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MECHANICAL ENGINEERING IN BIOMEDICAL APPLICATIONS The book explores the latest research and developments related to the interdisciplinary field of biomedical and mechanical engineering offering insights and perspectives on the research, key technologies, and mechanical engineering techniques used in biomedical applications. The book is divided into several sections that cover different aspects of mechanical engineering in biomedical research. The first section focuses on the role of additive manufacturing technologies, rehabilitation in healthcare applications, and artificial recreation of human organs. The section also covers the advances, risks, and challenges of bio 3D printing. The second section presents insight into biomaterials, including their properties, applications, and fabrication techniques. The section also covers the use of powder metallurgy methodology and techniques of biopolymer and bio-ceramic coatings on prosthetic implants. The third section covers biofluid mechanics, including the mechanics of fluid flow within our body, the mechanical aspects of human synovial fluids, and the design of medical devices for fluid flow applications. The section also covers the use of computational modeling to study the blockage of carotid arteries. The final section elaborates on soft robotic manipulation for use in medical sciences. Audience The book provides practical insights and applications for mechanical engineers, biomedical engineers, medical professionals, and researchers working on the design and development of biomedical devices and implants.

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Table of Contents

Cover

Table of Contents

Series Page

Title Page

Copyright Page

Preface

Acknowledgments

Part I: ADDITIVE MANUFACTURING

1 The Role of Additive Manufacturing Technologies for Rehabilitation in Healthcare and Medical Applications

1.1 Introduction

1.2 Classification of the Additive Manufacturing Process

1.3 AM Materials for Medical Applications

1.4 Biomedical and Healthcare Applications of AM

1.5 Conclusion and Future Outlook

References

2 Artificial Recreation of Human Organs by Additive Manufacturing

2.1 Introduction

2.2 Role of Additive Manufacturing for Human Organs

2.3 Role of Artificial Recreation

2.4 Role of Additive Manufacturing in Orthopedics

2.5 Types of Bioadditive Manufacturing

2.6 Conclusion

References

3 Advances, Risks, and Challenges of 3D Bioprinting

3.1 Introduction

3.2 3D Bioprinting

3.3 Biomaterials and Bioinks

3.4 Applications of 3D Bioprinting

3.5 A Case Study

3.6 Conclusions

References

4 Laser-Induced Forward Transfer for Biosensor Application

4.1 Introduction

4.2 Biosensor

4.3 Laser-Induced Forward Transfer (LIFT)

4.4 Laser-Induced Forward Transfer for Biosensor Manufacturing

4.5 Outlook and Conclusion

References

Part II: BIOMATERIALS

5 The Effect of the Nanostructured Surface Modification on the Morphology and Biocompatibility of Ultrafine-Grained Titanium Alloy for Medical Application

5.1 Introduction

5.2 Materials and Methods

5.3 Results and Discussion

Conclusions

Acknowledgments

References

6 Powder Metallurgy-Prepared Ti-Based Biomaterials with Enhanced Biocompatibility

6.1 Introduction

6.2 Powder Metallurgy of Ti-Based Materials

6.3 Laser Surface Treatment of Materials for Enhanced Human Cell Osteodifferentiation

Conclusion

Acknowledgments

References

7 Total Hip Replacement Response to a Variation of the Radial Clearance Through

In Silico

Models

7.1 Introduction

7.2 The Musculoskeletal Multibody Model

7.3 The Lubrication/Contact Model

7.4 Simulations

7.5 Conclusions

References

8 Techniques of Biopolymer and Bioceramic Coatings on Prosthetic Implants

8.1 Introduction

8.2 Driving Factors for the Application of Coatings

8.3 The Development of Implant Coatings

8.4 Conclusions

References

9 Mechanical Behavior of Bioglass Materials for Bone Implantation

9.1 Introduction on Bio Materials

9.2 Aim and Objective of the Work

9.3 Role of REEs (CeO

2

, La

2

O

3

, and Sm

2

O

3

)

