Biofabrication for Orthopedics E-Book
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- Herausgeber: Wiley-VCH GmbH
- Kategorie: Fachliteratur
- Sprache: Englisch
This book not only thoroughly reveals research advances of biofabrication in orthopedics up to now but also provide perspectives for future research trends. It attracts attention of researchers from biomedicine, materials science, chemistry, pharmacy and so on.
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Veröffentlichungsjahr: 2022
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Table of Contents
Cover
Title Page
Copyright
Volume 1
Foreword from Prof. Changsheng Liu
Foreword from Prof. Yingze Zhang
Foreword from Prof. Lianfu Deng
Foreword from Prof. Cato T. Laurencin
Preface
Areas Covered in the Special Topic
Part I: Biofabrication Techniques
1 Current Progress and Technological Challenges in Translational 3D Bioprinting
1.1 Introduction
1.2 Challenges in the 3D Bioprinting Process
1.3 Conclusion and Future Perspectives
Acknowledgments
References
2 Bioceramics for Promoting Bone Regeneration
2.1 Introduction
2.2 Types of Bioceramics
2.3 Mechanical Properties
2.4 Biological Properties
2.5 Summary
Acknowledgments
References
3 3D Printing and Bioprinting Strategies Applied Toward Orthopedics
3.1 Introduction
3.2 Biomaterial Inks
3.3 3D Printing and Bioprinting Techniques
3.4 Current Challenges and Future Directions
Acknowledgments
References
4 Stem Cells and Their Application in Orthopedics
4.1 Introduction
4.2 Mesenchymal Stem Cells (MSCs)
4.3 MSC‐Derived Extracellular Vesicles (MSC‐EVs) and Exosomes
4.4 Clinical Application of Stem Cells in Orthopedics
4.5 Considerations of Stem Cells and Derivations for Clinical Usage
4.6 Conclusion
Acknowledgments
Abbreviations
References
5 Electrospinning Techniques
5.1 Introduction
5.2 Different Types of Electrospinning Techniques
5.3 Typical Applications of Electrospun Fibers in Orthopedics
5.4 Conclusion and Future Outlook
References
6 Joint Lubrication and Wear
6.1 Introduction
6.2 Natural Joint Structure
6.3 Joint Lubrication Mechanism
6.4 Joint Lubrication Behavior
6.5 Artificial Biolubricants
6.6 Artificial Joint Prosthesis
Acknowledgments
References
Note
7 Microfluidic Biotechnology for “Bone‐on‐a‐Chip”
7.1 Introduction
7.2 Basic Principles and Properties of Microfluidics
7.3 Microfluidic “Organ‐on‐a‐Chip” Technology
7.4 Conclusion and Future Perspectives
Acknowledgments
References
8 Bioactive Glasses in Orthopedics
8.1 First Bioactive Glass
8.2 Bioactive Glass Versatility
8.3 Alternative Bioactive Glasses
8.4 Bioactive Glasses in Composites and Hybrid Materials
8.5 Conclusion
Acknowledgments
References
Note
Volume 2
Part II: Biomedical Applications in Orthopedics
9 3D Printing for Orthopedics
9.1 Overview of 3D Printing Technology
9.2 Bone Tissue Engineering and 3D Printing
9.3 Cartilage Tissue Engineering and 3D Printing
9.4 Structural Requirements of 3D Printing
9.5 Biomaterials for 3D Printing
9.6 Application of 3D Printing in Cell Printing and Orthopedic Tissue Engineering
9.7 Future Prospects
Acknowledgments
References
10 Bone Implants (Bone Regeneration and Bone Cancer Treatments)
10.1 Bone Regeneration
10.2 Bone Cancer Treatments
Acknowledgments
References
Note
11 Bionic Fixation: Design, Biomechanics, and Clinical Application
11.1 Bionics and Medical Bionics
11.2 Structural Bionics in the Field of Orthopedics and Traumatology
11.3 Bionic Materials
11.4 Future Perspectives and Current Limitations
Acknowledgments
References
12 Cartilage Injury and Repair
12.1 Introduction
12.2 Pathology of Cartilage Injury
12.3 Clinical Characteristics of Cartilage Injury
12.4 Evaluation of Cartilage Injuries
12.5 Clinical Strategies of Cartilage Repair
12.6 Potential and Advanced Strategies of Cartilage Repair
12.7 Conclusion
References
13 Biofabrication for Cartilage Regeneration
13.1 Introduction
13.2 Biological Responses of Cartilage Injury
13.3 Biofabrication: Traditional Cellular Products
13.4 Biofabrication: Bioprinting
13.5 Biofabrication: Electrospinning
13.6 Biofabrication: Microfluidic
Acknowledgments
References
14 Intervertebral Disc Repair
14.1 Introduction
14.2 Technique for Intervertebral Disc Therapy
14.3 Gene Therapy for IVD
14.4 Molecular Therapy for IVD Degeneration
14.5 Biomaterial Therapy
14.6 Summary
References
15 New Prospects in Skin Tissue Engineering and Fabrication
15.1 Skin Anatomy and Related Cell Types
15.2 Types of Skin Wounds and Wound Healing Process
15.3 Treatments for Wound Healing
15.4 Skin Regeneration Using Tissue Engineering
15.5 Skin Substitutes
Acknowledgments
References
Note
16 Techniques for Biofabrication of Vascular and Vascularized Tissue
16.1 Introduction
16.2 3D Printing
16.3 Microfabrication
16.4 Electrospinning
16.5 Decellularized Vascular Tissue
16.6 Cell‐Only Fabrication
16.7 Conclusion and Outlook
Acknowledgments
References
17 Vascularization
17.1 Introduction
17.2 Is Porous Structure Needed for Vascularization?
17.3 Promotion of Vascularization in Biomaterials
17.4 Vascularization in Porous Biomaterials
17.5 Vascularization of Porous Biomaterials in Bones
17.6 Conclusion
References
18 Muscle Repair
18.1 Introduction
18.2 Anatomy of Skeletal Muscle
18.3 Pathophysiology After Skeletal Muscle Injury
18.4 Biofabrication for Skeletal Muscle Regeneration
18.5 Application and Prospect
References
19 Rotator Cuff Repair
19.1 Introduction
19.2 Histology of the Rotator Cuff Tendon‐to‐Bone Enthesis
19.3 Risk Factors Associated with High Failure Rates of Rotator Cuff Repair
19.4 Biofabrication for Rotator Cuff Repair
19.5 Biological Augmentation for Rotator Cuff Repair
19.6 Future Perspectives of Biofabrication for Rotator Cuff Repair
Acknowledgments
References
20 Tendon Repair
20.1 Introduction
20.2 Tendon Biology
20.3 Tendon Injury
20.4 Tendon Healing
20.5 Tendon Repair
20.6 Conclusion
References
21 Nerve Regeneration
21.1 Peripheral Nerve Regeneration
21.2 Spinal Cord Regeneration
21.3 Clinical Application of Nerve Conduit
21.4 Conclusion
Acknowledgments
References
Notes
Index
End User License Agreement
List of Tables
Chapter 2
Table 2.1 Ionic substitution of bioceramics.
