3D Bioprinting from Lab to Industry E-Book
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- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Sprache: Englisch
A complete overview of bioprinting, from fundamentals and essential topics to recent advances and future applications
Additive manufacturing, also known as 3D printing, is one of the most transformative technological processes to emerge in recent decades. Its layer-by-layer construction method can create objects to remarkably precise specifications with minimal waste or energy consumption. Bioprinting, a related process that employs cells and biomaterials instead of man-made substances or industrial materials, has a range of biomedical and chemical uses that make it an exciting and fast-growing area of research.
3D Bioprinting from Lab to Industry offers a cutting-edge overview of this topic, its recent advances, and its future applications. Taking an interdisciplinary approach to a flourishing research field, this book exceeds all existing treatments of the subject in its scope and comprehensiveness. Moving from fundamental principles of the technology to its immense future potential, this is a must-own volume for scientists looking to incorporate this process into their research or product development.
3D Bioprinting from Lab to Industry readers will also find:
- Treatment of printing parameters, surface topography requirements, and much more
- Detailed discussion of topics including 5D printing in the medical field, dynamic tuning, the multi-material extrusion approach, and many others
- A complete account of the bioprinting process, from lab requirements to commercialization
3D Bioprinting from Lab to Industry is ideal for researchers—graduate and post-doctoral scholars—in the areas of materials science, biomedical engineering, chemical engineering, biotechnology, and biochemistry.
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Seitenzahl: 936
Veröffentlichungsjahr: 2024
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Table of Contents
Cover
Table of Contents
Title Page
Copyright Page
List of Contributors
Foreword
1 Introduction of 3D Printing and Different Bioprinting Methods
1.1 Introduction of 3D Printing: Principles and Utility
1.2 Ink Preparation and Printability
1.3 Methods of Bioprinting in Fabrication and Tissue Engineering
1.4 Scaffold Modeling and G Coding
1.5 Applications and Utility in Large‐Scale Manufacturing
1.6 Complications and Troubleshooting
References
2 Cellular Requirements and Preparation for Bioprinting
2.1 Introduction
2.2 Types of Bioprinting
2.3 Features Required for Bioprinting with Cells
2.4 Bioprinting Methodologies for Cell Expansion and Proliferation
2.5 The Impact of Bioprinting Process Conditions on Phenotype Alterations
2.6 Discussion
2.7 Conclusion
2.8 Future Prospects
References
3 3D Bioprinting: Materials for Bioprinting Bioinks Selection
3.1 Introduction
3.2 Bioprinting Materials
3.3 Bioinks Selectivity Guide
3.4 Classification of Bioprinting Materials
3.5 3D Bioprinting Methods According to the Type of the Bioinks
3.6 Bioinks Selection According to Biomedical Application
3.7 Multicomponent Bioinks
3.8 Future Prospects
References
4 Printed Scaffolds in Tissue Engineering
4.1 Introduction
4.2 Biomedical Application of 3D Printing
4.3 Tissue Engineering: Emerging Applications by 3D Printing
4.4 Conclusions
References
5 Printability and Shape Fidelity in Different Bioprinting Processes
5.1 Introduction
5.2 Fundamentals of Printability
5.3 Bioprinting Techniques and Printability
5.4 Shape Fidelity
5.5 Case Studies and Applications
5.6 Conclusion
References
6 Advancements in Bioprinting for Medical Applications
6.1 Introduction
6.2 Bioprinting for Drug Development and Testing
6.3 Bioprinting in Tissue Engineering, Regenerative Medicine, and Organ Transplantation
6.4 Bioprinting in Tissue: Challenges, Barriers to Clinical Translation, and Future Directions
6.5 Conclusions
Acknowledgments
References
7 4D‐Printed, Smart, Multiresponsive Structures and Their Applications
7.1 Introduction
7.2 4D‐Printing Technologies
7.3 Biomaterials for 4D Bioprinting
7.4 Biomedical Applications for 4D Bioprinting
7.5 Future Perspectives
References
8 Toxicity Aspects and Ethical Issues of Bioprinting
8.1 Introduction
8.2 Toxicity Issues in Bioprinting
8.3 Ethical Issues in Bioprinting
8.4 Issues in Clinical Trials
8.5 Legal Issues in Bioprinting
8.6 Conclusion
References
9 Planning Bioprinting Project
9.1 Introduction
9.2 Background: Image Capturing and Solid Model Preparation of Virtual Anatomical Model for 3D Printing
9.3 Conclusion
References
10 Computational Engineering for 3D Bioprinting: Models, Methods, and Emerging Technologies
10.1 Introduction
10.2 Fundamentals of Numerical Methods in Bioprinting
10.3 Application of Machine Learning for 3D Bioprinting
10.4 Summary
References
11 Controlling Factors of Bioprinting
11.1 Introduction
11.2 Factors Influencing the Printability of Hydrogel Bioink
11.3 Bioink Formulation
11.4 Influence of Printing Process on Cell Behavior
11.5 Importance of Patterning and Surface Topography
11.6 Contact Guidance and Directional Growth of Cells
11.7 Cell Viability and Mitigation Process
11.8 Possible Mitigation Techniques
11.9 Conclusion
References
12 In Situ Bioprinting
12.1 Introduction
12.2 Advantages of In Situ Bioprinting
12.3 In Situ Bioprinting Technologies
12.4 Bioinks and Biomaterials for In Situ Bioprinting
12.5 In Situ Approaches for Tissue Regeneration
12.6 Future Directions
12.7 Conclusion
Acknowledgments
References
13 Importance of Machine Learning in 3D Bioprinting
13.1 Introduction
13.2 3D Bioprinting
13.3 Machine Learning in 3D Bioprinting
13.4 Challenges in 3D Bioprinting Process Using ML
13.5 Future Outlook
13.6 Summary and Conclusion
References
14 Advanced Bioprinting for the Future
14.1 Introduction
14.2 Electrospinning and Bioprinting
14.3 4D Printing
14.4 5D and 6D Printing
14.5 Organ Printing
14.6 Vascularized Organ on a Chip
14.7 Multimaterial Bioprinting
14.8 Printing in Microgravity
14.9 In Vivo Bioprinting
14.10 Biohybrid Robots
14.11 Conclusion and Future Perspectives
References
15 Nanomaterials for Designing Functional Properties of Bioinks
15.1 3D‐Bioprinting
15.2 Designing Functional Bioinks Using Nanoscale Biomaterials
15.3 Synthesis and Tailoring the Properties of Nanobioinks
15.4 Nanobioinks and Tissue Engineering
15.5 Future Outlook
References
16 3D Bioprinting from Lab to Industry
16.1 Introduction
16.2 3D Bioprinting and Its Historical Point of View
16.3 Potential of 3D Bioprinting from Lab to Industry
16.4 The Diversity of 3D Bioprinting
16.5 3D Bioprinting and Human Hearts
16.6 3D Bioprinting and Microfluidic Organ‐on‐a‐Chip Models
16.7 Future Developments
References
Index
End User License Agreement
List of Tables
Chapter 1
Table 1.1 Comparison between the different methodologies of 3DP – laser‐base...
