS316L graded structure obtained by using laser engineered net shaping technology. Mater. Des., 2014, 63: 766−774 link1

[41] M. Gharbi, Influence of various process conditions on surface finishes induced by the direct metal deposition laser technique on a Ti-6Al-4V alloy. J. Mater. Process. Technol., 2013, 213(5): 791−800 link1

[42] M. Castilho, Direct 3D powder printing of biphasic calcium phosphate scaffolds for substitution of complex bone defects. Biofabrication, 2014, 6(1): 015006 link1

[43] A. Butscher, Printability of calcium phosphate powders for three-dimensional printing of tissue engineering scaffolds. Acta Biomater., 2012, 8(1): 373−385 link1

[44] A. Butscher, M. Bohner, N. Doebelin, S. Hofmann, R. Müller. New depowdering-friendly designs for three-dimensional printing of calcium phosphate bone substitutes. Acta Biomater., 2013, 9(11): 9149−9158 link1

[45] K. C. Ang, K. F. Leong, C. K. Chua, M. Chandrasekaran. Compressive properties and degradability of poly(ε-caprolatone)/hydroxyapatite composites under accelerated hydrolytic degradation. J. Biomed. Mater. Res. A, 2007, 80A(3): 655−660 link1

[46] C. M. Cheah, K. F. Leong, C. K. Chua, K. H. Low, H. S. Quek. Characterization of microfeatures in selective laser sintered drug delivery devices. Proc. Inst. Mech. Eng. H, 2002, 216(6): 369−383 link1

[47] K. F. Leong, C. K. Chua, W. S. Gui, Verani. Building porous biopolymeric microstructures for controlled drug delivery devices using selective laser sintering. Int. J. Adv. Manuf. Technol., 2006, 31(5−6): 483−489 link1

[48] K. F. Leong, F. E. Wiria, C. K. Chua, S. H. Li. Characterization of a poly-ε-caprolactone polymeric drug delivery device built by selective laser sintering. Biomed Mater Eng., 2007, 17(3): 147−157

[49] K. H. Tan, Selective laser sintering of biocompatible polymers for applications in tissue engineering. Biomed Mater Eng., 2005, 15(1−2): 113−124

[50] R. L. Simpson, Development of a 95/5 poly(L-lactide-co-glycolide)/hydroxylapatite and ε-tricalcium phosphate scaffold as bone replacement material via selective laser sintering. J. Biomed. Mater. Res. B Appl. Biomater., 2008, 84B(1): 17−25 link1

[51] K. H. Tan, Scaffold development using selective laser sintering of polyetheretherketone-hydroxyapatite biocomposite blends. Biomaterials, 2003, 24(18): 3115−3123 link1

[52] K. H. Tan, C. K. Chua, K. F. Leong, M. W. Naing, C. M. Cheah. Fabrication and characterization of three-dimensional poly(ether-ether-ketone)/-hydroxyapatite biocomposite scaffolds using laser sintering. Proc. Inst. Mech. Eng. H, 2005, 219(3): 183−194

[53] C. K. Chua, K. F. Leong, K. H. Tan, F. E. Wiria, C. M. Cheah. Development of tissue scaffolds using selective laser sintering of polyvinyl alcohol/hydroxyapatite biocomposite for craniofacial and joint defects. J. Mater. Sci. Mater. Med., 2004, 15(10): 1113−1121 link1

[54] F. E. Wiria, C. K. Chua, K. F. Leong, Z. Y. Quah, M. Chandrasekaran, M. W. Lee. Improved biocomposite development of poly(vinyl alcohol) and hydroxyapatite for tissue engineering scaffold fabrication using selective laser sintering. J. Mater. Sci. Mater. Med., 2008, 19(3): 989−996 link1

[55] F. E. Wiria, K. F. Leong, C. K. Chua, Y. Liu. Poly-ε-caprolactone/hydroxyapatite for tissue engineering scaffold fabrication via selective laser sintering. Acta Biomater., 2007, 3(1): 1−12 link1

[56] F. E. Wiria, N. Sudarmadji, K. F. Leong, C. K. Chua, E. W. Chng, C. C. Chan. Selective laser sintering adaptation tools for cost effective fabrication of biomedical prototypes. Rapid Prototyping J., 2010, 16(2): 90−99 link1

[57] G. Kim, J. Son, S. Park, W. Kim. Hybrid process for fabricating 3D hierarchical scaffolds combining rapid prototyping and electrospinning. Macromol. Rapid Commun., 2008, 29(19): 1577−1581 link1

