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3D Printing Technology in Nanomedicine
3D Printing Technology in Nanomedicine
3D Printing Technology in Nanomedicine
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3D Printing Technology in Nanomedicine

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3D Printing Technology in Nanomedicine provides an integrated and introductory look into the rapidly evolving field of nanobiotechnology. It demystifies the processes of commercialization and discusses legal and regulatory considerations. With a focus on nanoscale processes and biomedical applications, users will find this to be a comprehensive resource on how 3D printing can be utilized in a range of areas, including the diagnosis and treatment of a variety of human diseases.

  • Examines the emerging market of 3D-printed biomaterials and their clinical applications, with a particular focus on both commercial and premarket tools
  • Examines the promising market of 3D-printed nanoparticles, nanomaterial, biomaterials, composite nanomaterial and their clinical applications in the cardiovascular and chemotherapy realms
  • Develops the concept of integrating different technologies along the hierarchical structure of biological systems
LanguageEnglish
Release dateMar 30, 2019
ISBN9780128158913
3D Printing Technology in Nanomedicine

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    3D Printing Technology in Nanomedicine - Nabeel Ahmad

    3D Printing Technology in Nanomedicine

    Nabeel Ahmad, PHD

    Assistant Professor & Head, School of Biotechnology, IFTM University, Moradabad, India

    P. Gopinath, PHD

    Associate Professor, Department of Biotechnology, Joint faculty in Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Rajiv Dutta, PHD, FAAST, FASR

    Professor and Dean, Faculty of Applied Sciences and QNS Chair Professor, Center for Interdisciplinary Life Sciences, Dr. KN Modi University, Newai-Banasthali, India

    Table of Contents

    Cover image

    Title page

    Copyright

    List of Contributors

    Preface

    Chapter 1. 3D Printing in Medicine: Current Challenges and Potential Applications

    Introduction to Three-Dimensional Printing

    Process of 3D Printing

    Historical Perspective

    Types of 3D Printing Technologies

    Applications of 3D Printing in Medicine

    Challenges and Barriers to 3D Printing

    Summary

    Chapter 2. Techniques and Software Used in 3D Printing for Nanomedicine Applications

    Introduction

    Software Used for 3D Printing of Nanomaterials for Biomedical Applications

    Current Status of 3D Printing Techniques and Software for Biomedical Applications

    Challenges and Future Prospects

    Conclusion

    Chapter 3. Fabrication of Biopolymer-Based Organs and Tissues Using 3D Bioprinting

    Overview of 3D Bioprinting

    Biopolymers as Bioinks

    Prominent 3D Bioprinting Techniques Used in Biopolymer-Based Fabrication of Scaffolds

