Extrusion-Based Bioprinting

This chapter presents extrusion-based bioprinting (EBB) technology, which has made a substantial progress during the last decade. EBB has great versatility in printing various biologics including cells, tissues, tissue constructs, organ modules, and microfluidic devices in applications from basic research and pharmaceutics to clinics. EBB has great benefits and flexibility in printing a wide range of bioinks including tissue spheroids, tissue strands, cell pellet, microcarriers, decellularized matrix components, and cell-laden hydrogels due to its flexibility in using large nozzles and a wide variety of extrusion mechanisms. This chapter describes EBB technology, its working principle, and the underlying physics behind it, and presents comparison of EBB with respect to other bioprinting modalities, available process configurations, and the bioink materials used in EBB. In addition, current limitations are discussed and future prospects are presented to the reader.

[1]  Dietmar W Hutmacher,et al.  Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. , 2004, Trends in biotechnology.

[2]  C. C. Landry,et al.  Diffusion-based deprotection in mesoporous materials: a strategy for differential functionalization of porous silica particles. , 2007, Journal of the American Chemical Society.

[3]  Lori A. Setton,et al.  Photocrosslinkable Hyaluronan as a Scaffold for Articular Cartilage Repair , 2004, Annals of Biomedical Engineering.

[4]  V. Mironov,et al.  Engineering biological structures of prescribed shape using self-assembling multicellular systems. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Ibrahim T. Ozbolat,et al.  Modeling of Spatially Controlled Biomolecules in Three-Dimensional Porous Alginate Structures , 2010 .

[6]  G. Prestwich,et al.  Dynamically Crosslinked Gold Nanoparticle – Hyaluronan Hydrogels , 2010, Advanced materials.

[7]  Han Tong Loh,et al.  Fabrication of 3D chitosan–hydroxyapatite scaffolds using a robotic dispensing system , 2002 .

[8]  Wei Sun,et al.  Biopolymer deposition for freeform fabrication of hydrogel tissue constructs , 2007 .

[9]  Josep A Planell,et al.  Biofabrication of tissue constructs by 3D bioprinting of cell-laden microcarriers , 2014, Biofabrication.

[10]  Peter Martin,et al.  A review and evaluation of melt temperature sensors for polymer extrusion , 2012 .

[11]  S M Giannitelli,et al.  Current trends in the design of scaffolds for computer-aided tissue engineering. , 2014, Acta biomaterialia.

[12]  Paul Yager,et al.  Diffusion-based analysis of molecular interactions in microfluidic devices , 2004, Proceedings of the IEEE.

[13]  F. Lin,et al.  Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. , 2006, Tissue engineering.

[14]  Margam Chandrasekaran,et al.  Rapid prototyping in tissue engineering: challenges and potential. , 2004, Trends in biotechnology.

[15]  Harrie Weinans,et al.  Sustained Release of BMP-2 in Bioprinted Alginate for Osteogenicity in Mice and Rats , 2013, PloS one.

[16]  Kimberly A. Homan,et al.  Bioprinting: 3D Bioprinting of Vascularized, Heterogeneous Cell‐Laden Tissue Constructs (Adv. Mater. 19/2014) , 2014 .

[17]  Ibrahim T. Ozbolat,et al.  Multi-function Based Modeling of 3D Heterogeneous Wound Scaffolds for Improved Wound Healing , 2010 .

[18]  U. Zimmermann,et al.  In vivo determination of tumor oxygenation during growth and in response to carbogen breathing using 15C5-loaded alginate capsules as fluorine-19 magnetic resonance imaging oxygen sensors. , 2004, International journal of radiation oncology, biology, physics.

[19]  Clément Sanchez,et al.  Synthesis and Characterization of Mesostructured Titania-Based Materials through Evaporation-Induced Self-Assembly , 2002 .

[20]  Alexander Schramm,et al.  Angiogenic and inflammatory response to biodegradable scaffolds in dorsal skinfold chambers of mice. , 2006, Biomaterials.

[21]  Wei Zhu,et al.  Bio-inspired detoxification using 3D-printed hydrogel nanocomposites , 2014, Nature Communications.

[22]  Barbara Rothen-Rutishauser,et al.  Engineering an in vitro air-blood barrier by 3D bioprinting , 2015, Scientific Reports.

[23]  Nupura S. Bhise,et al.  Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels , 2014, Biofabrication.