Chapter 3
Table 3.1 Summary of 3D printing and bioprinting techniques utilized in ort...
Chapter 4
Table 4.1 Cell culture medium formulation, proliferation, and differentiati...
Table 4.2 Summary of the markers expressed by human MSCs
in vitro
.
Table 4.3 Stem cell‐based therapy for OA and cartilage defect.
Table 4.4 Clinical results for the subchondral bone MSC therapy for OA pati...
Table 4.5 International association of neurorestoratology spinal cord injur...
Table 4.6 ASIA score.
Chapter 8
Table 8.1 Summary of the most representative natural polymers used as build...
Table 8.2 Nominal glass composition (weight%).
Table 8.3 Comparison of composite and hybrid materials developed for bone t...
Chapter 9
Table 9.1 Characteristics of different 3D printing technologies.
Chapter 10
Table 10.1 Factors that have been reported in the process of repairing bone...
Table 10.2 Effects of pore size of different materials on bone regeneration...
Table 10.3 Enneking's criteria for surgical margins in musculoskeletal tumo...
Chapter 12
Table 12.1 Overview of pre‐clinical methods for cartilage repair.
Chapter 13
Table 13.1 Evolution of autologous chondrocyte implantation (ACI).
Table 13.2 Scaffolds used in autologous chondrocyte implantation (ACI).
Table 13.3 Commercial products for cartilage or osteochondral regeneration....
Table 13.4 Working mechanisms, advantages, and disadvantages of different k...
Table 13.5 Bioinks and the related 3D printers in cartilage tissue engineer...
Table 13.6 Electrospun synthetic polymers used in cartilage engineering (wi...
Table 13.7 Microfluidic fabrication used in cartilage tissue engineering.
Chapter 14
Table 14.1 Commonly encountered changes on a degenerated IVD.
Table 14.2 Sources of cell‐based therapy for IVD repair.
Table 14.3 Commonly used carriers' vectors for gene therapy.
Table 14.4 The ongoing clinical trials of biomaterial therapy for IVD degen...
Chapter 18
Table 18.1 Advantages and shortcomings of different types of polymers.
Table 18.2 Examples of substances and functions for biofabrication.
Table 18.3 Acellular ECM scaffold could improve the functional outcomes of ...
Table 18.4 Four types of cells seeded in scaffolds and its functions.
Table 18.5 Characterization of tissue‐engineered muscle grafts and fabricat...
Table 18.6 Examples of tissue engineering approaches for the treatment of v...
Chapter 19
Table 19.1 Cellular and ECM composition of the rotator cuff tendon‐to‐bone ...
Chapter 21
Table 21.1 Summarize table of representative bio‐fabricated products for pe...
Table 21.2 Summarize table of representative bio‐fabricated products for sp...
Table 21.3 Simplified Seddon and Sunderland classification.
List of Illustrations
Chapter 1
Figure 1.1 Steps in bioprinting process. (1) Imaging of the damaged tissue; ...
Figure 1.2 Scale representing the number of cells required per construct to ...
Figure 1.3 Overview of various clinical and pre‐clinical imaging techniques....
Figure 1.4 Influence of various printing parameters in cell viability.
Figure 1.5 Bioprinting of a vascular construct: (A‐a) structural feature of ...
Figure 1.6 Bioprinted constructs for innervation: (a) Confocal microscopic i...
Chapter 2
Figure 2.1 Optical photographs (a) and scanning electron microscope (SEM) im...
Figure 2.2 Transmission electron microscope (TEM) analysis for 1Cu‐MBG (a) a...
Figure 2.3 SEM images of the non‐doped and Mg‐doped β‐TCP surfaces: (a) afte...
Figure 2.4 The surface topography of TCP bioceramics induced macrophage pola...
Figure 2.5 Calcium phosphate ceramics with different phase compositions regu...
Figure 2.6
In vivo
angiogenesis (a) and new bone formation (b) of the lotus ...
Chapter 3
Figure 3.1 (a) Illustration of fabricating nSi‐incorporated GelMA hydrogels ...
Figure 3.2 (a) Illustration of dual‐channel bioink system for 3D bioprinting...
Figure 3.3 (a) 3D printing of PNAGA20%‐clay scaffolds and resistance to comp...
Figure 3.4 The fabrication process of melt‐plotted PCL struts and inserting ...
Figure 3.5 (a–c) Fabrication of different scaffolds. (a) 3D plotting of alg/...
Figure 3.6 (a) Material composition of PCaP pastes. (b) Fabricating process ...
Figure 3.7 (a) Fabrication of 3D‐printed hyperelastic bone. (i) HA/PLGA liqu...
Figure 3.8 (a) Fabrication process of a triphasic scaffold: (i) generating a...
Figure 3.9 (a) Illustration of the IOP system. (b) 3D‐bioprinted MTU constru...
Figure 3.10 (a) (i) Microfluidic 3D bioprinting system. (ii) Microfluidic pr...
Figure 3.11 (a) (i) Schematic showing the fabrication process of 3D HC‐PMNFs...
Figure 3.12 (a) Fabrication of ECM/GelMA/exosome scaffolds for osteochondral...
Chapter 4
Figure 4.1 MSCs have been found in different tissues and organs such as bone...
Figure 4.2 The derivation and differentiation of osteoblasts, osteocytes, an...
Figure 4.3 Summary of the derivation and application of MSCs in orthopedics....
Chapter 5
Figure 5.1 Typical scanning electron microscopy (SEM) image of electrospun n...
Figure 5.2 Schematic illustration showing the setups of (a) traditional elec...
Figure 5.3 Schematic illustration of the setups of (a–c) conjugated electros...
Figure 5.4 Schematic illustration showing special spinnerets: (a) triaxial (...
Figure 5.5 SEM images showing (a) the PLA nanofibers coated with fibronectin...
Figure 5.6 Schematic illustration of the musculoskeletal system.
Figure 5.7 Evaluation of
in vivo
bone repair. (a) Schematic showing the oper...
Figure 5.8 (a) Stereomicroscope photographs of
ex vivo
incubation with the n...
Figure 5.9 (a) Schematic illustration showing the surgical procedure to indu...