9.4 Uses of Rare Earth Elements

9.5 Biomaterials

9.6 Simulated Body Fluid

9.7 Bioactive Glasses

9.8 Bioactive Composites

9.9 Area of Biomaterials

References

10 Biomedical Applications of Composite Materials

10.1 Introduction

10.2 Different Types of Composites Used in Biomedical Applications

10.3 Application of Composites in Tissues

10.4 Application of Composites in Dentistry

10.5 Application of Composites in Total Joint Replacements

10.6 Application of Composites in Hip Joint Replacement

Conclusions

References

Part III: BIOFLUID MECHANICS

11 Materials Advancement, Biomaterials, and Biosensors

11.1 Introduction

11.2 Design of Biomaterials

11.3 Polymers

11.4 Metals as Biomaterials

11.5 Bioactive Material and Concept of Bioactivity

11.6 Biocompatibility of the Titanium Binder Element

11.7 Classification

11.8 Interaction Between Biomaterials and Biological Systems

11.9 Biomaterials: Protein Surface Interactions

11.10 Dental Material Cavity Fillers

11.11 Bridges, Crowns, and Dentures

11.12 Bone Fractures

11.13 Biosensors

11.14 Biosensor Classification

11.15 Biosensors: Precursors of Contemporary Biomaterial Succession

References

12 Blockage Study in Carotid Arteries

12.1 Introduction

12.2 Numerical Model and Its Implementation

12.3 Results and Discussion

12.4 Conclusion

References

13 Mechanical Properties of Human Synovial Fluid: An Approach for Osteoarthritis Treatment

13.1 Introduction

13.2 Osteoarthritis and Its Treatments

13.3 Viscosupplements

13.4 Synovial Mimic Fluid/PVP

13.5 Conclusion

References

14 Artificial Human Heart Biofluid Simulation as a Boon to Humankind: A Review Study

14.1 Introduction

14.2 Biofluid Simulation

14.3 Heart Valve Fluid Flow

14.4 Artificial Heart as a Boon to Humankind

14.5 Conclusion

References

Part IV: ROBOTICS

15 Robotics in Medical Science

15.1 Introduction

15.2 Minimally Invasive Surgery (MIS)

15.3 Human–Robot Interaction

15.4 Robotic Manipulation

15.5 The Role of Human–Computer Interaction (HCI)

15.6 Soft Robotics in Medicine

15.7 Haptics in Medicine

15.8 Automation and Control

15.9 Dental

15.10 CAD/CAM

15.11 Conclusion

References

16 A Research Perspective on Ankle–Foot Prosthetics Designs for Transtibial Amputees

16.1 Introduction

16.2 Biomechanics of Biological Ankle and Foot

16.3 Prosthetic Foot

16.4 Conclusion

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 3D bioprinting applications of biomaterials.

Chapter 2

Table 2.1 Types of orthopedic structures using additive manufacturing.

Table 2.2 Comparison of the additive manufacturing process for biomedical appl...

Chapter 4

Table 4.1 Summary of studies on manufacturing biosensors using LIFT through th...

Chapter 5

Table 5.1 EDS analysis of the nanostructured surface of the CG and UFG TNZ for...

Table 5.2 Roughness values of the bare and nanostructured surfaces of CG and U...

Chapter 7

Table 7.1 Values assumed by the hip radial clearance.

Chapter 8

Table 8.1 Types of coatings and their advantages.

Chapter 9

Table 9.1 Types of tissue attachment for biomaterials based on the nature of t...

Table 9.2 Clinical applications of silica-based bioactive glasses [15].

Chapter 11

Table 11.1 An overview of the development of metals, plastics, and ceramics in...

Table 11.2 List of a few ceramics and glass as bioactive materials.

Table 11.3 Few noteworthy contributors from the mid-16th century to the 21st c...

Table 11.4 Classification of biomaterials based on conventional patterns with ...

Table 11.5 Classification of biosensors based on signal transduction and biore...

Chapter 12

Table 12.1 Grid independency test for case 1, i.e., normal artery.

Table 12.2

Grid independency test for case 2, i.e., 50% blocked carotid artery...

Table 12.3 Grid independency test for case 3, i.e., 75% blocked carotid artery...

Table 12.4 Coefficients obtained from ANSYS Fluent for the Carreau model [19].

Table 12.5 Model, methods, and initialization conditions for the present work.

Chapter 13

Table 13.1 International knee OA guidelines and recommendations for intraartic...

List of Illustrations

Chapter 1

Figure 1.1 Typical process layout for the additive manufacturing process.

Figure 1.2 Applicability of AM technologies for the production of 3D organ mod...

Figure 1.3 Types of 3D bioprinting.

Figure 1.4 Jetting-based 3D bioprinting [6].

Figure 1.5 Extrusion-based 3D bioprinting [6].

Figure 1.6 Laser-assisted bioprinting [6].

Figure 1.7 Laser-based stereolithography [6].

Figure 1.8 Characteristic improvement in the AM material with various matrix a...

Figure 1.9 The use of several additive manufacturing processes and a range of ...

Figure 1.10 Applications of the additive manufacturing in biomedical and healt...

Figure 1.11 (a) Medical models; (b) implants; (c) tools, instruments, and part...

Figure 1.12 Chronology of additive manufacturing scientific and technical adva...

Figure 1.13 Utilization of AM technologies in healthcare fields.

Chapter 2

Figure 2.1 Artificial recreation organs vs. natural human organs.

Figure 2.2 Technology relation for artificial recreation of the function of th...

Figure 2.3 Details about artificial functional recreation for biomedical appli...

Figure 2.4 Types of TEBVs.

Figure 2.5 Accidental bone replacement by a 3D additive manufactured supportiv...

Figure 2.6 Classification, details, and applications of organoids.

Chapter 3

Figure 3.1 A schematic diagram of a 3D bioprinter named “MITO,” Avay Bioscienc...

Figure 3.2 A 3D-bioprinted gelatin scaffold extruded at an optimum temperature...

Figure 3.3 A solid layer of GelMA formed on UV crosslinking at a wavelength of...

Figure 3.4 A 3D-bioprinted alginate human ear scaffold printed using extrusion...

Figure 3.5 Three to four consecutive layers of biomaterials are extruded from ...

Chapter 4

Figure 4.1 General overview of the components of a biosensor [39].

Figure 4.2 Classification of biosensors based on various types of bioreceptors...

Figure 4.3 Graphical illustration of the LIFT process [110].

Figure 4.4 Classification of LIFT-related processes.

Figure 4.5 LIFT deposition characteristics at different fluence magnitudes [11...

Figure 4.6 (a) Deposited structure and (b) the relationship between

d

and

L

[1...

Chapter 5

Figure 5.1 Scheme of (a) the HPT apparatus and (b) the difference in the dimen...

Figure 5.2 The microstructure of the undeformed (a) and high-pressure torsion-...

Figure 5.3 The morphology of the nanostructured surface of CG TNZ (a–d) and UF...

Figure 5.4 Variation of the average value of (a) the diameter of the nanotubes...

Figure 5.5 The dependence of current density on the anodic oxidation time at a...

Figure 5.6 The elements of the spectra of the modified surface of (a) CG TNZ a...

Figure 5.7 AFM surface images for the (a) initial CG TNZ, (b) CG TNZ surface a...