Table 1.2 Comparison of different modes of droplet‐based printing techniques...
Chapter 2
Table 2.1 Some techniques for sterilization and disinfection.
Table 2.2 Mechanotransduction cues caused by different factors and their im...
Chapter 3
Table 3.1 The benefits and drawbacks of 3D bioprinting techniques.
Chapter 4
Table 4.1 Method, specifications, and materials for different 3D printing t...
Table 4.2 3D printing techniques, materials used, and their biomedical appl...
Table 4.3 Targeted drug, technique used, scaffold material, and its biomedi...
Table 4.4 Scaffold materials and properties for tissue engineering applicat...
Chapter 9
Table 9.1 Summary of nearly all common smoothing algorithms use in segmenta...
Table 9.2 Program‐specific user intervention level at different workflow ste...
Table 9.3 Resemblance between medical imaging techniques for regenerative m...
Table 9.4 Comparison of blueprint modeling methods worked in tissue constru...
Table 9.5 A comparison of bioprinting methods. The table is a composite of ...
Chapter 10
Table 10.1 Models for bioink extrusion in fluid mechanics.
Table 10.2 Solid mechanics models for bioprinted constructs.
Table 10.3 ML advancements in bioprinting: techniques and key findings.
Chapter 11
Table 11.1 Major stress factors affecting cell viability in different 3D pr...
Chapter 13
Table 13.1 Summary of common materials in 3D bioprinting.
Table 13.2 Summary of the most recent studies on bioinks.
Chapter 14
Table 14.1 Different categories of stimulus with application and respective...
Table 14.2 Advantages and disadvantages of donated and 3D‐printed organs.
List of Illustrations
Chapter 1
Figure 1.1 Schematic representation of types of 3D bioprinting [21] – extrus...
Figure 1.2 (a) Basic schematic of laser‐assisted printing (b) laser‐guided d...
Figure 1.3 Extrusion printing principles. (a) Basic schematic of extrusion p...
Figure 1.4 Schematic representation of aerosol jet printer with pneumatic an...
Figure 1.5 (a) Schematic representation of electrohydrodynamic jet printing ...
Figure 1.6 (a) Schematic representation of CIJ inkjet printing mechanism, (b...
Figure 1.7 Schematic showing SLA based on (a) digital light processing and (...
Chapter 2
Figure 2.1 Potential of bioprinting different organs.
Figure 2.2 Types of bioprinting.
Figure 2.3 Some of the parameters associated with viable 3D bioprinting.
Figure 2.4 Different classifications of polymers.
Figure 2.5 Development of organs from the 3D bioprinting process.
Figure 2.6 Bioprinted PLA applied with PAMAM (showing fluorescence) and embe...
Figure 2.7 Mechanism of ECM remodeling during cancer. (a) denotes the proces...
Chapter 3
Figure 3.1 The characteristics of standard bioinks.
Figure 3.2 Components and applications of bioprinting materials in the biome...
Figure 3.3 Different types of 3D bioprinted scaffold from different sources ...
Chapter 4
Figure 4.1 Types of 3D printing (a) binder jetting (b) directed energy depos...
Figure 4.2 Photo of the 3D printed scaffolds (1 cm is denoted by scale bar)....
Figure 4.3 In vitro release of insulin through porcine skin from (a) pyramid...
Figure 4.4 Applications of 3D printed devices (a) Valves used to convert the...
Figure 4.5 Fabricating channel embedded elastic gloves and texturing glove s...
Figure 4.6 (a) images of 3D printed scaffold (i) 8% (ii) 10% (iii) 12% (w/v)...
Figure 4.7 (a) resin mold of chitosan–gelatin scaffold and scaffold with hep...
Figure 4.8 (a) Optical images of 3D printed PGS‐zein constructs after crossl...
Chapter 5
Figure 5.1 Shows bioprinting using extrusion and lithography: key aspects to...
Figure 5.2 (a) extrusion‐based bioprinting system, (b) bottom‐up method in a...
Figure 5.3 Diagrammatic classification of INKJET printing system [11].
Figure 5.4 Schematic representation of stereolithography bioprinting system....
Figure 5.5 Quantitative examinations are conducted to evaluate the accuracy ...
Figure 5.6 CT and OCT are utilized to visualize filaments and pore structure...
Chapter 6
Figure 6.1 Sacrificial bioprinting. Sacrificial bioprinting can be used to p...
Figure 6.2 Overview of 3D bioprinting process of 3D scaffolds (right) and co...
Figure 6.3 (a) Applications of 3D bioprinting in skin tissue engineering (b)...
Figure 6.4 Printing of cartilage constructs with various densities using a s...
Figure 6.5 Schematic presentation of the study design and scaffold construct...
Figure 6.6 Using inkjet bioprinting to manufacture alveolar barrier models. ...
Figure 6.7 Development of an in vitro bladder model system. A bladder‐specif...
Chapter 7
Figure 7.1 Schematics of common 4D‐printing technologies. (a) Extrusion‐base...
Figure 7.2 Schematics of the 4D‐printed structure fabricated by water‐respon...
Figure 7.3 Schematics of the 4D‐printed structure fabricated by temperature‐...
Figure 7.4 (a) Schematics of the fabrication of the accordion‐shaped actuato...
Figure 7.5 Schematic representation of different types of stimuli and respon...
Figure 7.6 High‐dimensional printing.
Chapter 8
Figure 8.1 ELSA framework for 3D bioprinting [11].
Figure 8.2 Schematic diagram showing the pathways and protocols followed to ...
Chapter 9
Figure 9.1 Basic workflow for dealing out the patient image volume into 3D p...
Figure 9.2 Meshing fundamentals: (a) solid mesh of mandible through key mesh...
Figure 9.3 (a–c) Segmentation of an aorta from a spine process based on regi...
Figure 9.4 Surface extraction pipeline, cuts roughly into a voxel level and ...
Figure 9.5 (a) Top view of cell aggregates (black) and their support materia...
Figure 9.6 Toolpath preparation at Cartesian coordinates: (a) toolpath outli...
Figure 9.7 Designing a toolpath in parametric coordinates. (a,b) A toolpath ...
Figure 9.8 A graphical presentation of extrusion bioprinting of stem cells. ...
Figure 9.9 A graphical presentation of inkjet bioprinting of stem cell. Drop...
Figure 9.10 A representation of laser‐assisted bioprinting of cells. The las...
Chapter 10
Figure 10.1 Illustration of the sequential workflow in 3D bioprinting for bi...
Figure 10.2 Types of 3D bioprinting.
Figure 10.3 The potential of 3D bioprinting technologies for producing 3D or...
Figure 10.4 Numerical methods and simulations in 3D bioprinting.
Figure 10.5 Sequential stages involved in implementing computational enginee...
Chapter 11
Figure 11.1 Key properties required for 3D extrusion printing of polymers....
Figure 11.2 Schematic illustration of the velocity and shear stress distribu...
Figure 11.3 (a) Consequences of the size of the pore by patterning on cell g...