Figure 5.10 (a) Gross evaluation, (b) H&E, and (c) Masson staining of the ra...
Figure 5.11 (a) Fabrication of a scaffold with random‐aligned‐random structu...
Chapter 6
Figure 6.1 (a) The overall structure of synovial joint system.(b) The re...
Figure 6.2 (a) The schematic structure formed by the biomacromolecules on ar...
Figure 6.3 (a) Atomic force microscopy (AFM) of lubricin coated onto highly ...
Figure 6.4 (a) The schematic diagram showing the pendulum friction tester em...
Figure 6.5 (a) Topographic AFM images of the surface of (i) bare UHMWPE and ...
Figure 6.6 (a) The design of MSNs@lip nanoparticles with enhanced lubricatio...
Figure 6.7 (a) The preparation of the PSPMA‐
g
‐HSNPs nanoparticles with a cor...
Figure 6.8 (a) The development of a self‐powered triboelectric nanogenerator...
Chapter 7
Figure 7.1 Representative examples of point‐of‐care technology (
Figure 7.2 (a) The overall view of a microfluidic device for DNA analysis. M...
Figure 7.3 A representative example of a microfluidic organ‐on‐a‐chip. It co...
Figure 7.4 A cross‐linking reaction to develop PDMS elastomer.
Figure 7.5 Schematics of soft lithography to fabricate a PDMS‐based microflu...
Figure 7.6 Schematics of a microvalve operation by (a) pneumatic and (b) ele...
Figure 7.7 Schematics of micropump operations: (a) check‐valve micropump and...
Figure 7.8 Schematics of various channel designs for passive micromixing: (a...
Figure 7.9 Examples of (a) flow‐based and (b) diffusion‐based microfluidic g...
Figure 7.10 Schematics of fabricating a microfluidic device with a tissue ba...
Figure 7.11 Hydrogel‐integrated organ‐on‐a‐chip. (a) A hydrogel‐based vascul...
Figure 7.12 Various methods of applying external mechanical stimuli to organ...
Figure 7.13 Microfluidic microvascular network. (a, b) Two channels are lade...
Figure 7.14 A microfluidic angiogenesis chip. Human microvascular endothelia...
Figure 7.15 Hydroxyapatite (HA)‐based ceramic bone‐on‐a‐chip. (a) HA‐ceramic...
Figure 7.16 (a) A highly porous scaffold, developed by a polymerized high in...
Figure 7.17 A schematic illustration of an organ‐on‐a‐chip platform to devel...
Figure 7.18 (a) MSCs are first cultured within a HA‐coated zirconia scaffold...
Figure 7.19 (a) Osteoblasts are cultured in a microfluidic chamber with a di...
Chapter 8
Figure 8.1 Bioactive glasses with various compositions processed as bulk, po...
Figure 8.2 SEM images and energy‐dispersive X‐ray spectroscopy (
Figure 8.3 Chemical structure of PGA, PLA, PLGA, and the enantiomers D‐ and
Figure 8.4 Structure of poly(ɛ‐caprolactone) (PCL).
Figure 8.5 Schematic representation of a composite material (a) and a hybrid...
Figure 8.6 Overview of biological responses to ionic dissolution products of...
Figure 8.7 (a) Schematic representation (inspired from Mahony et al. [18]) a...
Figure 8.8 Structure of different sol–gel precursors used in hybrid material...
Chapter 9
Figure 9.1 The process of 3D printing. (a) Importing the 3D model. (b) Slici...
Figure 9.2 3D printing tissue engineering scaffolds made of different materi...
Figure 9.3 The
in situ
3D print based on microextrusion print. (a) Repair th...
Chapter 10
Figure 10.1 Osteoclasts and osteoblasts: osteoclasts are derived from hemato...
Figure 10.2 Healing process of bone fracture. (a) Inflammatory phase, (b) so...
Figure 10.3 0 P, 0.1 P, and 0.3 P represent the addition from 0%, 0.1%, and ...
Figure 10.4 (a–c), (d–f), and (g–i) are the images obtained when the elastic...
Figure 10.5 Preparation and working principle of antitumor Se‐HANs nanoparti...
Figure 10.6 Schematic illustration of the fabrication of Ti
3
C
2
‐BG scaffold, ...
Figure 10.7 Schematic illustration of fabricating a bifunctional scaffold. (...
Chapter 11
Figure 11.1 The elastic bionic device for distal tibiofibular syndesmosis (a...
Figure 11.2 Schematic diagrams showing the main procedures for fixation of t...
Figure 11.3 A male patient sustained left DTS, who were treated using the el...
Figure 11.4 The suspended bridge structure of the posterior pelvic ring: (a)...
Figure 11.5 The photograph of the minimally invasive adjustable plate for th...
Figure 11.6 The schematic diagrams showing the reduction ability of MIAP in ...
Figure 11.7 A 15 year‐old boy sustained compressed sacral fractures on the r...
Figure 11.8 The schematic diagrams of a bionic dynamic hip screw for intertr...
Figure 11.9 The schematic diagrams of bionic implants for tibial plateau fra...
Figure 11.10 The bionic Gamma nail for intertrochanteric fracture of the fem...
Figure 11.11 The bionic screw with holes of different size: (a) the design d...
Figure 11.12 The bionic screw was inserted into the femoral neck of the shee...
Figure 11.13 Comparing biomechanical characters among six types of bionic im...
Figure 11.14 Comparing biomechanical effect of different‐sized circular hole...
Figure 11.15 The bionic calcaneal plate and the calcaneal model fixed with t...
Figure 11.16 (a) Higher magnification of the MC fibrils. The inset shows the...
Chapter 12
Figure 12.1 Anatomy schematic and histology of articular cartilage.
Figure 12.2 OARSI grade system for evaluating osteochondral samples from hum...
Figure 12.3 OARSI scoring system for evaluating mouse knee joint.
Figure 12.4 Repair strategies for cartilage defects. The currently used repa...
Figure 12.5 Tissue engineering approaches for articular cartilage repair. IP...
Figure 12.6 Overview of gene therapy protocol for cartilage repair.
Chapter 13
Figure 13.1 Osteochondral tissue structure. Structural/spatial organization ...
Figure 13.2 Current 3D printing techniques including laser‐based, inkjet‐bas...
Chapter 14
Figure 14.1 Schematic representation highlighting the hallmarks of human dis...
Figure 14.2 Treatment plan for biological intervertebral disc repair. As dis...
Figure 14.3 Potential mechanisms underlying mesenchymal stem cell‐mediated r...
Figure 14.4 Schematic presentation of gene therapy flow. A new gene is inser...
Figure 14.5 Anatomical tissue engineering total disc replacement (TE‐TDR...