    Various Biopolymers Employed for Scaffold Fabrication

    Biopolymer-Based Nanocomposites for 3D Printing

    Advantages and Disadvantages

    Concluding Remarks

    Acknowledgments

    Chapter 4. Polymeric Materials for 3D Bioprinting

    Introduction

    Types of Synthetic Polymers

    Factors Affecting Bioprinted Constructs

    Application of Synthetic Polymers in 3D Bioprinting

    Limitation and Future Perspective

    Conclusion

    Acknowledgments

    Chapter 5. 3D Print Technology for Cell Culturing

    Introduction

    3D Printing in Cell Culture

    Applications of 3D Bioprinting in Cell Culture

    3D Bioprinting and Stem Cell Culture

    4D Bioprinting

    Summary

    Chapter 6. 3D Bioprinting for Organs, Skin, and Engineered Tissues

    Introduction

    Tissue Engineering Methods

    Bioink

    Organ Printing: Skin Tissue Engineering

    Angiogenesis in Tissue-Engineered Grafts

    3D Bioprinting in Neuroregenerative Medicines: A Future Perspective

    Summary

    Chapter 7. 3D Printing for In vitro and In vivo Disease Models

    Introduction

    3D Printing

    3D Printing for Disease Models

    3D Printed Disease Models

    Conclusion and Future Scope

    Chapter 8. 4D and 5D Printing: Healthcare’s New Edge

    Introduction

    4D and 5D Bioprinting Technology

    4D Printing Method

    5D Printing

    4D and 5D Printing in Medical Research

    Biomaterials for 4D and 5D Bioprinting in Medicine

    Applications and Examples of 4D Printing in Healthcare

    Challenges in 4D and 5D Printing

    Summary and Future Outlook

    Chapter 9. Market Demands in 3D Printing Pharmaceuticals Products

    Overview

    Challenges in 3D Printing of Pharmaceutical Products—Regulatory Considerations

    3D Printing of Oral Pharmaceutical Products: Polypills

    3D Printing of Topical Pharmaceutical Products: Patches and Microneedles

    3D Printing of Sustained-Release Implants: Hydrogels

    Future Perspectives and Concluding Remarks

    Index

    Copyright

    3D Printing Technology in Nanomedicine   ISBN: 978-0-12-815890-6

    Copyright © 2019 Elsevier, Inc. All rights reserved.

    No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

    This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

    Notices

    Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verifi cation of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

    Publisher: Matthew Deans

    Acquisition Editor: Simon Holt

    Editorial Project Manager: John Leonard

    Production Project Manager: Sreejith Viswanathan

    Cover Designer: Matthew Limbert

    Typeset by TNQ Technologies

    3251 Riverport Lane

    St. Louis, Missouri 63043

    List of Contributors

    Jyoti Ahlawat,     Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, TX, United States

    Nabeel Ahmad, PhD,     Assistant Professor & Head, School of Biotechnology, IFTM University, Moradabad, India

    Ashish, M.Tech,     Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    M. Paloma Ballesteros

    Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Instituto Universitario de Farmacia Industrial, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Shweta Bharti,     Biomedical Informatics Centre, ICMR-National Institute of Traditional Medicine, Department of Health Research, Belagavi, India

    Jose R. Cerda,     Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Raquel Fernandez-Garcia,     Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Apoorva Goel,     Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Manashjit Gogoi, PhD,     Assistant Professor, Biomedical Engineering, North Eastern Hill University, Shillong, India

    P. Gopinath, PhD,     Associate Professor, Department of Biotechnology, Joint faculty in Centre for Nanotechnology, Indian Institute of Technology Roorkee

    Roorkee, India

    Khushboo Gulati, PhD,     Research Associate, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Swati Haldar,     Department of Metallurgical & Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, India

    Harsha Hegde,     Biomedical Informatics Centre, ICMR-National Institute of Traditional Medicine, Department of Health Research, Belagavi, India

    Alok Kumar, PhD,     Research Associate, Department of Chemistry and Biochemistry, University of Texas at El Paso, TX, United States

    Manish Kumar,     Department of Electrical Engineering, College of Engineering, Bharti Vidyapeeth, Pune, India

    Pramod Kumar, M.Tech,     Scientist, Biomedical Informatics Centre, ICMR-National Institute of Traditional Medicine, Belagavi, India

    Debrupa Lahiri,     Department of Metallurgical & Materials Engineering, Indian Institute of Technology Roorkee, Roorkee, India

    Aikaterini Lalatsa,     Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom

    Ishita Matai, PhD,     Ubiquitous Analytical Techniques Division, CSIR-Central Scientific Instruments Organisation, Chandigarh, India

    Mukesh Kumar Meher,     Research Scholar, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Priya Mukherjee, MSc,     Department of Environmental Science and Engineering, Indian Institute of Technology (ISM), Dhanbad, India

    Mahesh Narayan, PhD,     Professor, Department of Chemistry and Biochemistry, University of Texas at El Paso, El Paso, TX, United States

    L. Fernando Pérez-Ballesteros, PhD,     Universidad Europea de Madrid, Villaviciosa de Odón, Madrid, Spain

    Krishna Mohan Poluri, PhD,     Associate Professor, Department of Biotechnology, Joint faculty in Centre for Nanotechnology, Indian Institute of Technology Roorkee