Figure 5.8 Fractions of surviving (

K

) for (a) MRC-5 and (b) L929 cells during ...

Figure 5.9 The MRC-5 cells on the surface of the (a) initial CG TNZ, (b, c) an...

Figure 5.10 The L929 cells on the surface of the (a) initial CG TNZ, (b, c) an...

Chapter 6

Figure 6.1 Characteristic fragmented shape of HDH titanium powders—(a): Ti pow...

Figure 6.2 Characteristic spherical plasma atomized titanium powder: powder si...

Figure 6.3 The microstructure of solar pressureless sintered Ti in a solar fur...

Figure 6.4 Comparison of (a) oxygen and (b) nitrogen concentration in powders ...

Figure 6.5 Comparison of (a) modulus of elasticity and (b) yield stress for va...

Figure 6.6 Comparison of (a) tensile strength and (b) elongation to fracture f...

Figure 6.7 Comparison of PM production steps in the cold pressing method and s...

Figure 6.8 Bone tissue behavior on the PM-prepared Ti compact with (a) low sur...

Figure 6.9 SEM images of the irradiated surfaces demonstrating how laser fluen...

Figure 6.10 Characteristic HDH titanium powder and graphite particle shapes: (...

Figure 6.11 3D surface maps of the laser-modified PM Ti–graphite surface (

E

p

=...

Figure 6.12 3D surface maps of the laser-modified PM Ti–graphite surface (

E

p

=...

Chapter 7

Figure 7.1 The body’s Lagrangian coordinates.

Figure 7.2 Joints considered in the multibody model. (a) Revolute joint scheme...

Figure 7.3 The wrapping muscle scheme.

Figure 7.4 Geodesics starting from the muscle AB intersection points.

Figure 7.5 The geodesic wrapping muscle.

Figure 7.6 The Hill muscle–tendon model.

Figure 7.7 The Hill muscle-tendon surface.

Figure 7.8 Hip reference frames.

Figure 7.9 Hip tribosystem reference frame.

Figure 7.10 The Reynolds equation spherical discrete domain and cross stencil.

Figure 7.11 Coupling the multibody and the tribological models.

Figure 7.12 The lower limb system during the gait cycle.

Figure 7.13 The right knee joint Lagrange multipliers.

Figure 7.14 The right semitendinosus muscle states.

Figure 7.15 The right hip tribological input.

Figure 7.16 The hip joint tribological output fields.

Figure 7.17 The tribological outcomes during the gait cycle.

Figure 7.18 Eccentricity response to the radial clearance variation.

Figure 7.19 Pressure and separation response to the radial clearance variation...

Figure 7.20 Pressure and separation response to the radial clearance variation...

Figure 7.21 Maximum pressure, minimum separation, and contact area fraction re...

Figure 7.22 Wear volume response to the radial clearance variation.

Chapter 8

Figure 8.1 Benefits of the application of bioactive coating on implants.

Figure 8.2 Schematic diagram of the above-discussed coating processes.

Figure 8.3 Schematic representation of the biomimetic coating, microwave-assis...

Chapter 9

Figure 9.1

In vitro

and

in vivo

performance (©Pearson Education).

Figure 9.2 Classification of bioactive materials according to the United State...

Figure 9.3 A kinetic diagram illustrating the bioactivity of SiO

2

–Na

2

O–CaO bio...

Figure 9.4 Specific biological activities can be induced by exploiting differe...

Figure 9.5 Two-dimensional presentation of a random glass network is a non-per...

Chapter 10

Figure 10.1 Biomedical applications of composites.

Figure 10.2 Composites used in biomedical applications.

Chapter 11

Figure 11.1 Visualization of the biomedical applications of biomaterials: orth...

Figure 11.2 Diagram depicting the components of biosensors (reproduced from Pe...

Chapter 12

Figure 12.1 (a) Proportion of cardiovascular disease mortality in India based ...

Figure 12.2 Flow diagram for the simulation steps.

Figure 12.3 Geometry used in the design modular.

Figure 12.4 Triangular meshed carotid artery with 50% stenosis.

Figure 12.5 Viscosity behavior of blood flow using the Carreau model (data obt...

Figure 12.6 Velocity contour in the healthy, 50%, and 75% blocked carotid arte...

Figure 12.7 Velocity fluctuation with artery length in the normal carotid arte...

Figure 12.8 Velocity fluctuation with artery length in 50% stenosis carotid ar...

Figure 12.9 Velocity fluctuation with artery length in 75% stenosis carotid ar...

Figure 12.10 Wall shear stress (WSS) distribution contour in the healthy, 50%,...

Figure 12.11 Pressure distribution contour in the healthy, 50%, and 75% blocke...

Figure 12.12 Molecular viscosity contour in the healthy, 50%, and 75% blocked ...

Figure 12.13 Mass distribution contour in the healthy, 50%, and 75% blocked ca...

Chapter 13

Figure 13.1 Six types of interventions considered for the treatment of OA.

Chapter 14

Figure 14.1 Artificial heart [7].

Figure 14.2 The regulatory mechanism of an artificial heart [7].

Figure 14.3 (a) The 3D model of artificial hear. (b) The inlet air-pressurized...

Figure 14.4 (a) Boundary conditions and (b) equivalent (von Mises) stress of t...

Figure 14.5 An electrically powered prosthetic heart system [7].

Chapter 15

Figure 15.1 Schematic representation of medical microrobotics [19].

Figure 15.2 Schematic representation of state-of-the-art technology for the de...

Figure 15.3 Outline of some of the major technological milestones related to s...

Figure 15.4 Kinematics of the robotic manipulator.

Figure 15.5 Schematic representation of soft and rigid manipulators in the 2D ...