Chapter 15
Figure 15.1 Schematic representation of the skin structure.
Figure 15.2 The various stages of skin wounds and wound healing. (a) Inflamm...
Figure 15.3 Some examples of skin scaffolds. (A) Epidermal substitutes; (B) ...
Figure 15.4 Commercially available skin substitutes.
Figure 15.5 Tissue‐engineered skin substitutes. (a) Acellular: i. Karoderm, ...
Chapter 16
Figure 16.1 Illustration of techniques for biofabrication of vascular and va...
Figure 16.2 Inkjet 3D printing. (a) Schematic of the printing process using ...
Figure 16.3 Extrusion bioprinting. (a) Fabrication of a 3D alginate structur...
Figure 16.4 Examples of LIFT and DLP bioprinting. (a) Illustration of a LIFT...
Figure 16.5 Micromodule assembly. (a) Assessment of the viability of HUVEC‐c...
Figure 16.6 Electrospinning nanofibrous vascular scaffolds. (a) Schematic di...
Chapter 17
Figure 17.1 Biological interactions of the “cells–material–blood supply trin...
Figure 17.2 Histological analysis (HE, ×100) of a tube‐shaped bioceramic (a)...
Figure 17.3 Scaffolds of identical interconnection size (120 μm) and differe...
Figure 17.4 Histological results at four weeks: 300–400 (a), 400–500 (b), 50...
Figure 17.5 Positive correlation was observed between the pore size and vasc...
Figure 17.6 SEM pictures of porous bioceramics with identical pore size (300...
Figure 17.7 Histological results at four weeks: 70 (a), 100 (b), 120 (c), 15...
Figure 17.8 Positive correlation was observed between the interconnection si...
Figure 17.9 Influence of the pore size on vascularization.
Figure 17.10 3D reconstructions of neovascularization (a–f) and statistical ...
Figure 17.11 Micro‐CT scans of vascularization in the scaffold. Reparative a...
Figure 17.12 Depth of directed vascularization (black) and growth rate (blue...
Figure 17.13 The principle of the procedure is to restore the blood supply o...
Figure 17.14 Description of the surgical procedure. (a) Positioning, (b) bon...
Figure 17.15 42‐year‐old male patient with ARCO stage IIIA osteonecrosis of ...
Chapter 19
Figure 19.1 Rotator cuff anatomy and the involved tendons including supraspi...
Figure 19.2 Illustration of rotator cuff tendon tears.
Figure 19.3 Shoulder disability resulted by rotator cuff tears.
Figure 19.4 Histological picture of the rabbit supraspinatus tendon‐to‐bone ...
Figure 19.5 Structure and composition of fibrocartilaginous entheses. Fibroc...
Figure 19.6 The structure of tendon fibers changes before attaching to bone....
Figure 19.7 Fundamental structural and molecular components of the enthesis....
Figure 19.8 Schematic illustration of fabrication of G‐P/C composite film by...
Figure 19.9 A schematic drawing of the lithium‐containing mesoporous silica ...
Figure 19.10 Cell and co‐culture strategies for the generation of a tendon/l...
Figure 19.11 Schematic diagram illustrating the formation of PCL/Pluronic F1...
Chapter 20
Figure 20.1 Tendons link muscles to bones and are fixed to bones by the enth...
Figure 20.2 The tendon has a multi‐unit hierarchical structure composed of c...
Chapter 21
Figure 21.1 Illustration of strategies to rebalance the postinjury microenvi...
Figure 21.2 Illustration of pathophysiological compartments of an injured sp...
Figure 21.3 The illustration demonstrates the structure of the peripheral ne...
Figure 21.4 The 2019 revision of the International Standards for Neurologica...
Guide
Cover
Table of Contents
Title Page
Copyright
Foreword from Prof. Changsheng Liu
Foreword from Prof. Yingze Zhang
Foreword from Prof. Lianfu Deng
Foreword from Prof. Cato T. Laurencin
Preface
Begin Reading
Index
End User License Agreement
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Biofabrication for Orthopedics
Methods, Techniques, and Applications
Edited byWenguo CuiXin ZhaoShen Liu
Volume 1
Biofabrication for Orthopedics
Methods, Techniques, and Applications
Edited byWenguo CuiXin ZhaoShen Liu
Volume 2
Editors
Prof. Wenguo CuiShanghai Jiao Tong University School of MedicineShanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital197 Ruijin 2nd Road200025 ShanghaiChina
Prof. Xin ZhaoHong Kong Polytechnic UniversityDepartment of Biomedical Engineering11 Yok Choi Road, Hung Hom999077 Hong KongHong Kong
Prof. Shen LiuShanghai Jiao Tong UniversityAffiliated Sixth People's Hospital600 Yishan RoadDepartment of Orthopaedics200233 ShanghaiChina
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Print ISBN: 978‐3‐527‐35169‐5ePDF ISBN: 978‐3‐527‐83136‐4ePub ISBN: 978‐3‐527‐83135‐7oBook ISBN: 978‐3‐527‐83137‐1
Editors
Prof. Wenguo CuiShanghai Jiao Tong University School of MedicineShanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital197 Ruijin 2nd Road200025 ShanghaiChina
Prof. Xin ZhaoHong Kong Polytechnic UniversityDepartment of Biomedical Engineering11 Yok Choi Road, Hung Hom999077 Hong KongHong Kong
Prof. Shen LiuShanghai Jiao Tong UniversityAffiliated Sixth People's Hospital600 Yishan RoadDepartment of Orthopaedics200233 ShanghaiChina
Cover Image: © SciePro/Adobe Stock Photos
All books published by WILEY‐VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
Library of Congress Card No.: applied for
British Library Cataloguing‐in‐Publication DataA catalogue record for this book is available from the British Library.
Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.
© 2023 WILEY‐VCH GmbH, Boschstraße. 12, 69469 Weinheim, Germany
All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.
Print ISBN: 978‐3‐527‐35170‐1ePDF ISBN: 978‐3‐527‐83136‐4ePub ISBN: 978‐3‐527‐83135‐7oBook ISBN: 978‐3‐527‐83137‐1
Foreword from Prof. Changsheng Liu
I would like to thank Profs Wenguo Cui, Xin Zhao, and Shen Liu for inviting me to write this foreword. I am honored to take part in the knowledge exchange of our scientific culture, as well as to promote training of our students and professionals.