Figure 11.4 Schematic diagram of the effect of different 2D surface features...
Figure 11.5 Link between surface roughness and cell behavior. Increased cell...
Figure 11.6 Different 2D topographic cues. (a) Uniform straight line; (b) mu...
Figure 11.7 Schematic diagrams of typical 3D scaffolds for cell culture. (a)...
Figure 11.8 Schematic diagrams of representative 3D scaffolds for cell cultu...
Chapter 12
Figure 12.1 In situ bioprinting platforms and innovative methods of additive...
Figure 12.2 Kinematic configurations of different degree of freedom (DoF) sy...
Figure 12.3 (a) Underfilling (underfilled area demonstrated by the encircled...
Figure 12.4
Schematic diagram of a 3D bioprinter end effector, mounted on an
...
Figure 12.5
4D bioprinting approaches
. Bioprint droplets that contain antibi...
Chapter 13
Figure 13.1 Formation of bioinks and their medical applications.
Figure 13.2 Flowchart of the 3D bioprinting techniques.
Figure 13.3 Representing the way to apply NN for optimization purposes in 3D...
Chapter 14
Figure 14.1 Pictorial representation of 5D printing.
Figure 14.2 Contribution of different dimensions in 6D printing.
Figure 14.3 Flexibility of 4D‐ and 6D‐printed models.
Figure 14.4 Lung‐on‐a‐chip model design and fabrication. (a) A schematic rep...
Figure 14.5 Combination of microfluidic multimaterial printing.
Figure 14.6 Multiple axis bioprinting process.
Figure 14.7 Multiscale biohybridization.
Chapter 15
Figure 15.1 Desirable Properties of Bioinks.
Figure 15.2 An illustration of various types of nano‐biomaterials used in bi...
Figure 15.3 A smart multifunctional drug‐loaded nanoparticle is a representa...
Figure 15.4 Designing functional features for nanocomposite bioinks with nan...
Chapter 16
Figure 16.1 Progress and potential of 3D bioprinting from lab to industry.
Figure 16.2 A brief timeline of the development of microfluidic organ‐on‐a‐c...
Guide
Cover Page
Table of Contents
Title Page
Copyright Page
List of Contributors
Foreword
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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3D Bioprinting from Lab to Industry
Edited by
Prosenjit Saha
JIS UniversityKolkata, India
Sabu Thomas
Mahatma Gandhi UniversityKottayam, India
Jinku Kim
Hongik UniversitySejong, Republic of Korea
Manojit Ghosh
Indian Institute of Engineering Science and Technology (IIEST)Howrah, India
Copyright © 2024 by John Wiley & Sons, Inc. All rights reserved, including rights for text and data mining and training of artificial intelligence technologies or similar technologies.
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List of Contributors
Jaideep AdhikariSchool of Advanced MaterialsGreen Energy and Sensor SystemsIndian Institute of EngineeringScience and TechnologyHowrah, West BengalIndia
Noura Al HashimiThe Vijay Lab, Division of EngineeringNew York University Abu DhabiAbu DhabiUAE
Ananya BaruiCentre for Healthcare Science andTechnologyIndian Institute of EngineeringScience and TechnologyShibpurIndia
Hanan H. BehereiRefractories, Ceramics and BuildingMaterials Department, AdvancedMaterialsTechnology and Mineral ResourcesResearch Institute, NationalResearch CentreCairoEgypt
Soumyadeep BeraCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Asmita BiswasSchool of Medical Science andTechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Hema BoraSchool of Medical Science andTechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Shalini DasguptaCentre for Healthcare Science andTechnologyIndian Institute of EngineeringScience and TechnologyShibpurIndia
Anish DebCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Ankita DebCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Poonam DebnathCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Santanu DharaSchool of Medical Science andTechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Krishna DixitSchool of Medical Science andTechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Mohamed G. FarahatBotany and Microbiology Department,Faculty of ScienceCairo UniversityGizaEgypt
Manojit GhoshDepartment of Metallurgy andMaterials EngineeringIndian Institute of EngineeringScience and TechnologyShibpur, West BengalIndia
Laura K. GorwillDepartment of BiologyUniversity of Toronto MississaugaMississauga, OntarioCanada
D. A. GouripriyaCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Yves GrohensLaboratoire d'Ingénierie des Matériauxde BretagneUniversité Bretagne SudLorientFrance
Laila HusseinRefractories, Ceramics and BuildingMaterials Department,Advanced Materials, Technology andMineral Resources Research Institute,National Research CentreCairoEgypt
Varnit JainDepartment of Metallurgy andMaterials EngineeringIndian Institute of EngineeringScience and TechnologyShibpur, West BengalIndia
Maxine Joly‐ChevrierFaculty of MedicineUniversity of MontrealMontreal, QuebecCanada
Josmin P. JoseMar Thoma CollegeTiruvalla, KeralaIndia
Nandakumar KalarikkalInternational and Inter UniversityCentre for Nanoscience andNanotechnologyMahatma Gandhi UniversityKottayam, KeralaIndia
School of Pure and Applied PhysicsMahatma Gandhi UniversityKottayam, KeralaIndia
Ananda KalevarDepartment of Surgery, Division ofOphthalmologyUniversity of SherbrookeSherbrooke, QuebecCanada
Michèle KanhonouLéonard de Vinci Pôle UniversitaireResearch CenterParis La DéfenseFrance
Sofiane KhelladiArts et Métiers Institute of Technology,CNAM, LIFSEHESAM UniversityParisFrance
Jinku KimDepartment of Biological andChemical EngineeringHongik UniversitySejongRepublic of Korea
Vidyapati KumarDepartment of MechanicalEngineeringIndian Institute of TechnologyKharagpur West BengalIndia
Mostafa MabroukRefractories, Ceramics and BuildingMaterials DepartmentAdvanced Materials, Technology andMineral Resources Research Institute,National Research CentreCairoEgypt
Michael MarchandDepartment of Surgery, Division ofOphthalmologyUniversity of SherbrookeSherbrooke, QuebecCanada
Mina MinaDepartment of Mechanical andManufacturing EngineeringUniversity of CalgaryCalgary, AlbertaCanada
Ankita MistriDepartment of MechanicalEngineeringIndian Institute of TechnologyDhanbad, JharkhandIndia
Mona MoanessRefractories, Ceramics and BuildingMaterials DepartmentAdvanced Materials, Technology andMineral Resources Research InstituteNational Research CentreCairoEgypt
Prajisha PrabhakarInternational and Inter UniversityCentre for Nanoscience andNanotechnologyMahatma Gandhi University KottayamKottayam, KeralaIndia
Baisakhee SahaSchool of Medical Science and TechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Prosenjit SahaCentre for Interdisciplinary SciencesJIS Institute of Advance Studies andResearchKolkata, West BengalIndia
Samanta SamSchool of Energy MaterialsMahatma Gandhi UniversityKottayam, KeralaIndia
Debashis SarkarME DepartmentAsansol Engineering CollegeAsansol, West BengalIndia
Aiswarya SathianInternational and Inter UniversityCentre for Nanoscience andNanotechnologyMahatma Gandhi University KottayamKottayam, KeralaIndia
College of Science and EngineeringJames Cook UniversityTownsville, QueenslandAustralia
Vriti SharmaCentre for Healthcare Science andTechnologyIndian Institute of EngineeringScience and TechnologyShibpurIndia
Mridula SreedharanInternational and Inter UniversityCentre for Nanoscience andNanotechnologyMahatma Gandhi UniversityKottayam, KeralaIndia
M.S. SreekalaSchool of Chemical SciencesMahatma Gandhi UniversityKottayam, KeralaIndia
Abbas TcharkhtchiArts et Métiers Institute of TechnologyCNRS, CNAM, PIMMHESAM UniversityParisFrance