    Roorkee, India

    Rocky Raj, M.Tech,     Ubiquitous Analytical Techniques Division, CSIR-Central Scientific Instruments Organisation, Chandigarh, India

    Ankita Rani, M.Tech,     Department of Environmental Science and Engineering, Indian Institute of Technology (ISM), Dhanbad, India

    Partha Roy, PhD,     Professor, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Subarna Roy,     Biomedical Informatics Centre, ICMR-National Institute of Traditional Medicine, Department of Health Research, Belagavi, India

    Abhay Sachdev, PhD,     Ubiquitous Analytical Techniques Division, CSIR-Central Scientific Instruments Organisation, Chandigarh, India

    Nitin Sahai, M.Tech,     Assistant Professor, Biomedical Engineering, North Eastern Hill University, Shillong, India

    Pichiah Saravanan, PhD,     Associate Professor, Environmental Nanotechnology Laboratory, Department of Environmental Science and Engineering, Indian Institute of Technology (ISM), Dhanbad, Dhanbad, India

    Dolores R. Serrano, PhD

    Assistant Professor, Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Instituto Universitario de Farmacia Industrial, School of Pharmacy, Universidad Complutense de Madrid, Madrid, Spain

    Alexandr Vinogradov, PhD,     Director, BioChem Cluster, International Laboratory Solution Chemistry of Advanced Material and Technologies, ITMO University, Russia

    Preface

    Research in nanotechnology has surely promoted drug manufacturing and has extreme advantages in the medicinal field with revolutionary effects. The older generations of drug had extreme limitations, but on the other hand, nano drugs possess good therapeutic value. Nano-based drugs and imaging agents have been developed as novel agents to prevent, detect, and cure diseases. The recent applications of additive manufacturing are more exciting and have generated rapid developments in nanomedicine. However, there is a paucity of knowledgeable books in this field. This book describes the medicinal discovery and tissue replacement strategies by 3D printing.

    This book consists of nine chapters. Chapter 1 gives a brief introduction to 3D printing in medicine, with current challenges and potential applications. It describes its history and how it has revolutionized healthcare. This chapter also explains the applications and further outlook of the field. Chapter 2 deals with the techniques and software used in 3D printing. Chapter 3 is related to the fabrication of biopolymer-based organs and tissues. 3D bioprinting technology promises to bridge the gap between artificially engineered tissue constructs and native tissues. The chapter briefs about the application of this technology in the fabrication of biomimetic constructs of several representative tissues and organs, including blood vessels, heart, liver, and cartilage. It is a huge achievement in this field, as it has led to potential solutions for further development. Chapter 4 explains the sources of polymeric materials for 3D bioprinting. This chapter discusses the currently used polymeric materials and those under research and development for use in medicine and tissue repair and regeneration. Chapter 5 broadly organizes 3D cell culture and its analysis, which are more physiologically relevant than biochemical assays. The relevant information about the microenvironment and the cell to cell interactions, including their biological process in vivo, are also explained. Chapter 6 widely explains the process of 3D bioprinting for organ, skin, and engineered tissues. This chapter deals with the generation and transplantation of several tissues, bone, and cartilaginous structures. 3D printing of in vitro and in vivo disease models is discussed in Chapter 7. The vital goal for writing this chapter was to discuss in detail the mechanisms of human disease by additive manufacturing. In this chapter the studies about the diseased tissues in vivo and in vitro explain us about the cellular and molecular factors independently.

    Chapter 8 deals with the advancements in the 4D and 5D healthcare technologies. This chapter divulges the latest developments of additive manufacturing, i.e., 4D and 5D bioprinting. The most important factor discussed in this chapter is about the difference between the material used in 3D printing and in 4D and 5D printing. Chapter 9 is the concluding chapter and it deals with the market demands in the 3D printing of pharmaceutical products in a safe and effective way. These drugs have porous structures and are quite smaller in size and are helpful for patients who often have swallowing difficulties, such as patients with tumors and Alzheimer disease.