With the rapid development of biomaterials and biofabrication technologies, a variety of biomaterials have been made for the repair and regeneration of bone, muscle, tendon, and other orthopedic tissues and organs. This book focuses on the current state of biofabrication technologies and materials in orthopedics biomedical applications. The various highlights of this book include a comprehensive analysis of different biofabrication methods for constructing relevant biomaterials in the orthopedics field, with an emphasis on the recent developments of technologies involving 3D printing, bioceramic, electrospinning, microfluidics, bioactive glass, etc. A detailed look into these biofabrication techniques using different biomaterials is also included in terms of functional performance, advantages, and disadvantages for repairing and regeneration in orthopedics, of which the choices of biomaterials are especially critical since their applications must be based on a thorough knowledge of the anatomy and physiology of the bone, muscle, and adjacent tissue. With the content being organized clearly, practically, rigorously, and most importantly, up to date with current knowledge, this review will therefore provide the research community a reference source for current approaches to biomaterials and scaffold preparation in orthopedics, as well as to reinforce our readers' understanding of materials' biomedical applications in orthopedics.
In essence, this book is clear and well written in a way that provides highly useful and relevant content to support trained orthopedic doctors and biomaterial researchers. This helps give the readers the basis of the preparation of a variety of biomaterials and thus enhance the understanding of their application in orthopedics. Through this book, the authors have faith that the readers and researchers can generate next‐generation biomaterials for orthopedic applications.
Changsheng Liu
East China University of Scienceand Technology, P.R. China
Foreword from Prof. Yingze Zhang
In the past decades, traditional orthopedic metal implants such as plates and rivets have benefited many patients with orthopedic diseases. However, problems such as mechanical failure and poor efficacy always exist, which need to be solved through innovation. Nowadays, interdisciplinary convergence and cross‐border integration of several technologies are becoming the norm and will continue to give birth to the forefront of new disciplines. Thanks to the development of tissue engineering and regenerative medicine, a large number of new materials and technologies with great application prospects in orthopedic medicine have emerged, providing new opportunities for the diagnosis and treatment of orthopedic diseases.
This book systematically demonstrates the widely popular and eye‐catching biomaterials and biofabrication technologies, explains in detail their advantages and disadvantages in orthopedics, and lists their applications in the repair of bone, muscle, ligament, tendon, and other orthopedic organs.
Each chapter of this book emphasizes the impact of advanced materials and biofabrication technologies in the field of orthopedics, including how biofabrication affects all substances used in bone implants (from 3D printing to electrospinning and microfluidic technology). One of the highlights of this book is apparently to cover the most innovative biomaterial manufacturing technologies and emphasizes the safety of biofabrication that we have not fully understood and need to develop solutions. It also provides concise reasons on why we should consider using these materials to complete the regeneration and repair of orthopedic systems, discussing in‐depth beyond the typical trial‐and‐error thinking of traditional orthopedics.
The editors and authors of this book hope to enrich readers and researchers in the field of orthopedics, orthopedic biomaterials, and their clinical applications, and in my opinion, this book is certainly a must‐have for all those who want to create new solutions to the most stubborn problems in orthopedics, so that we can improve the quality of life for patients of implants with novel biofabrication technologies. We believe that new orthopedic biofabrication technologies for bone tissue regeneration and a better understanding of the interface between biomaterials and adjacent tissues will be an important part of orthopedic biomaterials and implants in the future for better orthopedic surgery.
Yingze Zhang
Department of Orthopedic SurgeryThird Hospital of HebeiMedical University DirectorNHC Key Laboratoryof Intelligent OrthopaedicEquipment, ShijiazhuangP.R. China
Foreword from Prof. Lianfu Deng
With the rapid development of medical science and engineering technology, the field of orthopedics has also made great progress. In recent years, biomaterial implants have been widely used in the replacement treatment or adjunctive therapy of injured bones to replace, support localization, or repair human bones, joints, and soft tissues. The clinical demand for orthopedic implanted medical devices has been maintaining a rapid growth rate. However, due to the differences in disease or injury types, the demand for personalized design and fabrication of biomaterials and biomaterials with specific functions is also increasing. This also greatly promoted the development of orthopedic materials through biofabrication technology.
The continuous innovation and development of biomaterial fabrication technologies (3D (three‐dimensional) bioprinting, electrospinning, and microfluidic) have improved the utilization of biomaterials, including the fabrication of complex 3D structures, the improvement of biomaterial interface and cell interaction, and the development of controlled drug‐release systems. The development and biofabrication of advanced biomaterials in orthopedics field covers the interdisciplinary study of materialogy, tissue engineering and regenerative medicine, cell and molecular biology, and clinical medicine. The biofabrication techniques bridge basic research and clinical treatment, help to accelerate the orthopedic basic scientific research to the engineering application of the industrialization process, and promote the development of targeted treatment strategies for different orthopedics diseases or injuries. It is meaningful to advance the development progress of translational medicine.
It is timely to compile this book on advanced fabrication technology of biomaterials and its application in orthopedics. This book summarizes the latest scientific research progress and development trend of orthopedics worldwide, aiming to track the frontier of the discipline, introduce advanced theories and technologies, and promote the development of orthopedics and orthopedics technology. This book will help doctors, researchers, and students of medical specialty to have a good command of the design, fabrication, and application of biomaterials as well as the regulatory mechanism of bone regeneration process and better understand the development direction of biological fabrication and orthopedic technology.
Lianfu Deng
Shanghai Key Laboratoryfor Prevention and Treatmentof Bone and Joint DiseasesShanghai Institute ofTraumatology and OrthopaedicsRuijin Hospital, Shanghai Jiao TongUniversity School of MedicineP.R. China
Foreword from Prof. Cato T. Laurencin
It is always a great privilege to be invited to write a foreword for a book. Moreover, when the book enlarges our scientific knowledge and viewpoints while promoting the training of our students and professionals, it is even more welcome. I am therefore more than happy to provide my insights regarding such books.
The convergence of the life, physical, and engineering sciences has led to the creation of a new multidisciplinary field, which I have termed as “regenerative engineering.” Orthopedic surgery is a prominent field that stands to gain from the insights of regenerative engineering. In particular, biofabrication techniques developed in this field applying the principles of regenerative engineering have the potential of bringing revolutionary treatments to clinical practice. This book summarizes important aspects of biofabrication techniques for orthopedic surgery and offers valuable information of state‐of‐the‐art technological advancements that can ultimately become a practical toolbox for physicians, scientists, and engineers. While traditional orthopedic surgery books cover conventional strategies, this book focuses on newer biological strategies such as bioprinting, stem‐cell therapy, and organ‐on‐a‐chip technology. The chapters encourage readers to examine and embrace novel technologies to address clinical challenges. The content is well organized while covering a wide range of related fields. The knowledge and information provided by all the contributors are up to date, covering comprehensively technological aspects as well as clinical applications involved in orthopedic surgery practice.