Figure 15.6 Earthworm-inspired soft robots classified based on actuation metho...

Figure 15.7 Schematic representation of visual haptics image for manipulation ...

Chapter 16

Figure 16.1 Leading causes of below-knee amputation in the Indian context.

Figure 16.2 Various planes of motion such as (a) sagittal, (b) transverse, and...

Figure 16.3 Various movements of the foot [17].

Figure 16.4 Gait cycle of the biological right foot with different phases [18]...

Figure 16.5 Various stages of the stance phase.

Figure 16.6 Broad classification of ankle prosthetics.

Figure 16.7 ESAR prosthesis. (a) Generalized framework of ESAR. (b) Customized...

Figure 16.8 ESAR prosthesis. (a) Multiple plates of ESAR. (b) Single spring pr...

Figure 16.9 CERS prosthesis [17].

Figure 16.10 Multi-array active prostheses [17].

Figure 16.11 LPP active prosthesis [17].

Figure 16.12 CAS prosthesis [17].

Guide

Cover Page

Table of Contents

Series Page

Title Page

Copyright Page

Preface

Acknowledgments

Begin Reading

Index

WILEY END USER LICENSE AGREEMENT

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Scrivener Publishing100 Cummings Center, Suite 541JBeverly, MA 01915-6106

Publishers at ScrivenerMartin Scrivener ([email protected])Phillip Carmical ([email protected])

Mechanical Engineering in Biomedical Applications

Bio-3D Printing, Biofluid Mechanics, Implant Design, Biomaterials, Computational Biomechanics, Tissue Mechanics

Edited by

Jay Prakash Srivastava, Dražan Kozak, Vinayak Ranjan, Pankaj Kumar, Ranjan Kumar

and

Shubham Tayal

This edition first published 2024 by John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA and Scrivener Publishing LLC, 100 Cummings Center, Suite 541J, Beverly, MA 01915, USA© 2024 Scrivener Publishing LLCFor more information about Scrivener publications please visit www.scrivenerpublishing.com.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions.

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For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com.

Limit of Liability/Disclaimer of WarrantyWhile the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials, or promotional statements for this work. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read.

Library of Congress Cataloging-in-Publication Data

ISBN 978-1-394-17452-2

Cover image: Pixabay.ComCover design by Russell Richardson

Preface

This book explores the latest research and developments related to the interdisciplinary field of biomedical and mechanical engineering. The book collects contributions from leading international scholars and practitioners, who offer their insights and perspectives on the research, key technologies, and mechanical engineering techniques used in biomedical applications.

The book is divided into several parts that cover different aspects of mechanical engineering in biomedical research. The first part focuses on the role of additive manufacturing technologies, rehabilitation in healthcare applications, and artificial recreation of human organs. The part also covers the advances, risks, and challenges of bio 3D printing. The second part presents insight into biomaterials, including their properties, applications, and fabrication techniques. The part also covers the use of powder metallurgy methodology and techniques of biopolymer and bio-ceramic coatings on prosthetic implants. The third part covers biofluid mechanics, including the mechanics of fluid flow within our body, the mechanical aspects of human synovial fluids, and the design of medical devices for fluid flow applications. The part also covers the use of computational modelling to study the blockage of carotid arteries. The final part elaborates on soft robotic manipulation for use in medical sciences.

We would like to thank all the contributors to this book for their invaluable insights and expertise. Their contributions have made this book a truly interdisciplinary and international exploration of mechanical engineering in biomedical applications. We would also like to acknowledge the support of the publisher and the editorial team who have worked tirelessly to bring this book to fruition. We hope that this will be a useful resource for mechanical engineering students and researchers who are interested in biomedical applications, as well as medical professionals who want to understand the principles behind the design and development of medical devices and related technologies.

Finally, we offer our gratitude to our families and loved ones for their support and encouragement throughout the editorial process.

The EditorsNovember 2023

Acknowledgments

We would like to express our gratitude to all the contributors to this book, who have generously shared their expertise and insights on the topic of “Mechanical Engineering in Biomedical Applications: Bio-3D Printing, Biofluid Mechanics, Implant Design, Biomaterials, Computational Biomechanics, Tissue Mechanics”. Their contributions have made this book a comprehensive and insightful exploration of the challenges and opportunities in the domain.

We would also like to thank the publisher and the editorial team for their support and guidance throughout the editing process. Their dedication and hard work have been instrumental in bringing this book to fruition.

We are grateful to our families and loved ones for their support and encouragement throughout the editing process. Their patience and understanding have been invaluable.

The Editors

Part IADDITIVE MANUFACTURING

1The Role of Additive Manufacturing Technologies for Rehabilitation in Healthcare and Medical Applications

Vidyapati Kumar1, Ankita Mistri2* and Abhishek Mohata3

1Department of Mechanical Engineering, Indian Institute of Technology, Kharagpur, West Bengal, India

2Department of Mechanical Engineering, Indian Institute of Technology, Dhanbad, Jharkhand, India

3Department of Mechanical Engineering, Jalpaiguri Government Engineering College, West Bengal, India

Abstract

Additive manufacturing (AM) is a rapidly evolving technology that is being utilized to produce medical components across a wide range of sectors. Since each patient is unique in terms of health and dental care, AM has enormous potential for personalized and customized therapy. In addition to its bespoke design and reduced manufacturing time and cost, it also offers a broad and extended opportunity for the biological mimicry of desired complicated states of physiological devices. Scaffolds with a fitted outer shape and a porous internal structure may be created via additive manufacturing, which is critical for repairing vast segmental bone lesions. The scaffold-building process includes scaffold design, additive manufacturing, and post-treatments. This research attempts to provide a more systematic assessment of the use of various AM processes and their need in the current era with their classifications in the healthcare and medical field utilizing different biomaterials, as well as the scope of future research for advancing the medical field using various AM processes.