Sabu ThomasSchool of Energy MaterialsSchool of Nanoscience andNanotechnologySchool of Polymer Science andTechnologySchool of Chemical Science andInternational and Inter UniversityCentre for Nanoscience andTechnology (IIUCNN)Mahatma Gandhi UniversityKottayam, KeralaIndia
Department of Chemical SciencesUniversity of JohannesburgDoornfontein, JohannesburgSouth Africa
TrEST Research Park, SreekariyamTrivandrum, KeralaIndia
Thara TomMar Thoma CollegeTiruvalla, KeralaIndia
School of Chemical SciencesMahatma Gandhi UniversityKottayam, KeralaIndia
Simon D. TranFaculty of Dental Medicine and OralHealth SciencesMcGill UniversityMontreal, QuebecCanada
Hamid Reza VanaeiLéonard de Vinci Pôle UniversitaireResearch CenterParis La DéfenseFrance
Arts et Métiers Institute of TechnologyCNAM, LIFSEHESAM UniversityParisFrance
Saeedeh VanaeiDepartment of Mechanical Industrialand Manufacturing EngineeringUniversity of ToledoToledo, OHUSA
Shohreh VanaeiDepartment of BioengineeringNortheastern UniversityBoston, MAUSA
Pravin Vasudeo VaidyaSchool of Medical Science andTechnologyIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Advanced TechnologyDevelopment CentreIndian Institute of TechnologyKharagpurKharagpur, West BengalIndia
Sanjairaj VijayavenkataramanThe Vijay Lab, Division of EngineeringNew York University Abu DhabiAbu DhabiUAE
Department of Mechanical andAerospace Engineering, TandonSchool of EngineeringNew York UniversityBrooklyn, NYUSA
Kevin Y. WuDepartment of Surgery, Division ofOphthalmologyUniversity of SherbrookeSherbrooke, QuebecCanada
Foreword
Ajoy Kumar Ray
JIS Institute of Advanced Studies and Research (JISIASR) Kolkata, India
Department of Electronics and Electrical Communication Engineering, Indian Institute of Technology, Kharagpur, India
Tissue damage due to disease or injury has been a major concern for the entire global population, and its remediation poses serious challenges to the healthcare providers, biomedical researchers, and professionals across the globe. The concern becomes manifold since some organs and tissues have very limited self‐renewal or regenerative capacity. Thus for restoring such injured or degraded tissues, we need to regenerate functional living tissue or even the whole organ artificially. This has resulted in an extremely important and emerging field of tissue engineering and regenerative medicine, which offers the potential to provide solutions for bio‐fabrication of functional tissues.
Bioprinting, the process of creating complex, living tissues using 3D printing technology has received paramount importance in recent times. The interdisciplinary technology, lying at the intersection of engineering and biology, is the backbone of regenerative medicine and tissue engineering and points to the future of modern medicine.
Using this technology, it is important to precisely position multiple cell types layer by layer using computer‐aided additive manufacturing techniques. Bioprinting is essentially a computer‐aided transfer process for assembling biologically relevant materials including biomolecules, cells, tissues, and biodegradable biomaterials, resulting in the formation of an engineered bio‐functional construct. Indeed it is a revolutionary concept in the regeneration or repair of damaged tissues by automating the layer‐by‐layer hierarchical fabrication of cell‐laden structures both in vitro and in vivo.
Some of the early models of 3D bioprinting technology used computer‐controlled ink‐jet printer or graphics plotter and were used for precisely positioning the cells on a 2D substrate. This work provided the fundamental platform for 3D bioprinting. From those early efforts in mid‐1980s, the interdisciplinary endeavor in 3D bioprinting and regenerative medicine technology has progressed substantially over the past three and a half decades, making personalized medicine a reality.
Since the original native tissues of a patient have their own distinct complex architecture as well as 3D organization and distribution of cells and extracellular matrix, it remains a significant challenge to precisely understand the complexity of native tissues from a structural and functional perspective. It holds endless promise for revolutionizing healthcare and various industries. From regenerative medicine to pharmaceutical testing and beyond, the possibilities offered by bioprinting are vast and continually expanding. However, the growth in this field also holds the numbers of existing challenges that need to be addressed by the scientific community.
In this context, the book 3D Bioprinting from Lab to Industry, edited by Prosenjit Saha, Sabu Thomas, Jinku Kim, and Manojit Ghosh, has opened up the exciting world of bioprinting and its modern industrial applications.
The book, written by some of the esteemed scientists in this field, will embark on a voyage through the intricate landscapes of bioprinting. The contributors of each chapter have shared their experiences to present the fundamental challenges along with the solutions that lie in each area. From the first chapter, where the authors explain the fundamental principles of 3D bioprinting, the readers will enjoy a journey through the diverse facets of bioprinting – controlling this translational technology to the design, fabrication, and applications of biomaterials and bioinks at industrial scale, the book covers all the important aspects of 3D bioprinting.
The broad overlap of additive manufacturing with tissue engineering has transcended the boundaries of conventional medicine, presenting enormous potential for a future where organs can be printed on demand at laboratory, customized to individual needs with precision. It holds endless promise for revolutionizing healthcare for various industries. From regenerative medicine to pharmaceutical testing and beyond, the possibilities offered by bioprinting are vast and continually expanding. However, the growth in this field also holds the numbers of existing challenges that need to be addressed by the scientific community.
Because of its affordability, commercial viability, and capability to fabricate complex and hollow constructs, the extrusion‐based bioprinting, one of the most common techniques in bioprinting field, has been employed to print living cells, tissue constructs, organ modules, and even organ on‐a‐chip devices. In this book, the extrusion‐based 3D bioprinting has been covered in adequate details for the readers. Bioinks are formulation of materials suitable for processing by an automated biofabrication technology. With the advancement of technology – especially the introduction of extrusion‐based printing techniques that use a small‐diameter nozzle to deposit bioinks for the fabrication of complex constructs – individual cells and cell aggregates lack the ability to withstand the shear stress.
Starting with an introduction of the fundamental principles of bioink, the authors have presented here the translational technology for the design, fabrication, and applications of biomaterials and bioinks at industrial scale.
Furthermore, the book presents the industrial applications of bioprinting, showcasing how this technology can be used in personalized medicine, from planning to implementation, through case studies and laboratory‐based research outcomes. The profound impact of AI and machine learning on the design of 3D bioprinting has also been included here. The processing parameters on the design of scaffolds, organoids, and cell/tissue models during printing process have also been discussed in detail by the authors.