[24]  Ibrahim T. Ozbolat,et al.  Direct Bioprinting of Vessel-Like Tubular Microfluidic Channels , 2013 .

[25]  Wei Sun,et al.  Multi‐nozzle deposition for construction of 3D biopolymer tissue scaffolds , 2005 .

[26]  James J. Yoo,et al.  Bioprinted Amniotic Fluid‐Derived Stem Cells Accelerate Healing of Large Skin Wounds , 2012, Stem cells translational medicine.

[27]  Stuart K Williams,et al.  Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[28]  Neri Oxman,et al.  Water-Based Robotic Fabrication: Large-Scale Additive Manufacturing of Functionally Graded Hydrogel Composites via Multichamber Extrusion , 2014 .

[29]  Adam S. Hayward,et al.  Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME , 2013, Archives of Toxicology.

[30]  Yen Wei,et al.  Electrospinning polyaniline-contained gelatin nanofibers for tissue engineering applications. , 2006, Biomaterials.

[31]  I. Zein,et al.  Fused deposition modeling of novel scaffold architectures for tissue engineering applications. , 2002, Biomaterials.

[32]  F. Lin,et al.  Rapid Prototyping Three-Dimensional Cell/Gelatin/Fibrinogen Constructs for Medical Regeneration: , 2007 .

[33]  Seung-Schik Yoo,et al.  Generation of Multi-scale Vascular Network System Within 3D Hydrogel Using 3D Bio-printing Technology , 2014, Cellular and molecular bioengineering.

[34]  Nan Ma,et al.  Laser printing of skin cells and human stem cells. , 2010, Tissue engineering. Part C, Methods.

[35]  Karl R Edminster,et al.  Multi-layered culture of human skin fibroblasts and keratinocytes through three-dimensional freeform fabrication. , 2009, Biomaterials.

[36]  Vijay Kumar Sharma,et al.  Coaxial electrohydrodynamic atomization: microparticles for drug delivery applications. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[37]  B. Duan,et al.  3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. , 2013, Journal of biomedical materials research. Part A.

[38]  Ibrahim T. Ozbolat,et al.  Bioprinting Technology: A Current State-of-the-Art Review , 2014 .

[39]  Vladimir Mironov,et al.  Organ printing: computer-aided jet-based 3D tissue engineering. , 2003, Trends in biotechnology.

[40]  Pankaj Karande,et al.  Design and fabrication of human skin by three-dimensional bioprinting. , 2014, Tissue engineering. Part C, Methods.

[41]  Vladimir Mironov,et al.  Organ printing: tissue spheroids as building blocks. , 2009, Biomaterials.

[42]  J T Czernuszka,et al.  Novel 3D collagen scaffolds fabricated by indirect printing technique for tissue engineering. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[43]  Suwan N Jayasinghe,et al.  Electrohydrodynamic jetting of mouse neuronal cells. , 2006, The Biochemical journal.

[44]  K H Kang,et al.  Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds , 2012, Biofabrication.

[45]  Ibrahim T. Ozbolat,et al.  A Hybrid Bioprinting Approach for Scale-Up Tissue Fabrication , 2014 .

[46]  T. Q. Huang,et al.  3D printing of biomimetic microstructures for cancer cell migration , 2014, Biomedical microdevices.

[47]  Ibrahim T. Ozbolat,et al.  Bioprinting scale-up tissue and organ constructs for transplantation. , 2015, Trends in biotechnology.

[48]  Ying Mei,et al.  3D printing facilitated scaffold-free tissue unit fabrication , 2014, Biofabrication.

[49]  M. Rinaudo,et al.  Chitin and chitosan: Properties and applications , 2006 .

[50]  R. Landers,et al.  Biofunctional rapid prototyping for tissue‐engineering applications: 3D bioplotting versus 3D printing , 2004 .

[51]  W. Sun,et al.  Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug conversion in a dual-tissue microfluidic chip , 2011, Biofabrication.

[52]  F. Guillemot,et al.  Bioprinting by laser-induced forward transfer for tissue engineering applications: jet formation modeling , 2010, Biofabrication.

[53]  Stuart K Williams,et al.  Three-dimensional bioassembly tool for generating viable tissue-engineered constructs. , 2004, Tissue engineering.

[54]  Susan C. Roberts,et al.  Pluronic F127 as a cell encapsulation material: utilization of membrane-stabilizing agents. , 2005, Tissue engineering.