Keywords: Biomaterials, additive manufacturing, implants, scaffolds, prosthetics

1.1 Introduction

In this contemporary period of the Fourth Industrial Revolution, the marketplace must constantly improve itself via continual innovation and customization, in which the innovation and deployment of unconventional manufacturing processes play a vital role. Additive manufacturing (AM) has already been shown to play a significant part in the unconventional manufacturing process. Additive manufacturing, also known as 3D printing, rapid prototyping, or free-form fabrication, is an operation in which materials are joined by layer-by-layer deposition to produce a three-dimensional product from a computer-aided design (CAD) model thereby eliminating the need for various machining processes. AM technologies, which use metal powders to create intricate and sophisticated 3D geometry, are a burgeoning industry. AM technologies have been highlighted as a critical manufacturing priority and are considered one of the essential components of Industry 4.0, having the potential to amend the global manufacturing industry. Currently, it has been noted that the demand for AM surged fast after the start of COVID-19 in many industries where the economic downturn suffered as a consequence of the efforts implemented to limit the pandemic. Additive manufacturing is already enabling a design and industrial revolution in various industries, including aviation, power, automobile, healthcare, tooling, and consumer products.

The typical manufacturing procedure for printing tissues using the AM technique has been depicted in Figure 1.1. The first phase in this process is data collection, in which the data about the organ or portion of the body that needs to be printed are obtained using medical imaging methods such as X-ray and computed tomography (CT) scan. Once the data are obtained, a 3D model of the component is created using computer-assisted design (CAD) and computer-aided manufacturing (CAM) processes. The bioinks used for 3D bioprinting are then chosen, and the bioprinting settings and resolutions are calibrated. Once the material has been 3D bioprinted, its functionality is tested in an incubator or bioreactor to confirm stability, cell viability, tissue development, and so on. Following these procedures, the printed component is now ready for in vitro testing, disease modeling, and in vivo implantation in the human body, saving a significant amount of life in healthcare systems.

Figure 1.1 Typical process layout for the additive manufacturing process.

From this perspective, it is important to grasp the importance of additive manufacturing technologies like 3D bioprinting in healthcare and biological sciences. In the healthcare and medical fields, the general practice is to do preclinical research using animal-based models, notably rodents [1]. From a regulatory standpoint, it is critical and obligatory to conduct this experiment using animal-based models in order to bring forth the most current therapeutic breakthroughs from preclinical to clinical trials. These problems have not been highlighted for many decades, but a recent surge in opprobrium based on humanitarian and scientific considerations has shown that around 80% of putative treatments perish in clinical trials while having effectiveness and safety in preclinical investigations [2]. Potential underlying causes include inadequate characterization of relevant animal models [3, 4], a lack of acceptable experimental quality in in vivo investigations, and significant interspecies-related differences to humans in areas such as anatomy, (patho)physiology, and immunology. Many disorders that develop in humans are not ubiquitous in nature in animals; thus, an artificial disease induction is necessary to simulate the diseases, and even if the animals display identical diseases, the underpinning pathophysiology condition is entirely unknown. The mouse-based animal model for SARS coronavirus infection has recently shown severe encephalitis, which is not seen in human pathogenesis. Hence, as seen in Figure 1.2[5], the translational utility of preclinical animal models has been called into doubt owing to a lack of concordance and reproducibility. Figure 1.2 displays the high expense of drug development as well as their relatively high failure rates in the clinical phase, raising concerns about the current applicability of research methodologies. To address the aforementioned limitations, additive manufacturing technologies play a critical role in which a 3D organ or human-based models may be generated in order to undertake fundamental and preclinical research. As a result, this AM technology has attracted conscientious scrutiny due to its usefulness in producing a human-based model as a replacement for animal models for scientific purposes.

Figure 1.2 Applicability of AM technologies for the production of 3D organ models [5].

1.2 Classification of the Additive Manufacturing Process

Several 3D printing technologies have been created to bioengineer three-dimensional tissue or organ frameworks for biomedical purposes, as demonstrated in Figure 1.3. The most extensively utilized forms of 3D bioprinting processes are extrusion-based bioprinting, laser-assisted bioprinting, and laser-based stereolithography. The effectiveness of each printing technique is heavily reliant on biomaterial choices and functions.

Figure 1.3 Types of 3D bioprinting.

1.2.1 Jetting-Based Bioprinting

Jetting-based bioprinting is the earliest printing method, in which bioinks are used to print. These bioinks may be either natural or manufactured substances that help in cell adherence, propagation, and replication. Bioink is pushed with force via a nozzle in this approach, resulting in a spray of droplets. These printers may have a single or several print heads. A chamber and a nozzle are both included in each print head. The surface tension of the fluid keeps the bioinks near the nozzle opening. In three ways, pressure pulses are injected into the print head chamber. As seen in Figure 1.4, it is provided via piezoelectric inkjet, thermal inkjet, or electrostatic bioprinting. The actuator in the piezoelectric inkjet generates pressure pulses to deposit the bioinks; however, certain print heads need back pressure to complement the pressure pulses to make droplets of bioinks. When a voltage pulse is supplied to a thermal inkjet printer’s thermal actuator, it locally warms the bioink solution. Figure 1.4[6] shows that local heating produces a vapor bubble. This bubble rapidly expands and shrinks, generating a force burst inside the fluid compartment and driving the bioink droplet to defy interfacial tension and accumulate on the scaffold. Thermal inkjet printers may discharge biological materials such as proteins and mammalian cells, among other things. Bioink droplets are created in electrostatic bioprinters by increasing the capacity of the fluid compartment with the aid of a bioink fluid attached to the plate. After that, the pressure plate deflects between the electrode and the plate once the voltage is applied. Finally, as the voltage drops, the bioink is evacuated as the pressure plate re-establishes its position, and printing happens.