The editors of this book, Profs Wenguo Cui, Xin Zhao, and Shen Liu, have assembled an excellent team and have created an important contribution to our field. The contributors to this book are respected scholars and professionals that come from a broad background including orthopedic surgery, biomedical engineering, stem‐cell biology, and physics. This allows the book to have insights regarding the current status and future trends of this field.
Scientific books must evolve to capture important aspects of the corresponding fields. This book is published at the right time when many exciting new biofabrication technologies have arisen, many of them inspired by the field of regenerative engineering. I congratulate again the editors of the book. This well‐organized contribution to the world's literature will be relevant to scientists, engineers, and clinicians everywhere.
Cato T. Laurencin, MD, PhD
Member, National Academy of Science/National Academy of EngineeringAlbert and Wilda Van Dusen DistinguishedProfessor of Orthopaedic SurgeryProfessor of Chemical andBiomolecular EngineeringProfessor of Materials Scienceand EngineeringProfessor of Biomedical EngineeringDirector, The Raymond and Beverly SacklerCenter for Biomedical, Biological, Physicaland Engineering SciencesChief Executive OfficerThe Connecticut Convergence Institutefor Translation in Regenerative EngineeringThe University of Connecticut
Preface
Wenguo Cui Xin Zhao Shen Liu
Bone, as one of the most essential organs in the body, not only supports the stability of body along with protection of other organs, but also provides hematopoietic function and stores minerals such as calcium and phosphorus. Unfortunately, when some damages/diseases, such as fracture, osteoarthritis, and osteoporosis, appear in the bones, these functions will be disrupted, leading to the systemic responses as seen clinically. Researchers are therefore proposing to develop techniques to remodel the damaged/diseased bone functions. Last decades, biofabrication techniques, including three‐dimension (3D) bioprinting, 3D printing, electrospinning, microfluidics, and stem‐cell therapy, have been widely applied in tissue regeneration. Some products of these biofabrication techniques were even commercialized, such as Absorb GT1 and XinSorb. Biofabrication for Orthopedics – Special Topic in Wiley mainly focuses on the development of biofabrication and applications in orthopedics, comprising 20 chapters in total, as detailed below.
Areas Covered in the Special Topic
The book starts with the two popular biofabrication techniques in the recent decades, namely, translational 3D bioprinting and 3D printing, which are comprehensively reviewed by Xiao and colleagues in the choice of bioink, cell types, the remodeling and maturation of bioprinting scaffolds, and by Zhang and colleagues in the choice of 3D printing polymers. Bioceramics, as a class of inorganic and non‐metallic materials, is introduced by Wu and colleagues in the preparation of various bioceramics, along with the potential applications for the hard tissue repair. Additionally, Massera and colleagues provide an overview about the synthesis and application of different bioactive glasses. In addition to the bioactive scaffolds, the mesenchymal‐stem‐cells‐derived extracellular vesicles and exosomes can also be regarded as biofabrications, which are thoroughly discussed by Jiang and colleagues. With the use of advanced biomaterials, two common techniques, electrospinning and microfluidics, are also reported by Wu and colleagues, and Cha and colleagues, respectively.
The application of 3D printing in orthopedics, including, but not limited to, bone engineering and cartilage engineering, is provided by Jiang and colleagues. Implantation and fixation are important processes in orthopedics. Laurencin and colleagues review implants that provide structural support and regulate stem‐cell behaviors, while Chen and colleagues review the fixation of distal tibiofibular syndesmosis and intertrochanteric fracture of the femur. Besides bones, cartilages are also discussed starting with pathology cartilage injuries and clinical magnetic resonance imaging assessments that are introduced by Wang, followed by the review by Li and colleagues detailing scaffolds and cell‐derived products for the cartilage regeneration. Additionally, intervertebral disc, as another special organ, is also reviewed by Cao and colleagues in terms of its current understanding and its repair using biofabrication‐based treatments. Moreover, Zhang and colleagues also provide a comprehensive overview on joint lubrication.
In the process of bone regeneration, angiogenesis plays a critical role in accelerating regeneration. In this regard, Lu and colleagues thoroughly describe how biofabrication guided angiogenesis in controlling the pore diameter and interconnection diameter. Furthermore, Wang and colleagues review in detail the applications of different biofabrication techniques in vascularization such as bioprinting, electrospinning, or microfluidics. Since bone injuries usually are accompanied by skin, muscle, nerve, and tendon injuries, Wang and colleagues introduce various types of cells involved in the skin regeneration, and how the cell‐derived products regulate the repairing. Fan and colleagues additionally review the functions of muscles, the influences of volumetric muscle loss (VML), and how it can be repaired via different biofabrication techniques. Nerve regeneration including peripheral nerve regeneration, spinal cord regeneration, and the clinical applications of nerve conduit are reviewed by Qian and colleagues. As a tendon complex, He and colleagues introduce the rotator cuff under clinical use and show how biofabrications regulate rotator cuff repairing.
In summary, this book provides a comprehensive review of novel biofabrication techniques including 3D printing, electrospinning, microfluidics, exosomes, and more for applications in bone and bone‐related regeneration. We believe this book can serve as the definitive reference of the latest technologies that could inspire medical practitioners and translational researchers to improve the quality of life of patients, whether it is to transform clinical procedures in present or to propose novel procedures of improved biomaterials in the near future.