    Chapter 1

    3D Printing in Medicine

    Current Challenges and Potential Applications

    Ashish, M.TECH, Nabeel Ahmad, PhD, P. Gopinath, PhD, and Alexandr Vinogradov, PHD

    Abstract

    Since its introduction in the 1980s, the three-dimensional (3D) printing technology has evolved to revolutionize both scientific community and academician. The wide range of currently available manufacturing technologies provides a versatile platform for converting a prototype into a physical model. Importance of 3D printing is not only restricted to industrial area but the impact of 3D printing is also expanding in medical field in a wide range of applications including fabrication of patient-specific complex medical and anatomical structures, customized medical prostheses, implants and surgical tools, tissue and organ printing, 3D printed in vitro tissue models, drug screening purposes, advancement of physicians, and patient education. Despite significant and exciting improvements, there are many substantial challenges and barriers to the progression of 3D printing. In this chapter, we encompass the process of 3D printing, historical perspective, types of 3D printing technologies, their applications in medicine, and finally discuss various challenges to the progression of 3D printing in medicine. In the upcoming years, we believe that integration of researchers from different fields will address the challenges and barriers of 3D printing to transform the field of medicine.

    Keywords

    3D printing; Additive manufacturing; Organ printing; Tissue models

    Introduction to Three-Dimensional Printing

    The three-dimensional (3D) printing is a rapidly evolving revolutionary technology that is getting substantial interest from both scientific community and academician with users from various domains such as automotive, product designer, aerospace, engineers, consumer goods industry, architecture, military, chemical industry, food industry, fashion industry, and medical field.¹,² Importance of 3D printing is not only restricted to industrial area but the impact of 3D printing is also expanding in medical field in a wide range of applications including tissue designs, tissue engineering, organ printing, diagnostic platforms, dentistry, biomedical devices, anatomical models, drug designing, and delivery systems.³,⁴ It allows the fabrication of complex medical and anatomical structures specific for patients utilizing the data set from various imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) scan.⁵,⁶ In addition, it is being used in replacing, repairing the defective organs (skin, heart, and kidney), or creating new organ that will have the same functioning as that of original human organs.⁷ Anything ranging from jewelry, eyeglasses to clothing and medical implant, prosthetic devices, and car parts to the therapeutic drug can be printed in almost any shape or geometry using this technology. Essentially, it converts an idea or concept into a prototype by extracting design from 3D computer-aided design (CAD) files, thereby allowing the fabrication of user-defined products and physical objects with precise digital control.⁸ It is a methodology where materials such as powder, metal, alloy, thermoplastics, polymeric, ceramic, wood, paper multimaterial, and biological materials (living cells) are positioned successively into layers on top of each other (bottom-up approach) thus enabling the fabrication of desired 3D object in a controlled manner.⁹ Therefore, 3D printing is also known by other terminologies as layered manufacturing, additive manufacturing, computer automated manufacturing, rapid prototyping, or solid freeform technology (SFF).⁸ In conventional or subtractive methodologies (molding, machining, forming, casting, injection, laser cutting), final object or design is being formed by successively subtracting the material from the bulk substance. Usually, nonstandard geometries and multimaterial object are not possible with these processes due to the inability of the tool used.¹⁰,¹¹ In contrast, 3D printing is a technique where objects are constructed additively by placing specific material in layers one cross-sectional layer at a time.¹⁰ Therefore, when compared with conventional or subtractive manufacturing processes, 3D printing technologies are cost-effective, automated, rapid, easy to use, on-demand, flexible, customized, and sophisticated and thus used by the user from different backgrounds.¹²–¹⁴