With a lucid introduction to the realm of bio printing, followed by cellular requirements and preparation for bio printing, the authors have discussed various materials used for bioprinting. Bioprinting in regenerated organs, 4D bioprinted multiresponsive structure, the controlling factors in bioprinting, in situ bioprinting, machine learning, and in particular deep learning techniques in 3D bioprinting, nanomaterial and design of scaffolds, organoids, and cell/tissue models during printing process have been discussed in detail by the authors.
How to plan a bioprinting project and how it moves from laboratory to industry are two very important issues, which have been discussed here. The industrial applications of bioprinting, showcasing how this technology is utilized in personalized medicine from planning to implementation, have been discussed here through case studies and lab‐based research outcomes. Finally, toxicity issues hold paramount importance in 3D bioprinting, and along with this comes the most pertinent ethical issues involved in this area. These have also been adequately discussed in this book.
For researchers, industry professionals, students, or anyone curious about the present and the future of 3D bioprinting and tissue engineering, this book will provide valuable insights into this rapidly evolving field. I hope that the book inspires and informs readers about the remarkable possibilities presented by 3D printing in shaping the future of modern medicine and healthcare industry.
Happy reading!
1Introduction of 3D Printing and Different Bioprinting Methods
Asmita Biswas1, Baisakhee Saha1, Hema Bora1, Pravin Vasudeo Vaidya1,2, Krishna Dixit1, and Santanu Dhara1
1 School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India
2 Advanced Technology Development Centre, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India
1.1 Introduction of 3D Printing: Principles and Utility
3D printing (3DP), also known as additive manufacturing (AM), solid‐freeform (SFF), and rapid prototyping (RP), is a fabrication technique using model data, where 3D structures are fabricated using controlled layer‐by‐layer deposition [1]. It was first described by Charles Hull in 1986, followed by production and commercialization by S. Scott Crump and his company Stratasys [2]. The basic subcategories of 3DP are stereolithography, fused deposition modeling, selective laser melting, electronic beam melting, and laminated object manufacturing [3]. 3DP involves scaffold construction by material addition, with high geometric precision reducing material waste. The primary procedure comprises data acquisition and synthesis of meshed 3D computer models in computer‐aided design (CAD), followed by surface tessellation language (STL) file creation. This is followed by the slicing of mesh data into multiple 2D layer files and transferring them to a 3DP machine for fabrication [4]. Manufacture of complex designs, low cost, ease of access, and rapid and environment‐friendly procedures are some of the advantages of 3DP in industrial, research, healthcare, and biomedical sectors.
1.2 Ink Preparation and Printability
The choice of the base material as well as the recipe of its preparation to cater to the need for 3DP are of utmost importance. Bioink is the material used to produce either engineered or artificial living tissue using 3DP. It is the cell‐trapping milieu composed of a multicomponent aqueous mixture that usually forms gels. This sol‐gel transition of bioink is offered either by ionic bonds, covalent bonds, hydrogen bonds, or van der Waals interactions. Bioinks may be hydrogels, decellularized extracellular matrix, cell pellets, or tissue spheroids, of which hydrogels are the most common [5] due to their cell adhesion, growth, and proliferation capability since they absorb and retain large amounts of water. Ink for 3D bioprinting can be subdivided into two categories: cell‐laden inks called bioink and cell‐free inks called biomaterial ink. The bioinks usually consist of hydrogel precursors and are directly printed into Petri dishes filled with media and antibodies, whereas the biomaterial inks are usually utilized to print 3D scaffolds wherein the cells can be seeded on the scaffold under controlled conditions [6].
An ideal bioink should provide mechanical stability, stiffness, viscosity, surface tension, structural integrity, and biological ability – biocompatibility and biodegradability [7]. Many natural polymers like alginate, agarose, gelatin, chitosan, collagen, fibrin, and hyaluronic acid and synthetic polymers like polylactic acid (PLA), poly‐D,L‐Lactic acid (PDLLA), polylactic‐co‐glycolic acid (PLGA), polyvinyl alcohol (PVA), acrylonitrile butadiene styrene (ABS), polyethylene glycol (PEG), polyether ketone (PEEK), polycaprolactone (PCL), polybutylene terephthalate, and polyurethane (PU) [8] are used as bioinks for 3DP in the form of single or multicomponent.
Printability
: The term “printability” is the ability of a bioink to form a 3D structure with accurate fidelity and integrity as per the design and the geometry. However, the terminology modulates itself according to the printing approach. For extrusion printing, the bioink must be able to form continuous filament; for the inkjet technique, it should form well‐defined droplets while for laser printing, a prominent jet is required. The different printability indices
[5]
are the following:
Extrudability
: The minimum extrusion pressure essential for printing at the desired flow rate.
Strand printability
: Comparison of the diameter of printed strands with the CAD‐generated parameters.
Integrity factor
: Comparison of the thickness of printed scaffolds with designed geometries.
Pore printability
: Comparison of the printed pores with designed internal geometry.
Irregularity
: Comparison of outer geometry of scaffolds with designed parameters in
X
,
Y
, and
Z
directions.
Rheological properties and gelation kinetics determine the printability of a bioink, which is again dictated by the type of bioprinting. Low‐viscosity bioinks are preferred in inkjet bioprinting; rapidly crosslinkable, shear‐thinning bioinks are desirable for extrusion bioprinting and photo‐crosslinkable bioinks are favorable for stereolithographic printing [9]. Rheological properties like viscosity, viscoelasticity, yield stress, shear thinning, elastic recovery, and viscoelastic shear moduli affect the printability of bioinks. The rheological properties of the crosslinked bioink must facilitate scaffold remodeling to mimic the ECM environment. This process provides physicochemical cues to the cells, promoting their spreading and proper distribution. For instance, substrates that mimic the mechanical properties and Young’s modulus (~12 kPa) of native skeletal muscles offer better myogenic differentiation [10]. The key rheological parameters for a “good” bioink are described below:
Viscosity:
Viscosity is the ratio of shear stress to shear rate and is governed by the molecular weight and concentration of the polymer. High‐viscosity inks are preferable for high‐fidelity printing but may limit cell growth within the substrate due to higher shear stress. This shear stress can be overcome by either using hydrogel inks having shear‐thinning properties or using pre‐gel solutions with lower viscosities. For e.g., alginate‐based bioinks are directly extruded into calcium solution leading to ionic crosslinking. Due to higher surface tension, viscous bioinks prevent droplet formation without any merger of the columns with one another. Hence, crosslinking agents come into the picture with the caution of appropriate concentration so as to avoid phase separation and phase change
[11]
. Temperature‐dependent hydrogen bonding or hydrophobic interactions may be exploited, as in case of gelatin, Pluronic, etc. Colloidal‐like suspensions of densely packed microgels or jammed gels also prevent exposure of cells to high shear stress
[12]
.