Figure 1.4 Jetting-based 3D bioprinting [6].

1.2.2 Extrusion-Based Bioprinting

Extrusion-based bioprinting is based on the notion of applying extrusion pressure to the bioink, which is very beneficial for tissue regeneration and repair. The bioink contained in this process is largely deposited using pneumatic pressure, a mechanical pressure in the form of a screw or piston, and lastly, the substrate is extruded out, as illustrated in Figure 1.5[6]. The robotic stage controller governs and controls the whole extrusion process of the bioprinter. The head can move in three directions, namely, x, y, and z, and the bioink may be dispensed directly onto the substrate underneath it. These printers are capable of dispensing high cell density bioinks, unique hydrogels with a wide range of viscosities, and biodegradable thermoplastics like polycaprolactone. When compared with inkjet printers, extrusion bioprinting reduces the possibility of bioink clogging. The main disadvantage of extrusion is that we must guarantee that the shear force is not so great that it impairs cell viability.

Figure 1.5 Extrusion-based 3D bioprinting [6].

1.2.3 Laser-Assisted Bioprinting

Laser-assisted bioprinting is another popular method for bioprinting live cells onto a substrate. This printing is made feasible by using a high-intensity light source or light with a long wavelength. A laser pulse, focusing lens, donor slide, energy absorption layer, donor substrate, and collector slide are the main components of a laser bioprinter, as depicted in Figure 1.6. The focusing lens in Figure 1.6 concentrates the high-intensity light, after which the bioink is concentrated on the collection slide and the printed output is formed. Unlike inkjet printers, laser printers have no nozzles and may therefore deposit large densities of bioinks without clogging, as demonstrated in Figure 1.6[6].

Figure 1.6 Laser-assisted bioprinting [6].

1.2.4 Laser-Based Stereolithography

It is a free-form process for depositing light to cross-linked polymer materials, as demonstrated in Figure 1.7[6]. Most stereolithography techniques use UV light, directed onto the photocurable resin’s surface. When the resin has dried, the platform travels higher and is ready to deposit a new coat of resin. This procedure is repeated till the product is finished. Despite its benefits, stereolithography has an extended processing time.

1.3 AM Materials for Medical Applications

Biomaterials have been employed in regulated pharmaceutical delivery techniques, sutures and adhesives, cardiac bypass, rehabilitative and orthopedic devices, ocular devices including corneas and corrective lenses, and dentistry. Several experiments have been carried out in the field of biomedical engineering, such as neurosurgical bone grinding, in which multicriteria decision-making and optimization tools have been successfully employed to fine-tune the parametric setting, which aids in the 3D bioprinting process [7]. Several components, including titanium, have been utilized to generate therapeutic implants. Bioceramics, polymers, metals, and composites are just a handful of the materials accessible. Table 1.1 outlines the current biological applications for biomaterials.

Different kinds of reinforcing materials may be used to improve the qualities of 3D printed polymer composite products as depicted in Figure 1.8. Nylon was employed as the matrix material, whereas carbon, glass, and Kevlar were used as reinforcing materials to achieve a significant increase in tensile strength and fracture resistance [35]. To increase the tensile and thermal characteristics of the polymer used in biomanufacturing, acrylonitrile-butadiene-styrene (ABS) as a matrix material and carbon fiber as a reinforcing material were blended [36, 37]. In another work, ABS was combined with graphene to increase the thermal characteristics of polymeric biomaterials [38]. In the instance of Epoxy resin [39], fiberglass was utilized as a reinforcing material to increase tensile strength and fatigue life. When epoxy acrylate [40] is combined with titanium dioxide, it has been discovered that the polymer improves in terms of tensile and flexural strength and hardness. To achieve an increase in tensile strength and fatigue life, a nylon mix with fiberglass as a reinforcing material is used. Figure 1.8 depicts a list of all matrix materials, reinforcing materials, and their accompanying characteristic enhancements. As a result, it can be shown that polymeric biomaterials, when appropriately combined with matrix and reinforcing material, greatly increase material characteristics, which is highly important during the bioprinting process of various components as needed.

Figure 1.7 Laser-based stereolithography [6].

Table 1.1 3D bioprinting applications of biomaterials.

References

Biomaterial

Applications

[8]

Silicones, hydrogels

Advances in ophthalmology such as intraocular lenses (IOL), contact lenses

[

9

11

]

Polymeric component, metallic material, ceramic material, PU, PE, PBE, PP, SS

Vascular prosthesis, mechanical gates, stent, cardiovascular pumping systems, blood bags, and catheters are all examples of products that may be used in the field of cardiology.

[

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PCL, silk, collagen

Nerve regeneration scaffolds are used in both the central and peripheral nervous systems.

[

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PLLA, PDLA

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PLGA

Pharmaceutical delivery

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Note: polyurethane (PU), polyesters (PE), polybutesters (PBE), polypropylene (PP), stainless steel (SS), polycaprolactone (PCL), poly(l-lactic acid) (PLLA), poly(lactic acid), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), Poly(l-lactic acid) (PLLA), poly(d-lactic acid) (PDLA), poly-para-dioxanone (PPD), low-density polyethylene (LDPE), high-density polyethylene (HDPE), poly(methyl methacrylate) (PMMA), polydimethylsiloxane (PDMS), polyamides (PA), carbon nanotubes (CNT), and composites.