    Process of 3D Printing

    First by using the digital design software (Autocad, Autodesk, Creo parametric, Onshape, Mimics, 3Matic, Solidworks, and Google SketchUp), 3D digital scanners, or phone-based applications, digital virtual 3D design of an object is created.²,¹⁵,¹⁶ Then, this digital model is converted into standard tessellation language or stereolithography (.STL) digital file format. Almost all 3D printing technologies are compatible with this file format. The .STL file includes a list of triangulated facets that indicate the information about the surfaces of the 3D model. Increased number of triangles indicates more number of data points in a text file (higher resolution of the device).² The procedure of conversion of 3D model to .STL digital file is essentially automatic in most 3D printing systems; however, sometimes there is a chance of errors during this process. Software such as Magics (Materialise) is usually used to rectify the errors in .STL files conversion. It is important to note that in general .STL file format does not include features such as type and properties of the material, color, surface texture, units, or any other feature details. Therefore, other types of file format such as additive manufacturing file format (AMF) and 3D manufacturing format (3  MF) have been introduced to conquer the drawbacks of the simple .STL format.¹⁷

    Specialized slicer software present in the 3D printer converts the .STL file into G file by slicing the design into a series of the 2D horizontal cross-section (generally in the range of 25–100  μm), and then the base of the 3D object is created by moving the print head in the x-y direction. Subsequently, the complete three-dimensional (3D) objects are created by repetitively moving the print head in the z-direction and depositing the desired material into layers sequentially.²,⁸ However, the procedure for construction of layers primarily depends on the type of 3D printing technology used. The generalized steps in the fabrication process of 3D printing are described in Fig. 1.1.

    Historical Perspective

    In early 1980s Charles Hull was working on the development of plastic devices utilizing photopolymers but the limitations of existing technology (lengthy procedures, less accuracy) motivated him to improve the technology of prototype development. In 1984 Hull invented apparatus for a new layer-by-layer printing technology named as stereolithography. Later in 1986 Hull also founded the company 3D systems and provided the term .STL that was compatible with the existing CAD software to design the 3D object. In 1987, SLA-1 3D printer was introduced. In 1988 the company came up with the first commercially available 3D printer (SLA-250).² In 1989 Deckard a graduate student at the University of Texas introduced another important technology selective laser sintering (SLS).¹⁹ In 1992 Scott Crump patented another modified 3D printing technology, that is, fused deposition modeling (FDM).²⁰ In 1993 E. Sachs and M. Cima at Massachusetts Institute of Technology (MIT) developed inkjet printing based 3D printer for printing complex shapes of polymer, metal, ceramic, plastic, etc.²,²¹ Over the years, different other companies (Z Corp., Envision Tec, Solidscape, DTM Corporation, and Objet Geometries) used 3D printers for a variety of commercialized applications. The use of 3D printing in medicine was started in the late 1990s by allowing the printing of various dental implants.² Fig. 1.2A shows the major events and developments in the evolution of both 3D printing and 3D printing in medicine. In 1999 Atala et al. at Wake Forest Institute for Regenerative Medicine fabricated the first laboratory-grown organ, that is, synthetic 3D urinary bladder scaffold that was further modified with patient’s own cells and then transplanted to the patient.²² This revolutionary procedure directed enormous progress and development in the field of medicine using 3D printing technologies. Furthermore, in 2002 the same group developed a functioning kidney by directly printing with the cell-seeded bioink instead of simply printing a bare scaffold and then coating with cells.²³ In 2003 Wilson et al. developed inkjet technology-based bioprinting hardware for protein and cell printing.²⁴ In 2004, Jakab et al. proposed that multicellular spheroids can be used as bioink for 3D organ printing.²⁵ Barron et al. also utilized laser-based technology to deposit mammalian cells onto a biopolymer matrix.²⁶ Next major breakthrough in industry happened in 2009 when Invetech and Organovo developed the first commercial bioprinter (NovoGen MMX). In 2010 Binder et al. created the skin printer that in situ bioprinted the skin onto the mice for improved healing of burns.²⁷ These breakthroughs provided a dramatic increment in the number of publications during the period of 2009–11, signified by the increased publication rate (Fig. 1.2B). In 2013 Mannoor et al. at Princeton University implemented the 3D printing technology to generate a bionic ear.²⁸ Similarly, Duan et al. at Cornell University developed artificial heart valve by 3D printing with alginate/gelatin hydrogel.²⁹ Next, in 2014 Organovo utilized the 3D printing technology to fabricate the first commercial multicellular liver tissues constructs.³⁰ In 2015 Food and drug administration (FDA) approved the first inkjet 3D printed epilepsy drug (Spritam), which was released in the market by Aprecia Pharmaceuticals.³¹ The same year Organovo announced the release of the fully 3D bioprinted kidney. In 2016 Atala’s group at Wake Forest Institute for Regenerative Medicine provided the integrated tissue–organ printer (ITOP) that allows the 3D printing of tissue constructs of any size and shape.³² Since the last 35  years, a number of 3D printing procedures and their applications in the medical field has evolved and diversified considerably.³³ According to the data obtained by ISI web of science in May 2016, the rate R, that is, the number of research articles publication about 3D printing to the number of research articles publication about 3D printing in medicine, has increased from 11.35% to the 14.93% in last 10 years (2006–15) (Fig. 1.2B).