Viscoelasticity and yield stress:
Viscoelasticity is the property of retaining elastic shape while allowing viscous flow. It is guided by three parameters – storage modulus (G′), viscous modulus (G″), and yield stress. Tan (
δ
), the ratio between G′ and G″, gives information about the rheological characteristics of the bioink. Yield stress is the stress limit beyond which deformation occurs. The parameters of G′ and yield stress are governed by the number of crosslinks within the bioink. These crosslinks offer resistance to shape change within the yield stress. Paradoxically, though yield stress of the bioink renders shape and stiffness to the substrate, it can also deter cell encapsulation and further growth. Hence, additives like carrageenan, gellan gum, and hyaluronan are added to the bioinks to improve yield stress [
13
,
14
]. However, in stereolithography and light‐assisted bioprinting, low‐viscosity bioink is required for easy flow and for each layer to be crosslinked with each other.
Shear thinning:
Shear thinning is the phenomenon where increase in shear rate results in the decrease in viscosity. Partially crosslinked hydrogels, colloidal suspensions, polymer melts, or polymer solutions above certain critical concentrations show shear‐thinning properties with shape preservation. Shear thinning leads to decrease in viscosity in the extrusion phase, but rise in viscosity after extrusion results in shape preservation. For e.g., shape retention in printed calcium phosphate cement is due to high zero‐shear viscosity
[15]
. PCL and PLA melts, used in polymer‐based fused deposition modeling, possess intrinsic shear thinning properties due to shear‐induced disentangling and alignment of long polymeric chains
[16]
. High resting viscoelasticity of pastes, solid suspensions, and colloidal dispersion bioinks arises due to the restoration of interaction between the suspended particles, which had been disrupted due to the shear‐thinning process
[17]
. Hydrogels demonstrate non‐Newtonian fluid behavior with shear‐thinning features. So, the random polymer chains align themselves in one direction under shear force and become suitable for extrusion process.
Surface tension:
Due to surface tension, there is an attraction between the liquid molecules, which ensures a contact angle between each printed strand. When the substrate has a higher surface energy than the surface tension of the bioink, the ink spreads; conversely, lower surface energy results in less spread
[18]
. For e.g., shape fidelity in printed constructs of ceramic slurries is reduced by both surface tension and gravity. It has been observed that a reduction in surface energy leads to droplet formation instead of a cuboidal structure
[19]
.
Elastic recovery: This property explains how the bioink recovers its original solid‐like property without any distortion after undergoing deformation or transition from liquid to solid state [20]. Due to this feature, multi‐layered structures can be built up. Elastic recovery is the combination of both viscous flow and elastic recovery where the viscous modulus, G″, explains the fluid‐like behavior of bioinks, and elastic modulus, G′, defines the solid‐like behavior of bioinks imparting elastic shape recovery. While the former allows mixing of cells and extrusion, the latter allows suspension of cells. Often, these moduli vary under different conditions of temperature, stress, and shear rate.
The recovery of solid‐like behavior after extrusion through a needle must be fast to ensure good shape fidelity. The rheological evaluation of a bioink is done on the basis of the kinetics of yield stress and elastic recovery. The first step is to evaluate the effect of increasing shear stress and filament‐forming capability, followed by the measurement of viscosity as a function of shear rate to evaluate the shear thinning property. Then, recovery tests are done to investigate whether the materials can restore their elastic properties on exposure to alternating low and high sheer stress [17].
1.3 Methods of Bioprinting in Fabrication and Tissue Engineering
The essential types of bioprinting are laser‐assisted bioprinting, droplet printing, extrusion printing, and stereolithography. Laser‐assisted bioprinting comprises laser‐based ejection of material onto the substrate. Droplet printing consists of droplet ejection by different mechanisms leading to deposition on substrate and scaffold fabrication. Low‐viscosity ink and cell‐laden media‐based scaffold fabrication are primary candidates for droplet printing based on enzymatic, chemical, or mechanical‐based gelation.
Extrusion bioprinting consists of material extrusion and layer‐by‐layer deposition on substrate‐synthesizing scaffold. By far, it is the most conventional production technique in bioprinting. Stereolithography involves UV or light‐assisted photopolymerization‐based ink gelation leading to scaffold fabrication.
1.3.1 Laser‐Based Printing
Laser‐based printing utilizes a digital printing mechanism where a pulse laser is used to create a driving force for depositing biomaterial on substrate. It consists of three parts, that is, laser, ribbon, and collector (Figure 1.1). Laser used for printing has the excitation near UV range of 300–400 nm, or at UV range of 193–248 nm (Table 1.1) [26, 27]. Ribbon comprises of transparent glass, gold, or titanium as an absorbing material, and bioink consists of cells, polymer mixture, and growth factors. Laser beam pulses at a specific time period cause vaporization of the metal over the bioink, further creating pressure to form a bubble‐containing hydrogel, resulting in deposition on substrate. Laser‐assisted printing offers resolution ranges from picometer to micrometer in size controlled by viscosity of bioink, thickness of bioink coated over the ribbon, collecting substrate wettability, and air gap between the ribbon and substrate [27].
Figure 1.1 Schematic representation of types of 3D bioprinting [21] – extrusion printing, inkjet printing, selective laser printing, and stereolithography.
Source: Adam et al. [21] / Springer Nature.
Table 1.1 Comparison between the different methodologies of 3DP – laser‐based, inkjet‐based, extrusion‐based, and stereolithography [22, 23].
Source: 22,23 / Placone Jk et al. / John Wiley & Sons.
Parameters
Laser‐based
Inkjet‐based
Extrusion‐based
Stereolithography
Resolution
~20–100 μm
~30 μm
~100 μm
~5–100 μm
Speed
Slow
Fast
Medium
Fast
Surface finish
Very good
Excellent
Fair
Good
Cell viability
—
Yes
Yes
Yes
Materials
Biomaterials
Hydrogels, live cell printing
Ceramics, polymers, metals, hydrogels
Photocurable polymers
Gelation methods
Ionic thermal photopolymerization enzymatic
Ionic pH mediated thermal enzymatic
[24]
Photopolymerization, ionic pH mediated thermal enzymatic
[25]
Photopolymerization
1.3.1.1 Types of Laser Printing
Laser Direct Writing
Light direct writing (LDW) was reportedly first utilized to manufacture microlens arrays by Gale et al. in 1983. 2D and 3D scaffolds are fabricated by laser beam directed on substrate in a desired pattern. Direct writing prototyping is mediated by target translation, laser translation, or target rotation. Translation and rotation on X, Y, and Z axes result in almost six degrees of freedom [29]. The basic components of LDW consist of an optical system, a mechanical system, and a guidance system [30]. The different types of LDW include selective laser sintering/melting, micro laser sintering, and laser machining (Figure 1.2). Selective laser sintering utilizes continuous wave (Ar2+, CO2) and long pulse laser with 50 μm resolution using ceramics, polymers, and metals in tissue engineering and prosthetics applications [31]. LDW is utilized to print biological scaffolds and cell‐laden ink in customizable 2D and 3D complex geometry with high spatial resolution. Also, it aids deposition on various substrates including hydrogels, microfluidic devices, nanofibers, and living tissue. LGDW is the first laser‐based printing technique to print live cells. Interaction between light and cells occurs due to comparable refractive index of cells and media, higher the differences, stronger the interactions. Weak laser beam focused on media‐containing cells generates a gradient force resulting in hauling of cells towards laser and deposition on substrate [32]. By this technique, limited cells are deposited on substrate (2.5 cells/min). Another limitation of LDW is that cells can be transferred for limited distance (300 μm) [33]. To overcome this situation, optical fiber is used, which will transmit light as well as transfer the cells to fiber core.