27 October 2021
Wenguo Cui
Department of OrthopaedicsShanghai Key Laboratoryfor Prevention and Treatmentof Bone and Joint DiseasesShanghai Institute of Traumatologyand Orthopaedics, Ruijin HospitalShanghai Jiao Tong University Schoolof Medicine, 197 Ruijin 2nd RoadShanghai 200025P.R. China
Xin Zhao
Department of Biomedical Engineeringthe Hong Kong Polytechnic UniversityHung Hom, Hong KongP.R. China
Shen Liu
Department of OrthopaedicsShanghai Jiao Tong UniversityAffiliated Sixth People's Hospital600 Yishan Road, Shanghai 200233P.R. China
Part IBiofabrication Techniques
1Current Progress and Technological Challenges in Translational 3D Bioprinting
Greeshma Ratheesh1, Natividad G. Cerezo2, Weidong Gao1, Jayanti Mendhi1, Prashant Sonar3,4, and Yin Xiao1,5
1Queensland University of Technology, Institute of Health and Biomedical Innovation, Centre of Biomedical Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia
2The University of Queensland (UQ), School of Dentistry, 288 Herston Road, Herston, Brisbane, QLD, 4006, Australia
3Queensland University of Technology, School of Chemistry and Physics, 2 George Street, Brisbane, Brisbane, QLD, 4000, Australia
4Queensland University of Technology, Centre for Materials Science, 2 George Street, Brisbane, Brisbane, QLD, 4059, Australia
5Queensland University of Technology, Australia‐China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), 60 Musk Avenue, Kelvin Grove, Brisbane, QLD, 4059, Australia
1.1 Introduction
In the field of tissue engineering and regenerative medicine, bioprinting has emerged as an advanced tool that enables the creation of 3D functional tissue models with tailored biological and mechanical properties. It is defined as the application of scientific postulates to the design, construction, modification, and growth of living tissues using suitable biomaterials, cells, and growth factors, alone or in combination [1–3]. Usually, it is referred to as the use of computer‐aided technique to pattern and assemble living cells and biomaterials in a two‐dimensional or three‐dimensional orientation by printing successive layers of materials. This process allows the production of bioengineered tissue structures that could serve in tissue engineering and regenerative medicine, pharmacokinetics, and cell biology studies [4]. The approach helps to eliminate problems such as donor site scarcity, immune rejection, and pathogen transfer. Cells such as osteoblasts, chondrocytes, and mesenchymal stem cells obtained from hard and soft tissues proliferate on printed scaffolds that are biodegradable and are eventually resorbed as the tissue construct grows [4]. Scaffold properties, such as porosity, interconnectivity, roughness, etc., play an essential role in the cell proliferation and differentiation [5]. It has been demonstrated that the interconnected pores with size between 0.100 and 1 mm, can facilitate the tissue regeneration, angiogenesis, nutrient transfer, oxygen supply, and withdrawal of metabolic wastes [6]. Other parameters such as scaffold topography, including the composition and the microstructure, aid in cellular adhesion, spreading, proliferation, and cytoskeletal function [7].
Figure 1.1 Steps in bioprinting process. (1) Imaging of the damaged tissue; (2) design approach using biomimicry, self‐assembly, and mini‐tissue building blocks; (3) choice of material; (4) choice of cell; (5) choice of desired printing technique; and (6) maturation and application of the printed tissue.
Source: Xing et al. [24]. Reprinted with permission of MDPI/CC BY 4.0.
One of the advanced methods in scaffold fabrication is the bioprinting process. Unlike other scaffold fabrication methods, the material used in bioprinting is living cells that are incorporated into soft printable gel precursor solution, commonly referred to as bioink [8–10]. Bioink is defined as the material that has the ability to mimic the extracellular matrix (ECM) environment in order to enhance the proliferation and differentiation of cells [10–22]. The bioink could be natural, synthetic, or a combination of both, which guarantees cell viability and printability. The rheological properties of an ideal bioink should maintain the scaffold structure; hence, the viscosity of the bio‐ink and/or its capacity for rapid crosslinking is central to the success of the printing [23]. The process of bioprinting using these bioinks helps to encapsulate and deliver one or several cell types in a precise manner and enables the manufacturing of complex structures that could integrate into living tissues.
The process of bioprinting as illustrated in Figure 1.1 involves a series of steps, namely, imaging of the defective site, designing using a computer‐aided design, followed by the selection of an appropriate material and cells, and finally toward the printing. The final success of the construct is determined by the post‐processing, which involves regular monitoring with an optimum supply of nutrient and oxygen in the printed construct [25]. The complexity and versatility of this technique guarantee a wide range of applications such as regeneration of tissues like bone [26], cartilage [27], liver [28], and skin [29]. The fabrication methods have been improved by protein coating [30], cell deposition, and drug delivery [31, 32], and the fabricated tissues also assist in studying tumor growth [33], vascular network formation [34, 35], and understanding of stem cell differentiation [36, 37]. This chapter focuses on the current progress and technological challenges in the bioprinting process toward tissue regeneration and present the knowledge gaps in adopting this technology.
1.2 Challenges in the 3D Bioprinting Process
The successful fabrication of functional tissue or organ depends on the advancement in three types of technology, namely, the manufacturing technology, cell technology, and technology for in vivo integration [38]. Although the field of 3D bioprinting has demonstrated the remarkable potential for future development in the field of tissue and organ printing, there are several challenges that must be overcome to reach the stage of translation to a biological platform. Some of the critical challenges in the field of 3D bioprinting have been discussed in the following sections.
1.2.1 Manufacturing Challenges
1.2.1.1 Choice of Bioink
Hydrogels are ideal materials for the 3D bioprinting process because of the tunable physicochemical properties and the ability to mimic . The ability of hydrogels to hold high water content that allows cell migration, nutrient/oxygen transfer, and waste removal makes it an important candidate for 3D bioprinting. There are a variety of hydrogels used for the bioprinting process such as alginate, collagen I, methacrylated gelatin, and poly(ethylene glycol) (PEG) [39–43]. Hydrogels are either from a natural source or artificially synthesized or a combination of different materials. Compared to the natural hydrogel, the synthetic materials that possess the ability to modify the chemical structure show more advantages [44, 45]. However, there are certain drawbacks in the use of such hydrogels, such as the mechanical strength, printing resolution, and maintaining the shape of the printed construct [46–48]. The mechanical stability of the scaffold printed using such bioink still remains a critical challenge. In recent times, bioactive or composite materials are developed with the insight of improving the mechanical stability or tissue interaction [49]. The 3D printable bioink can be extended by creating certain chemical modifications on the biomaterials [50–52]. For instance, the multi‐armed oligomers/polymers or branched polymers can be acrylated or methacrylated to produce macromeres or prepolymers that can be photocrosslinked. This kind of polymer that is photocrosslinked has high gel content with high degree of crosslinking [51]. On the other hand, in order to achieve high mechanical strength and biological activity, scaffolds are fabricated by combining a biodegradable polymer or other biomaterials which provide the required mechanical stability and a functional bioink loaded with cells for imparting an increased biological activity on the resulting construct [53–55]. The incorporation of such substitutes not only improves the mechanical property but also has an influence on the improved porosity. For example, in a study demonstrated by Dandoy et al. 2011, a silica shell was introduced around alginate‐based hydrogel beads by in situ silicic acid sol–gel transition by polycations. The resulting composite hydrogel possesses improved mechanical strength and chemical stability. They also revealed regulated porosity to govern mass exchange between the external environment and the interior hydrogel in order to achieve controlled paracrine for cell therapy [56].