[58] S. H. Park, U. H. Koh, M. Kim, D. Y. Yang, K. Y. Suh, J. H. Shin. Hierarchical multilayer assembly of an ordered nanofibrous scaffold via thermal fusion bonding. Biofabrication, 2014, 6(2): 024107 link1

[59] C. H. Chen, V. B. H. Shyu, J. P. Chen, M. Y. Lee. Selective laser sintered poly-ε-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering. Biofabrication, 2014, 6(1): 015004 link1

[60] C. K. Chua, M. W. Naing, K. F. Leong, C. M. Cheah. Novel method for producing polyhedra scaffolds in tissue engineering. In: Virtual Modeling and Rapid Manufacturing—Advanced Research in Virtual and Rapid Prototyping, 2003: 633−640

[61] H. S. Ramanath, C. K. Chua, K. F. Leong, K. D. Shah. Melt flow behaviour of poly-ε-caprolactone in fused deposition modelling. J. Mater. Sci. Mater. Med., 2008, 19(7): 2541−2550 link1

[62] F. E. Wiria, K. F. Leong, C. K. Chua. Modeling of powder particle heat transfer process in selective laser sintering for fabricating tissue engineering scaffolds. Rapid Prototyping J., 2010, 16(6): 400−410 link1

[63] K. C. Ang, K. F. Leong, C. K. Chua, M. Chandrasekaran. Investigation of the mechanical properties and porosity relationships in fused deposition modeling-fabricated porous structures. Rapid Prototyping J., 2006, 12(2): 100−105 link1

[64] H. S. Ramanath, M. Chandrasekaran, C. K. Chua, K. F. Leong, K. D. Shah. Modeling of extrusion behavior of biopolymer and composites in fused deposition modeling. In: Key Engineering Materials, 2007, 334−335: 1241−1244

[65] N. Sudarmadji, J. Y. Tan, K. F. Leong, C. K. Chua, Y. T. Loh. Investigation of the mechanical properties and porosity relationships in selective laser-sintered polyhedral for functionally graded scaffolds. Acta Biomater., 2011, 7(2): 530−537 link1

[66] C. E. Misch, Z. Qu, M. W. Bidez. Mechanical properties of trabecular bone in the human mandible: Implications for dental implant treatment planning and surgical placement. J. Oral Maxillofac. Surg., 1999, 57(6): 700−706, discussion 706−708 link1

[67] C. K. Chua, M. J. J. Liu, S. M. Chou. Additive manufacturing-assisted scaffold-based tissue engineering. In: Innovative Developments in Virtual and Physical Prototyping—Proceedings of the 5th International Conference on Advanced Research and Rapid Prototyping, 2012: 13−21

[68] W. Y. Yeong, C. K. Chua, K. F. Leong, M. Chandrasekaran, M. W. Lee. Indirect fabrication of collagen scaffold based on inkjet printing technique. Rapid Prototyping J., 2006, 12(4): 229−237 link1

[69] W. Y. Yeong, C. K. Chua, K. F. Leong, M. Chandrasekaran, M. W. Lee. Comparison of drying methods in the fabrication of collagen scaffold via indirect rapid prototyping. J. Biomed. Mater. Res. B Appl. Biomater., 2007, 82B(1): 260−266 link1

[70] J. Y. Tan, C. K. Chua, K. F. Leong. Indirect fabrication of tissue engineering scaffolds using rapid prototyping and a foaming process. In: Innovative Developments in Design and Manufacturing—Advanced Research in Virtual and Rapid Prototyping, 2010: 51−57

[71] J. Y. Tan, C. K. Chua, K. F. Leong. Fabrication of channeled scaffolds with ordered array of micro-pores through microsphere leaching and indirect Rapid Prototyping technique. Biomed. Microdevices, 2013, 15(1): 83−96 link1

[72] C. H. Chen, J. M. J. Liu, C. K. Chua, S. M. Chou, V. B. H. Shyu, J. P. Chen. Cartilage tissue engineering with silk fibroin scaffolds fabricated by indirect additive manufacturing technology. Materials (Basel), 2014, 7(3): 2104−2119 link1

[73] V. Mironov, V. Kasyanov, R. R. Markwald. Organ printing: From bioprinter to organ biofabrication line. Curr. Opin. Biotechnol., 2011, 22(5): 667−673 link1