[55]  D. Cho,et al.  3D printing of composite tissue with complex shape applied to ear regeneration , 2014, Biofabrication.

[56]  P. Dubruel,et al.  The 3D printing of gelatin methacrylamide cell-laden tissue-engineered constructs with high cell viability. , 2014, Biomaterials.

[57]  Ibrahim T. Ozbolat,et al.  Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink , 2016, Scientific Reports.

[58]  Wouter J A Dhert,et al.  Distinct tissue formation by heterogeneous printing of osteo- and endothelial progenitor cells. , 2011, Tissue engineering. Part A.

[59]  Wei Sun,et al.  Bioprinting endothelial cells with alginate for 3D tissue constructs. , 2009, Journal of biomechanical engineering.

[60]  Ibrahim T. Ozbolat,et al.  Tissue strands as “bioink” for scale-up organ printing , 2014, 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[61]  G. Whitesides,et al.  Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in paper. , 2008, Analytical chemistry.

[62]  Rocky S Tuan,et al.  Application of visible light-based projection stereolithography for live cell-scaffold fabrication with designed architecture. , 2013, Biomaterials.

[63]  P. Gatenholm,et al.  3D Bioprinting Human Chondrocytes with Nanocellulose-Alginate Bioink for Cartilage Tissue Engineering Applications. , 2015, Biomacromolecules.

[64]  L. Niklason,et al.  Scaffold-free vascular tissue engineering using bioprinting. , 2009, Biomaterials.

[65]  Ibrahim T. Ozbolat,et al.  Evaluation of cell viability and functionality in vessel-like bioprintable cell-laden tubular channels. , 2013, Journal of biomechanical engineering.

[66]  G. Weir,et al.  Core–Shell Hydrogel Microcapsules for Improved Islets Encapsulation , 2013, Advanced healthcare materials.

[67]  Ibrahim T. Ozbolat,et al.  Development of 'Multi-arm Bioprinter' for hybrid biofabrication of tissue engineering constructs , 2014 .

[68]  Hod Lipson,et al.  Additive manufacturing for in situ repair of osteochondral defects , 2010, Biofabrication.

[69]  J. Malda,et al.  Development and characterisation of a new bioink for additive tissue manufacturing. , 2014, Journal of materials chemistry. B.

[70]  J. Perkins,et al.  Are we reporting the same thing? , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[71]  Amir Faghri,et al.  Transport Phenomena in Multiphase Systems , 2006 .

[72]  Ryan B. Wicker,et al.  Laser curing of silver-based conductive inks for in situ 3D structural electronics fabrication in stereolithography , 2014 .

[73]  V Mironov,et al.  Scalable robotic biofabrication of tissue spheroids , 2011, Biofabrication.

[74]  D W Hutmacher,et al.  Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2. , 2005, Biomaterials.

[75]  G. Prestwich,et al.  Photocrosslinkable hyaluronan-gelatin hydrogels for two-step bioprinting. , 2010, Tissue engineering. Part A.

[76]  D. Weaire,et al.  The optimal tap: three-dimensional nozzle design , 2005 .

[77]  D. Odde,et al.  Laser-guided direct writing of living cells. , 2000, Biotechnology and bioengineering.

[78]  S. Yoo,et al.  On‐demand three‐dimensional freeform fabrication of multi‐layered hydrogel scaffold with fluidic channels , 2010, Biotechnology and bioengineering.

[79]  U. Demirci,et al.  Single cell epitaxy by acoustic picolitre droplets. , 2007, Lab on a chip.

[80]  J. Lewis,et al.  Omnidirectional Printing of 3D Microvascular Networks , 2011, Advanced materials.

[81]  N. Kikuchi,et al.  A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity. , 2004, Journal of biomechanics.

[82]  Melba Navarro,et al.  Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte/macrophage responses: unraveling the effect of 3-D structures on inflammation. , 2014, Acta biomaterialia.

[83]  D. Odde,et al.  Laser-guided direct writing for applications in biotechnology. , 1999, Trends in biotechnology.

[84]  Ventola Cl.  Medical Applications for 3D Printing: Current and Projected Uses. , 2014 .

[85]  Joon Hyung Park,et al.  Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels , 2015, Science Advances.

[86]  Dong Liang,et al.  A Low-Cost, Normally Closed, Solenoid Valve for Non-Contact Dispensing in the Sub-µL Range , 2013, Micromachines.