Figure 1.8 Characteristic improvement in the AM material with various matrix and reinforcement materials.

Bioinks are fluid compositions that comprise three or four matrix constituents and are supplied into a bioprinter before being accumulated on the scaffold. Such scaffolds allow cells to connect, survive, bioaccumulate, and replicate after printing [41]. This cell proliferation phenomenon is important in tissue regeneration because it assists in the rehabilitation of dead body tissues. These multicomponent bioinks are utilized to produce various tissue constructions. The reason for employing multicomponent bioinks is because natural polymers such as gelatin and collagen are extensively utilized bioinks that aid in cell adhesion and migration. However, they have limited mechanical capabilities; to compensate for these limitations, various additives and biomaterials are combined to make a multicomponent biomaterial with enhanced qualities. Rheological characteristics of multicomponent bioinks are critical; they must be accurately managed in order to provide optimum printability and structural stability of the structure. Multiple bioinks may be combined in multicomponent bioinks to provide varied stiffness. These bioinks, which are constructed of cross-linked polymers, may solidify immediately after bioprinting. If they harden too soon, they may jam the printer nozzle. If it solidifies too slowly, the structure will collapse. These bioink multimaterial combinations should not be hazardous in the short or long term [42]. Bioinks are further subdivided into shear thinning and shear thickening materials [43]. Shear thinning materials allow printers to avoid using shear force, and they restore their shape after shear force is removed. Gelation occurs in shear thickening materials in response to chemical and physical stimuli. When exposed to UV radiation, chemical cross-linking occurs. The same biomaterial bioink cannot be used to print all tissues and organs because it may not meet the mechanical and functional needs of tissues or organs such as multiplication and dissemination. Some biomaterials, such as polyethylene glycol (PEG), have variable molecular weight and may join printed tissue, but they do not proliferate. Gelatin and fibrin, for example, are examples of natural biomaterials with poor mechanical characteristics. As a result, hybrid bioinks are created by combining more than one bioink, which is responsible for improving component quality as well as providing an environment conducive to cell growth, and these hybrid bioinks have acquired widespread acceptance. Figure 1.9 depicts some of the molecular varieties of bioinks that may be mixed to form a hybrid bioink that can be used in various additive manufacturing processes.

Figure 1.9 The use of several additive manufacturing processes and a range of molecular bioink types.

1.4 Biomedical and Healthcare Applications of AM

As illustrated in Figure 1.10, additive manufacturing technologies are widely used in the medical and healthcare fields such as the fabrication of medical devices and surgical tools, drug delivery and pharmaceutical industries, orthopedics and prosthesis devices, virtual surgical planning and operation planning, dentistry, and tissue engineering applications. Medical equipment and surgical tools include glass frames and lenses, hearing aids, 3D printed medical instruments other than hearing aids such as stents, and so on [41, 44]. 3D printed drug-releasing implants, 3D printed ingestible tablets, and transdermal distribution are all examples of drug delivery. Organoids and 3D models, 3D printing implants, and bone regeneration are case studies of the tissue engineering applications of AM technology.

Figure 1.10 Applications of the additive manufacturing in biomedical and healthcare sectors.

Figure 1.11 (a) Medical models; (b) implants; (c) tools, instruments, and parts for medical devices; (d) medical aids, supportive guides, splints, and prostheses; and (e) biomanufacturing [45].

Figure 1.11 depicts several examples of AM technology uses in each of the categories [45]. Figure 1.11(a) depicts preoperative skull and heart models. The craniomaxillofacial implants are depicted in Figure 1.11(b), and the dental drilling guide, reduction, forceps, and nose and throat swabs are depicted in Figure 1.11(c). Figure 1.11(d) shows a tailored and mobile external support, whereas Figure 1.11(e) shows a framework for zygomatic bone replacement and resorbable orbital implants.

1.5 Conclusion and Future Outlook

Based on the aforementioned descriptive study, it can be stated that additive manufacturing technologies proved to be extremely successful and efficient in making body tissues, organs, 3D models, and scaffolds using 3D bioprinting procedures. These approaches offer enormous potential for developing implants such as porous scaffolds, cellular structures, and body organs, and by using these methods, diverse tissues and body organs may be repaired, which is highly important in medical areas. Bioinks are employed in this technique to create this complex structural framework for cell growth and proliferation. Figure 1.12 depicts the evolution of several components using AM methods over a three-decade period. Some of the advances made in these three decades of study include rapid prototyping, rapid casting, rapid tooling, automotives, medical jigs and guides, implants, nanomanufacturing, and in situ biomanufacturing.

Figure 1.12 Chronology of additive manufacturing scientific and technical advancements, illustrating previous, current, and futuristic possibilities.

Figure 1.13 Utilization of AM technologies in healthcare fields.

Figure 1.13 shows that AM technologies have the potential to produce around 21% of dental equipment, including implants and surgical guides for dental applications; 17% of artificial body parts; 15% of lab and testing equipment; 15% of surgical instruments; 13% of medical devices; 12% of knee joints; and the remaining 7% of human body parts [46].

Future potential includes full-body organ development and manufacture utilizing AM technology. Furthermore, various environmental elements such as pressure, heat, air moisture, and radiation may be combined by employing 4D bioprinting technologies, so that the product generated using AM technologies is synergic to the biological human body. Miniaturization and sterilization of bioprinters and accompanying equipment, as well as making these systems user-friendly for end-user clinicians, will be secondary design priorities in the future.