Matrix‐assisted Pulsed Laser Evaporation Direct Write (MAPLE DW)
MAPLE was first developed by the US Naval Research Laboratory [34]. In MAPLE, biomaterials are blended with volatile solvents like alcohol and are frozen at −196 °C, followed by laser exposure [35]. Photon energy is converted to thermal energy and absorbed by the biomaterial present in volatile solvent. These vaporized molecules get desorbed over the desired pattern surface, whereas volatile components (possessing limited adhesion coefficient) evaporate during deposition. MAPLE DW can print a wide variety of biomaterials ranging from lower to higher molecular weights with minimum damage from condensed to vaporized state [36]. MAPLE transfers particles without disrupting their chemical and biological functionality. However, MAPLE‐based technique cannot be used for transferring live cells as they cannot be entrapped in the volatile solvent due to toxicity [37].
Figure 1.2 (a) Basic schematic of laser‐assisted printing (b) laser‐guided direct writing– laser force optically guided the cells and deposited over the substrate (c) matrix‐assisted pulsed laser evaporation: – laser melted frozen ink converting photon energy to thermal energy depositing over the substrate, (d) laser‐induced forward transfer (LIFT) on laser exposure converts photon energy to thermal energy creating a bubble and releases bioink to get deposited over the substrate.
Source:[27]. Li, 2016; [28]. Ozbolat et al. 2017.
MAPLE DW is a modification of MAPLE in which a thin coating of hydrogel is created over the quartz crystal termed as printed ribbon, absorbs the majority of laser wavelength, thus reducing the chances of genetic alteration caused by UV radiation [38]. Cells encapsulated in ink and coated over the metal ribbon were printed by MAPLE DW. Laser exposure melts down the quartz crystal, thus creating a high vapor pressure and forming a plasma bubble. This bubble bursts and allows the coating material to get absorbed into the collecting substrate. Plasma bubble formation further can be tuned by the viscosity of coated material, thickness of the coating, and laser fluence.
Laser‐Induced Forward Transfer (LIFT)
LIFT comprises CAD software, laser, cartridge, and collecting substrate. The cartridge consists of three layers – transparent quartz glass, a thin gold layer, and bottom of gold layer, which is coated with bioink. With the help of spin coating, uniform layer of bioink is created; thickness of bioink plays a great role in the formation of bubble. To maintain the consistency of the process, the rheological parameter should be controlled carefully [39]. Introducing absorbent material has successfully mitigated the detrimental effect on the live cells while printing. During the printing process, all the cells due to gravity, settle at the bottom of the coating; upon laser exposure, the quartz glass absorbs most of the radiation and then interacts with the intermediate layer here, due to which thermal energy vapor pressure is created, which forms the bubble. Then, vapor bubble accumulates energy and expands to form a jet and drive the bioink to collect substrate [40]. Bioink parameters and laser energy play a crucial role in the formation of proper jet [41].
Major limitation of laser‐based printing is the cost of fabricating scaffolds. Additionally, the metal film used for adsorption layer can lead to contamination. Choi et al. described that multiple bioink printing is difficult in laser‐based printing [42]. Printing consecutive material is time‐consuming and resolution gets compromised. The material accumulates at the bottom due to gravity, leading to contamination [43].
1.3.2 Extrusion‐Based Printing
In extrusion‐based bioprinting, hydrogel, viscous solution, or cell spheroids are extruded from nozzle on a substrate, in a layer‐by‐layer technique, using a fluid dispensing system and an automated three‐axis robotic system [44]. Basic components of extrusion printer consist of a reservoir containing material, printhead extruding material, and substrate where material is deposited. A pneumatic actuator or screw device feeds material through the cartridge into the nozzle for deposition on the substrate (Figure 1.3). Actuators regulate the positioning of nozzle on X, Y, and Z dimensions, controlling ink deposition. Scaffolds with complex geometries require sacrificial support for successful and accurate fabrication. Recent developments include co‐axial printing for core shell scaffold fabrication and multimaterial extrusion bioprinting technology proficient in extruding multiple bioinks with concise and fast switching between different reservoirs to fabricate complex multiple‐material scaffolds. The substrate requires high surface roughness and wettability whereas shear thinning, low surface tension, and shape‐retentive bioink are essential [47]. Structural integrity of the constructs is relatively superior to extrusion‐based bioprinting due to the continuous deposition of cylindrical filaments making it the most appropriate type of printing for complex 3D scaffold fabrication [48].
Figure 1.3 Extrusion printing principles. (a) Basic schematic of extrusion printing – pneumatic and screw based, (b) conventional types of extrusion bioprinting – shear thinning (DIW), co‐axial extrusion, coagulation bath‐based extrusion printing, and freeform reversible embedding.
Source:[49]. Abdolmaleki H et al. 2021 / with permission of John Wiley & Sons.
Extrusion printing is cost‐effective and rapid fabrication technique and relatively straightforward mechanism compared to the other printing methods. In addition, geometrical and fabrication parameters can be altered effortlessly according to necessity depending on the required scaffold. However, extrusion printing has restricted resolution hence the minimum scaffold sizes fabricated are between 200 and 1000 μm. Also, live cell printing is relatively complicated using extrusion printing compared to inkjet printing due to extensive shear stress impacting cell viability.
1.3.3 Droplet Printing
Droplet‐based printing presents ink deposition and direct patterning of bioink aided by computer‐based non‐contact pattern reproduction techniques. The droplet‐based printing technology has the following subtypes:
Aerosol jet
Inkjet
Electrohydrodynamic jet
Depending on ink viscosity, aerosol jet printing involves aerosol generation in the nebulization step by pneumatic or ultrasonic means (Figure 1.4). The droplets are transported through a mist tube to the print head by inert gas and are encased with a sheath gas flow at the bottom of the nozzle. Aerosols are deposited on moving substrates due to the aerodynamic interaction between carrier gas and sheath gas [49].
Figure 1.4 Schematic representation of aerosol jet printer with pneumatic and ultrasonic nebulizer.
Source: Abdolmaleki et al. [49] / with permission of John Wiley & Sons.
Electrohydrodynamic jet printing utilizes an electric field to generate fluid flow from nozzle to the substrate. Ink is forced through the nozzle from ink chamber toward the tip, utilizing air backpressure to initiate printing. The voltage applied between the substrate and the nozzle causes charge accumulation due to electric field, resulting in the pendant droplet coming out of the nozzle tip. A Taylor cone forms due to meniscus deformation as a consequence of shear stress from charge accumulation (Figure 1.5). The surface tension of the ink is overcome by electrostatic forces by exceeding the electric potential of the meniscus above optimum value, leading to discharge of jet from Taylor cone´s surface to the substrate [52].