[74] M. Bartnikowski, T. J. Klein, F. P. W. Melchels, M. A. Woodruff. Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures. Biotechnol. Bioeng., 2014, 111(7): 1440−1451 link1

[75] M. Ghaedi, J. J. Mendez, P. F. Bove, A. Sivarapatna, M. S. B. Raredon, L. E. Niklason. Alveolar epithelial differentiation of human induced pluripotent stem cells in a rotating bioreactor. Biomaterials, 2014, 35(2): 699−710 link1

[76] T. W. G. M. Spitters, A dual flow bioreactor with controlled mechanical stimulation for cartilage tissue engineering. Tissue Eng. Part C Methods, 2013, 19(10): 774−783 link1

[77] L. Dan, C. K. Chua, K. F. Leong. Fibroblast response to interstitial flow: A state-of-the-art review. Biotechnol. Bioeng., 2010, 107(1): 1−10 link1

[78] D. Liu, C. K. Chua, K. F. Leong. A mathematical model for fluid shear-sensitive 3D tissue construct development. Biomech. Model. Mechanobiol., 2013, 12(1): 19−31 link1

[79] B. C. M. Tay, C. Y. Fu, B. K. Ng, J. M. J. Liu, S. M. Chou, C. K. Chua. Monitoring cell proliferation in silk fibroin scaffolds using spectroscopic optical coherence tomography. Microw. Opt. Technol. Lett., 2013, 55(11): 2587−2594 link1

[80] C. K. Chua, W. Y. Yeong. Bioprinting: Principles and Applications. Singapore: World Scientific Publishing Company Pte Limited, 2014

[81] V. Mironov, T. Boland, T. Trusk, G. Forgacs, R. R. Markwald. Organ printing: Computer-aided jet-based 3D tissue engineering. Trends Biotechnol., 2003, 21(4): 157−161 link1

[82] V. Mironov, V. Kasyanov, C. Drake, R. R. Markwald. Organ printing: Promises and challenges. Regen. Med., 2008, 3(1): 93−103 link1

[83] V. Mironov, R. P. Visconti, V. Kasyanov, G. Forgacs, C. J. Drake, R. R. Markwald. Organ printing: Tissue spheroids as building blocks. Biomaterials, 2009, 30(12): 2164−2174 link1

[84] J. An, C. K. Chua, T. Yu, H. Li, L. P. Tan. Advanced nanobiomaterial strategies for the development of organized tissue engineering constructs. Nanomedicine (Lond), 2013, 8(4): 591−602 link1

[85] Alec. Russian scientists to unveil 3D bioprinted transplantable organ in March 2015. 2014-11-10. http://www.3ders.org/articles/20141110-russian-scientists-to-unveil-3d-bioprinted-transplantable-organ-in-march-2015.html

[86] S. V. Murphy, A. Atala. 3D bioprinting of tissues and organs. Nat. Biotechnol., 2014, 32(8): 773−785 link1

[87] D. B. Kolesky, R. L. Truby, A. S. Gladman, T. A. Busbee, K. A. Homan, J. A. Lewis. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv. Mater., 2014, 26(19): 3124−3130 link1

[88] N. E. Fedorovich, Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds. Tissue Eng. Part C Methods, 2012, 18(1): 33−44 link1

[89] J. M. Lee, W. Y. Yeong. A preliminary model of time-pressure dispensing system for bioprinting based on printing and material parameters. In: Virtual and Physical Prototyping, 2014: 1−6

[90] C. Cvetkovic, Three-dimensionally printed biological machines powered by skeletal muscle. Proc. Natl. Acad. Sci. U.S.A., 2014, 111(28): 10125−10130 link1

[91] S. Tibbits. 4D printing: Multi-material shape change. Architectural Design, 2014, 84(1): 116−121

[92] Q. Ge, C. K. Dunn, H. J. Qi, M. L. Dunn. Active origami by 4D printing. In: Smart Materials and Structures, 2014, 23: 094007−094022 link1

[93] E. Pei. 4D printing—Revolution or fad? Assembly Automation, 2014, 34(2): 123−127 link1

[94] E. M. Teoh, C. K. Chua, Y. Liu, D. Q. Zhang. Four dimensional (4D) printing using polyjet technology. In: The 4th International Conference on Additive Manufacturing and Bio-manufacturing (ICAM-BM 2014). Beijing, China, 2014: 35−36

[95] R. W. Esmond, G. C. Phero. The additive manufacturing revolution and the corresponding legal landscape. In: Virtual and Physical Prototyping, 2014: 1−4

Related Research