[87]  Anthony Atala,et al.  Evaluation of hydrogels for bio-printing applications. , 2013, Journal of biomedical materials research. Part A.

[88]  Alessandro Tocchio,et al.  Versatile fabrication of vascularizable scaffolds for large tissue engineering in bioreactor. , 2015, Biomaterials.

[89]  P. Rajagopalan,et al.  3D Hepatic Cultures Simultaneously Maintain Primary Hepatocyte and Liver Sinusoidal Endothelial Cell Phenotypes , 2010, PloS one.

[90]  F. Marga,et al.  Toward engineering functional organ modules by additive manufacturing , 2012, Biofabrication.

[91]  T. Boland,et al.  Cell and organ printing 2: fusion of cell aggregates in three-dimensional gels. , 2003, The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.

[92]  Scott J Hollister,et al.  Combined use of designed scaffolds and adenoviral gene therapy for skeletal tissue engineering. , 2006, Biomaterials.

[93]  Jong-Hwan Lee,et al.  Three-dimensional bioprinting of rat embryonic neural cells , 2009, Neuroreport.

[94]  Hod Lipson,et al.  Fabricated: The New World of 3D Printing , 2013 .

[95]  James J. Yoo,et al.  Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. , 2013, Biomaterials.

[96]  Anthony Atala,et al.  Biomaterials for Integration with 3-D Bioprinting , 2014, Annals of Biomedical Engineering.

[97]  Alessandro Giacomello,et al.  Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells. , 2012, Biomaterials.

[98]  D. Cho,et al.  Biomimetic 3D tissue printing for soft tissue regeneration. , 2015, Biomaterials.

[99]  Zhongmin Jin,et al.  Cartilage Repair and Subchondral Bone Migration Using 3D Printing Osteochondral Composites: A One-Year-Period Study in Rabbit Trochlea , 2014, BioMed research international.

[100]  E. Saiz,et al.  Direct write assembly of calcium phosphate scaffolds using a water-based hydrogel. , 2010, Acta biomaterialia.

[101]  Jos Malda,et al.  Biofabrication of osteochondral tissue equivalents by printing topologically defined, cell-laden hydrogel scaffolds. , 2012, Tissue engineering. Part C, Methods.

[102]  Thomas Boland,et al.  Characterization of Patterned Self-Assembled Monolayers and Protein Arrays Generated by the Ink-Jet Method† , 2003 .

[103]  Younan Xia,et al.  Electrospinning Nanofibers as Uniaxially Aligned Arrays and Layer‐by‐Layer Stacked Films , 2004 .

[104]  Peter F. M. Choong,et al.  Chondrogenesis of Infrapatellar Fat Pad Derived Adipose Stem Cells in 3D Printed Chitosan Scaffold , 2014, PloS one.

[105]  W. Dhert,et al.  Three-dimensional fiber deposition of cell-laden, viable, patterned constructs for bone tissue printing. , 2008, Tissue engineering. Part A.

[106]  Gabor Forgacs,et al.  Biofabrication and testing of a fully cellular nerve graft , 2013, Biofabrication.

[107]  Johnson H. Y. Chung,et al.  Bio-ink properties and printability for extrusion printing living cells. , 2013, Biomaterials science.

[108]  J. Vacanti,et al.  A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. , 2003, Biomaterials.

[109]  Karoly Jakab,et al.  Tissue engineering by self-assembly and bio-printing of living cells , 2010, Biofabrication.

[110]  Ibrahim T. Ozbolat,et al.  Microfabrication of scaffold-free tissue strands for three-dimensional tissue engineering , 2015, Biofabrication.

[111]  Jiwei Huang,et al.  Coaxial electrospray of microparticles and nanoparticles for biomedical applications , 2012, Expert review of medical devices.

[112]  Anthony Atala,et al.  3D bioprinting of tissues and organs , 2014, Nature Biotechnology.

[113]  Yong He,et al.  Fabrication of low cost soft tissue prostheses with the desktop 3D printer , 2014, Scientific Reports.

[114]  GasperiniLuca,et al.  An electrohydrodynamic bioprinter for alginate hydrogels containing living cells. , 2015 .

[115]  J. Lewis,et al.  3D Bioprinting of Vascularized, Heterogeneous Cell‐Laden Tissue Constructs , 2014, Advanced materials.