Constraints of droplet printing involve ink flow when printed on a nonplanar surface, hence both inkjet and electrohydrodynamic printing are possible only on planar surfaces. Although aerosol jet printing resolves the issue by aerosol ejection instead of droplet ejection conformal printing remains an unresolved matter in aerosol jet technique on polyhedron geometry substrate. Aerosol and inkjet printing reportedly exhibit low resolution, limiting their applications. However, the E‐jet printing technique provides a resolution of around 100 nm, providing rapid and flexible fabrication (Table 1.2).
Table 1.2 Comparison of different modes of droplet‐based printing techniques [49].
Source: Abdolmaleki et al. [49] / with permission of John Wiley & Sons.
Characteristic
Inkjet
Aerosol Jet
E‐jet
Deposition mechanism
Electrostatic
[24]
Aerodynamic
[53]
Electrohydrodynamic
Viscosity [cP]
1–20
0.7–2500
<300
Working distance [mm]
1
1–5
<1
Print speed [mm s
−1
]
Up to 2000
Up to 200
Up to 100
Minimum line width [μm]
30
10
<0.1
Geometry of substrate
planar
Planar and nonplanar
Planar
Nozzle diameter [μm]
10–50
100–300
0.3–30
Particle size of ink [nm]
<100
<700
Variable based on nozzle diameter
Figure 1.5 (a) Schematic representation of electrohydrodynamic jet printing [50], (b) EHD jetting modes with respect to electric potential. Increasing electric potential exhibits different jetting modes namely (a) dripping, (b) pulsating, (c) cone‐jet, (d) tilted jet, (e) twin jet, and (f) multi jet.
Source: Lee et al. [51] / Adapted with permission of American Chemical Society.
1.3.4 Inkjet‐Based Printing
Inkjet‐based bioprinting is a subtype of droplet‐based printing. It utilizes pneumatic, thermal, or sonic actuation to maneuver cell‐laden microdroplets from the nozzle to a substrate [54]. The prerequisites for substrate characteristics include induction of viscous forces, wettability, and high friction coefficient, while the bioink should have nonfibrous nature, low viscosity, and high rate of gelation [55]. Inkjet‐based bioprinting was one of the first mechanisms for 2D cell printing due to advantages like high cell viability and droplet size [54].
Figure 1.6 (a) Schematic representation of CIJ inkjet printing mechanism, (b) thermal actuator‐based DOD printing, (c) piezoelectric actuator‐based DOD printing.
Source: Abdolmaleki et al. [49] / with permission of John Wiley & Sons.
The mechanism of inkjet printing involves ejection of ink droplets on a substrate from nozzles of various diameters [56]. Generally, two ejection modes are exhibited in inkjet printing, namely, drop on demand (DOD) and continuous inkjet (CIJ) (Figure 1.6). DOD printing involves ink droplet ejection on demand, and ejection from nozzle is governed by trigger signals through thermal or piezoelectric actuators present in the printhead. In thermal actuators, trigger signal passes through a heat layer, forming vapor bubbles, leading to drop ejection due to liquid expansion in nozzle. Whereas in piezoelectric actuators, trigger signal leads to piezoelectric element deformation, resulting in droplet ejection from nozzles, CIJ printing involves the ejection of continuous cylindrical ink column by means of an acoustic wave, fabricated using piezoelectric ceramic, in order to obtain minimum surface energy according to Rayleigh–Plateau instability rule. An electric field applied by two parallel deflector plates maneuvers drop deflection to the appropriate position on the substrate while the stray drops are collected in the gutter followed by recirculation into printhead nozzles [57]. Manipulation of optimum cell density, low droplet resolution due to the presence of biopolymers, clogging, and limited biomaterial compatibility resulted in reduced accuracy and mechanical instability [53, 57].
1.3.5 Stereolithography 3D Printing
Stereolithography apparatus (SLA) printing is the oldest printing technique, which uses a computer‐controlled laser beam to photopolymerize liquid resin to print objects layer‐by‐layer. Charles Hull patented this method of fabrication in 1968 [59]. The fundamental elements of SLA printing include a computer‐aided design (CAD) of tissue or organs of interest, a source of illumination, and a vertically moving stage in the resin tank. SLA 3DP is based on photopolymerization, wherein the photons from UV or visible light sources dissociate the photoinitiator into a high‐energy radical state that interacts with monomers and produces polymeric chains. Biofabrication of 3D printed scaffold depends on the types and concentration of photoinitiator and the intensity of the light source [60].
SLA uses different approaches:
(i) masked base writing, and (ii) direct laser writing
[61]
. SLA uses either a laser beam or projected light to photopolymerize the ink. Masked base writing, also called digital light processing‐based SLA, uses digital micromirror technology to project an image of a predetermined pattern or a layer of a 3D CAD model by rerouting incoming light from a UV source. The schematic is shown in (
Figure 1.7
a). Direct laser writing (DLW) uses a laser beam to trace the 2D image on the surface of the resin (
Figure 1.7
b). This bottom‐up approach is widely adopted wherein the fabrication platform is set just below the tank's surface and is filled with ink
[64]
. After the photopolymerization of one layer, the platform is lowered for the printing of the second layer. DLW with multiphoton polymerization prints scaffold with high resolution. Here, resin polymerization occurs via femtosecond light pulses from near‐infrared laser and optical components to focus the laser beam. The movement of the focal plane of the laser leads to the fabrication of complex 3D structures with intricate features
[65]
. DLW is more time‐consuming and expensive than the DLP technique.
Compared to the other bioprinting techniques, SLA is a faster technique with resolutions ranging from 5–100 μm [66, 67]. It is less time‐consuming and independent of complexity or size as the entire image of the 2D slice is projected at once and gets photopolymerized upon irradiation. Owing to nozzle‐free fabrication and shear stress independence, the cells could maintain up to 85–90% viability [68, 69]. Additionally, the temperature is low, which is also favorable for cells. Despite promising results in the fabrication of 3D scaffolds, it suffers from limitations. During post‐processing, the structure undergoes shrinkage compromising the resolution [70]. The scarcity of biomaterials sensitive to photopolymerization, expensive equipment/photoinitiator, and cytotoxicity associated with uncured photoinitiator are other major drawbacks of the SLA approach.
Figure 1.7 Schematic showing SLA based on (a) digital light processing and (b) direct laser writing [62]. Schematic representation of stereolithographic 3D printing.
Source: Reproduced with permission Gross et al. [63] / American Chemical Society.
1.4 Scaffold Modeling and G Coding
1.4.1 Scanning Technology
There are many 3D scanning technologies available for medical purposes, to collect and capture geometry data. Computed tomography (CT) and magnetic resonance imaging (MRI) are more favored in medical imaging, and the scanned data resembles the slice format for layer‐by‐layer RP.
1.4.2 CT Imaging
CT is a process of generating an image by the use of computer‐assisted capturing of a series of X‐ray images, through image acquisition at different angles, to