Yet another important characteristics that bioink should possess is the ability to improve the biomimetic property that regulates the cell behavior [57, 58]. The development of an optimal biomaterial that possesses a suitable microenvironment for cell response with optimal mechanical properties and printability remains a critical challenge in regenerative engineering. An ideal bioink should possess the ability to improve the biomimetic properties and thereby regulate the cell behavior [57, 58]. The biological properties of bioink can be enhanced by the use of certain growth factors or cytokines that regulate cell proliferation and differentiation by providing suitable biochemical and physiochemical factors for tissue regeneration. The material printability and cytocompatibility are currently the most important criteria of bioprinting process. For example, Kristin et al. 2015 developed a novel bioink using spider silk protein. The group suggests that such kind of bioink can be used without any crosslinking agent or thickeners for increasing the mechanical stability of the scaffold, and the use of cell‐binding motif to the silk protein for enhancing the tunability of cell–material interactions [59].
1.2.1.2 Cell Selection and Optimization
Most of the tissues or organs are made up of multiple types of cells that serve different functions such as structural support, role in vascularization, or provide a suitable niche for the differentiation of stem cells. The choice of cells is highly dependent on the targeted tissue that is to be regenerated. The careful selection of cells should fulfill their physiological state in vivo and maintain the function under optimum conditions [10, 60]. The type of cells selected should proliferate in a controlled fashion; in other words, less proliferation can lead to the loss of viability, whereas high proliferation leads to hyperplasia or possible apoptosis. Furthermore, the number of cells incorporated in a specific construct is also a crucial parameter that varies with the type of tissue. For example, the estimated number of cells per gram of liver tissue is 1.3 × 108 cells. Hence, it is necessary to replicate this density during the bioprinting process [61]. Studies have reported that the minimum therapeutic threshold in order to serve the solid organ function is 1–10 billion cells [62, 63] (Figure 1.2). However, the cell content depends on the type of the bioprinting process. Extrusion‐based bioprinting can fabricate constructs with high cell density (approximately 8000 cells in 300 μm diameter), and on the other hand, inkjet bioprinting/droplet‐based bioprinting can print with a lower cell density of <106 cells/ml [61].
Figure 1.2 Scale representing the number of cells required per construct to form a solid tissue construct.
Source: Miller [63] / Plos One / CC BY‐4.0.
The increase in cell density has both advantages and disadvantages. The higher cell density during the printing process will aid in cell–cell interaction and promote tissue regeneration. However, this can affect the printability due to the change in the viscosity of bioink, which in turn affects the cell distribution [64]. Moreover, cell density also plays a critical role in cell proliferation and cell–cell interactions. In a printed construct, the bioink normally mimics the role of ECM environment for cell support. Studies have proved that an increase in cell density elevates the remodeling process of ECM [65, 66]. It is always advisable to use a high cell density for a better cell proliferation; however, cell density should be carefully distributed in the fabricated tissues considering the fact that each organ has different cell densities in different areas of tissue structure; for instance, in pancreas, high density of beta cells is surrounded by other types of cells (Alpha, Delta, Epsilon, and F cells) at a lower cell density, indicating the various cell density in functional tissue structures [67]. All these parameters suggest that more research is still needed for a better understanding in the distribution of cells post‐bioprinting and maintaining the optimum cell density to that of the native organ.
1.2.1.3 Printing Resolution and Mechanical Stability
In addition to biocompatibility and biodegradability, an ideal bioink should possess certain physicochemical properties that improve the resolution and mechanical stability of the printed construct [68]. The printed construct must have the optimum mechanical stability and porous environment for cell migration, penetration, proliferation, and vascularity. The rigidity of the native tissue ranges from 0.2 to 15 000 kPa, depending on the kind of the tissue. Similarly, the shear stiffness value also has a broad range from 100 Pa to 20 kPa. A wide range of parameters such as the viscosity, crosslinking strength, temperature, and printing speed govern the mechanical properties of the bioprinted construct. The rheological and mechanical properties of bioink varies with the type of the printing process; for instance, extrusion‐based bioprinting uses a highly viscous material (3–6 × 108 mPa s); on the other hand, droplet‐based bioprinting uses a less viscous material (3.5–12 mPa s) [69]. This in turn influences the mechanical stability of the printed construct.
The printability and mechanical stability of the printed tissue or organ are highly dependent on the type of biomaterials used for printing. Paxton et al. 2017 suggested that assessment of printability of bioink is a two‐step process, firstly to check the ability of bioink to form a fiber for 3D construct fabrication and secondly to understand the rheological characteristics [70]. The rheological requirement for extrusion‐based printing is influenced by the concentration of materials used for printing. In general, a low‐viscous material is preferred so as to avoid the shear stress that can in turn influence the cell viability [71]. However, high viscosity or solidification is necessary to retain the shape and structure of the printed scaffold. The printing resolution of bioprinting can be improved by the thermogelation process on materials such as gelatin [71, 72]. Bioink such as PEG is less viscous that makes it difficult to maintain their shape after printing. In one of the recent studies, Ribeiro et al. 2017 developed an evaluation technique for shape fidelity by testing filament collapse and filament fusion on poloxamer 407 and PEG blend. The group demonstrated a simple theoretical model to relate the collapse of filament with the yield stress of the bioink [73], in which the deflection angle in each gap distance was calculated using the formula
where ρ is the material density, g is the gravitational acceleration, L is the distance from the edge of the pillar to the midpoint of the suspended filament, and σyield is the yield stress of the hydrogel. Although the theoretical model overestimates the defection angle, the slope of regression shows the same trend as the experimental ones. This is because the model considers only the gravitational force and the yield stress of the hydrogel.
Another important parameter that influences the mechanical property and shape fidelity of the construct is the time and temperature (for temperature‐sensitive bioink). For instance, gelatin‐based bioink suffers poor shape fidelity until the strategy of two‐step crosslinking is introduced. The two‐step crosslinking shows a better shape fidelity, in which the first step is the physical crosslinking (lowering the temperature), and the second is a chemical crosslinking [74]. Silke et al. 2014 demonstrated a two‐step crosslinking using gelatin and alginate. The gelatin was heated to 40 °C and dispensed onto a cooling plate maintained at 10 °C, which leads to immediate solidification of the gel. This gel was further crosslinked with CaCl2 solution to retain the shape of the construct [74]. GelMA (methacrylated gelatin) is another popular material that can be used for two‐step crosslinking, in which the second step is a photocrosslinking. The mechanical stability of such construct relies on the number of crosslinking moieties and the UV exposure time. Cristina et al. 2016 demonstrated that the elastic modulus of the construct increased with UV exposure time [75]. Furthermore, the photocrosslinking property is also reported to enhance the shape fidelity of the printed construct with a suitable supportive polymer [74]. The shape fidelity and printing resolution can be also improved by blending two different materials. For example, studies have shown that the incorporation of supportive polymer such as hyaluronic acid methacrylamide (HAMA) in GelMA improved the shape fidelity and mechanical stability [76, 77