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Note

*

Corresponding author

:

[email protected]

2Artificial Recreation of Human Organs by Additive Manufacturing

Neetesh Soni* and Paola Leo

Engineering Innovation Department, University of Salento, Via per Arnesano, Lecce, Italy

Abstract

Additive manufacturing is a technology that allows the creation of complex, customized parts and devices through the layering of materials. In the medical field, additive manufacturing is used in a variety of applications, including the creation of prosthetic limbs, surgical guides, and implantable devices. Prosthetic limbs and other assistive devices can be created using additive manufacturing techniques to ensure a perfect fit for the patient and to reduce costs. Customized surgical guides can also be created to assist in complex surgeries, such as cranial or spinal procedures, by providing a precise template for the surgeon to follow. Additive manufacturing can also create implantable devices, such as dental implants and spinal cages. Those devices can be tailor-made for the individual patient, decreasing the complication rate of surgery. In addition, researchers are exploring using 3D printing technology to create bioprinted tissue and organ models for medical research and drug testing.

Additive manufacturing is, therefore, a promising technology that has the potential to revolutionize the medical field. So, in this chapter, the authors will analyze the current applications of additive manufacturing in the biomedical field and the future perspective.

Keywords: Artificial recreation, bioimplantation, additive manufacturing, artificial intelligence programming, cellular tissue mechanics

2.1 Introduction

The additive manufacturing (AM) process, also known as 3D printing, is a technology that can create artificial human organs. This is done using a 3D printer to build up layers of materials, such as cells, to create a functional organ. Creating an artificial organ using 3D printing is known as bioprinting. The technology is still in the early stages of development and has not yet been used to create functional human organs for transplantation [1–3]. However, researchers have been able to use 3D printing to create small parts of organs, such as blood vessels and heart tissue. Artificial recreation of human organs (ARHO) combines cells, materials, and biochemical factors to create functional structures that mimic natural organs [4–7]. This field aims to develop replacement organs for damaged or diseased and to create new organs for people who are born without them or suffer from organ failure. This is done by growing cells in a lab and then using them to build the organ’s structure. ARHO by AM is a relatively new technology that has the potential to revolutionize the field of medicine, along with other materials, such as hydrogels or collagen, to create functional human organs. The first step in bioprinting is to create a digital model of the organ to be printed. This can be done using imaging techniques such as computed tomography scan and magnetic resonance imaging (CT scans or MRIs). Once the digital model is created, the 3D printer can use this information to build the organ layer by layer [8–10]. One of the significant challenges in bioprinting is ensuring that the cells stay alive and continue to function correctly once they have been printed. Investigators have found that using hydrogels or collagen as a support material can help to keep the cells alive and healthy during the printing process. Another challenge is printing the complex architecture of human organs [11]. Researchers have been able to print small parts of organs, such as blood vessels and heart tissue, but printing a fully functional organ is still a work in progress and still in the early stages of development [12–15].

Despite these challenges, bioprinting can potentially change how we think about organ transplants. If investigators can develop a way to bioprint functional human organs, it could end the shortage of organs for transplantation. Additionally, bioprinting could be used to create personalized organs for patients with specific genetic conditions, and researchers are also exploring the potential for bioprinting to help in drug discovery and testing.

2.2 Role of Additive Manufacturing for Human Organs

In AM, the role of 3D printing has the potential to revolutionize the field of organ transplantation by creating functional, anatomically correct replacement organs using a patient’s cell. Investigators are currently exploring bioprinting for various organs, including the heart, liver, and kidneys [16–18]. However, the technology needs much more development and research, and many challenges need to be overcome before it can be used to create functional replacement organs for human patients. These challenges include developing methods for printing large, complex organs with multiple types of cells and keeping the cells alive and functional during the printing process. Despite these challenges, the potential benefits of bioprinting, including reduced wait times for organ transplants and the elimination of the need for immunosuppressive drugs, make it a promising area of research.

Several factors affect the success of using 3D printing for human organs, including the availability of suitable materials, the ability to create complex structures and vasculature of the organ, and the ability to coax cells to grow and differentiate into the appropriate tissue types. The essential human organs that generally require transplant or replacement are represented in Figure 2.1 as natural organs of the human body. Its applications extend beyond these examples, as a variety of damaged organs can also be replaced. Such as artificial functional skin, lungs, kidney, pancreas, intestines, corneas, bone marrow, ears, limbs, and heart tissue recovering these also can be replaced by AM with the help of the Medical industries.

Figure 2.1 Artificial recreation organs vs. natural human organs.

2.3 Role of Artificial Recreation

Artificial recreation of human cells and organs refers to using technology to create simulations or digital models of the structure and function of human cells and organs. It can include things like 3D models, computer simulations, and bioprinting. The classification of artificial recreation of human cells and organs can be based on the type of technology used, such as 3D printing [18], tissue engineering [19], and organ-on-a-chip [20]. The types of artificial recreation of human cells and organs are represented in Figure 2.2 below.

Medical science, additive manufacturing, and other relative backgrounds have created several applications for the artificial functional recreation of cells and organs for the human body, such as medical research, replacement of damaged organs, medical training, and drug development, as shown in Figure 2.3 below.

Tissue-engineered blood vessels (TEBVs) are artificial blood vessels created in a laboratory using biological materials such as cells, biomaterials, and growth factors. They are used to replace or repair damaged or diseased blood vessels in the human body [21, 22]. There are several types of TEBVs, shown below in Figure 2.4.

Figure 2.2 Technology relation for artificial recreation of the function of the human body.

Figure 2.3 Details about artificial functional recreation for biomedical applications.

Figure 2.4 Types of TEBVs.

Autologous TEBVs: These blood vessels are created using the patient’s own cells, such as endothelial cells or smooth muscle cells. They are less likely to be rejected by the patient’s immune system but may require multiple surgeries to harvest the necessary cells

[23]

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