    Fig. 1.1  Generalized 3D printing process. ¹⁸

    Fig. 1.2   (A) Major events and developments in the evolution of both 3D printing and 3D printing in medicine. (B) ISI web of science data obtained in May 2016 indicating the number of articles published in 3D printing and 3D printing in biomedicine in last 10   years (R: Rate of research articles published about 3D printing to research articles published about 3D printing in medicine). 

    Reprinted with permission from reference Zhao H, Yang F, Fu J, et al. Printing@ clinic: from medical models to organ implants. ACS Biomater Sci Eng. 2017;3:3083–3097. Copyright © 2017 American chemical society.

    Types of 3D Printing Technologies

    There are varieties of 3D printing technologies ranging from well-established methods, which have been employed in industrial settings for years, to more recent techniques under development in research laboratories that are used for more specific applications. American Society for Testing and Materials (ASTM) Committee F42 on Additive Manufacturing Technologies have grouped these technologies into seven main categories according to the methods of adding material and working principle to produce the desired 3D object (Table 1.1).³⁴ Each technology has its own pros and cons according to the desired application. The choice of 3D printing technology for a particular application is highly important and generally governed by the material parameters (type, compatibility, and availability), desired feature size, resolution, throughput, speed, and the manner how the layer to be bonded together in final object.¹¹,¹⁶,³⁵ In medical field, to deposit and pattern the biological material extrusion, thermal inkjet and laser-assisted techniques are found to be the most commonly used 3D printing technologies.³⁵ However, the other two technologies, sheet lamination and directed energy deposition, have limited medical applications.

    Vat Photopolymerization

    Photopolymerization, that is, light-induced polymerization, is a form of 3D printing where materials (photopolymers, radiation-curable resins, and liquid) collected in a vat are successively cured into layers one layer at a time by irradiating with a light source thereby providing a 2D patterned layer. This involves techniques such as stereolithography (SLA), digital light processing (DLP), and continuous direct light processing (CDLP). Among these, SLA was the first 3D printing technology invented in 1986 by Chuck Hull. In1994 SLA was first utilized in medicine as a surgical tool for alloplastic implant surgery.⁴,⁴⁰ Furthermore, depending on the orientation of light source and the surface where polymerization of the photoactive resin occurs, SLA can be broadly differentiated into two different configurations: (1) bath configuration (free surface approach) and (2) bat configuration (constrained surface approach)² (Fig. 1.3A and B). In bath configuration, polymerization of the topmost layer of the photoactive resin occurs by moving the light source line by line until the complete layer is being cured. Following the curing of the first layer, the substrate or stage is translated downwards to polymerize the subsequent layers in a bottom-up manner thereby printing the complete 3D structure. In this configuration, the thickness of the cured layer (CD) depends on various factors such as intensity of light source, scanning speed, depth of focus, and period of exposure and can be described by the following equation:

    (1.1)

    where DP is the depth of light penetration, EC is the critical energy of resin, and E is the energy of the light source (Fig. 1.3C). The parameters of UV curable liquid resin (viscosity, chemical composition, and leveling of resin), printing procedure (orientation and printing speed), and duration of postcuring also affect the printing performance.⁴¹ It has been reported that optimization of layer thickness is very important to enhance the curing efficiency. The vertical resolution depends on the thickness of cured layer while the lateral resolution is directly proportional to the diameter of UV beam (80–200  μm). Generally, the selection of UV source varies according to the resin used, but commonly used sources are Xenon lamp and HeCd laser.²,⁴² Furthermore, two-photon polymerization is also being utilized in SLA for obtaining the better resolution of the final printed 3D object. Height restriction due to vat size, laborious and lengthy cleaning procedure, resin waste, and inhibition of photo-polymerization due to chemical reaction with atmospheric oxygen are some drawbacks of bath configuration.²,⁴¹ The printing performance of bath configuration depends on various factors such as light source parameters (power, speed, and depth of focus), resin parameters (viscosity, leveling of resin, and chemical composition), and printing procedure (speed, orientation, and layer thickness).

    Table 1.1

    On the other hand, in bat configuration, a mask in the form of a digital mirror device having an array of million mirrors is being used, which enables the curing of the complete layer in a single step. In addition, different from the bath configuration in this configuration, the light source is positioned beneath the liquid resin reservoir. This light source is projected to photopolymerize the thin layer of liquid resin that is placed in between movable substrate (stage) suspended above the resin vat and the optically transparent bottom surface of the vat. Next, the stage is raised upwards to allow the uncured resin to fill the space and to detach the cured layer from the bottom surface of vat as it prints.²,³,⁴³ The bat configuration approach provides several advantages over the free surface approach and is therefore increasingly being utilized in the photopolymerization for various applications. The height of the printed object is not restricted and also it requires only small amount of liquid resin for printing. Moreover, in this configuration, curing layer is not exposed to atmospheric oxygen as the reaction happens at the bottom of the reservoir; therefore, photopolymerization inhibition is limited.⁴¹ However, the structural fidelity is found to be better in bath configuration over the bat configuration, as the mechanical separation step of the constrained surface approach may increase the roughness between the cured layers, breaking or bending of objects and may introduce stress fracture.⁴³ The printing performance of bat configuration also depends on various factors such as (1) light source (duration of exposure and intensity), (2) printing platform (resin chamber, projection system), (3) digital light processing (beam conditioning module, digital micromirror device), and (4) postcuring duration.

    In both configurations, a postcuring step utilizing the UV oven is performed to ensure the polymerization of unreactive groups, to reinforce the bonding and to improve the stability and mechanical properties of the final 3D model.²,³ Continuous direct light processing (CDLP) or continuous liquid interface production (CLIP) is the recently modified version of DLP where the optically transparent bottom layer is made oxygen permeable that provides a dead zone where no polymerization of liquid resin takes place. This prevents the adhering of the recently cured layer to the bottom surface of resin reservoir thereby enhancing the printing speed and resolution of final 3D object.⁴³,⁴⁴ In SLA, during the printing process, multiple resins cannot be processed at a time. Generally, the resins used are either acrylic or epoxy based; most of these materials are costly and brittle in nature and have a tendency of shrinking during polymerization.⁴⁵,⁴⁶ Fig. 1.3D shows the stepwise procedure for the fabrication of 3D object using stereolithography.

    Fig. 1.3   (A) and (B) Stereolithography (SLA) configurations: (A) bath configuration (free surface approach) and (B) bat configuration (constrained surface approach). (C) Parameters of UV curable resin and (D) stepwise procedure for the fabrication of 3D object using

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