3D tissue modelling is an emerging field used for the investigation of disease mechanisms and drug development. The two key drivers of this upsurge in research lie in its potential to offer a way to reduce animal testing with respect to biotoxicity analysis, preferably on physiology recapitulated human tissues and, additionally, provides an alternative approach to regenerative medicine.
Integrating physics, chemistry, materials science, and stem cell and biomedical engineering, this book provides a complete foundation to this exciting, and interdisciplinary field. Beginning with the basic principles of 3D tissue modelling, the reader will find expert reviews on key fabrication technologies and processes, including microfluidics, microfabrication technology such as 3D bioprinting, and programming approaches to emulating human tissue complexity. The next stage introduces the reader to a range of materials used for 3D tissue modelling, from synthetic to natural materials, as well as the emerging field of tissue derived decellularized extracellular matrix (dECM). A whole host of critical applications are covered, with several chapters dedicated to hard and soft tissues, as well as focused reviews on the respiratory and central nervous system. Finally, the development of in vitro tissue models to screen drugs and study progression and etiologies of diseases, with particular attention paid to cancer, can be found.

Auszug. � Genehmigter Nachdruck. Alle Rechte vorbehalten.

Biofabrication and 3D Tissue Modeling

By Dong-Woo Cho

The Royal Society of Chemistry

Chapter 1 Microstereolithography Shangting You, Kathleen Miller and Shaochen Chen, 1, 
Chapter 2 Extrusion-based Bioprinting Mitchell Kuss and Bin Duan, 22, 
Chapter 3 Microfluidic Platforms for Biofabrication and 3D Tissue Modeling Minghao Nie and Shoji Takeuchi, 49, 
Chapter 4 Computational Design and Modeling of Linear and Nonlinear Elastic Tissue Engineering Scaffold Triply Periodic Minimal Surface (TPMS) Porous Architecture S. J. Hollister, 77, 
Chapter 5 Shear Thinning Hydrogel-based 3D Tissue Modelling Christopher D. Lindsay and Sarah C. Heilshorn, 94, 
Chapter 6 Polymers in Biofabrication and 3D Tissue Modelling Ferry P. W. Melchels, 119, 
Chapter 7 Decellularized Tissue Matrix-based 3D Tissue Modeling Sanskrita Das, Ge Gao, Jae Yeon Lee, Jinah Jang and Dong-Woo Cho, 148, 
Chapter 8 3D Tissue Modelling of the Central Nervous System Seokyoung Bang, Seung-Ryeol Lee and Noo Li Jeon, 171, 
Chapter 9 3D Tissue Modelling of Skeletal Muscle Tissue Marco Costantini, Stefano Testa, Chiara Rinoldi, Nehar Celikkin, Joanna Idaszek, Cristina Colosi, Andrea Barbetta, Cesare Gargioli and Wojciech Swigszkowski, 184, 
Chapter 10 3D Tissue Modelling of Orthopaedic Tissues Ramya Bojedla, Shibu Chameettachal and Falguni Pati, 216, 
Chapter 11 3D Tissue Modeling of Skin Tissue Jun-ho Heo, Kyungha Kim, Suhyun Park, Noehyun Myung and Hyun-wook Kang, 233, 
Chapter 12 3D Modeling of Hepatic Tissue Mary C. Regier and Kelly R. Stevens, 253, 
Chapter 13 Microphysiological Models of the Respiratory System Dongeun Huh, 279, 
Chapter 14 3D Tissue Model of Cancers Yong Hun Jung, Hyejin Park, Kyuhwan Na, Hyunho Kim, Jihoon Yang and Seok Chung, 294, 
Chapter 15 3D Tissue Models for Toxicology Gregor Skeldon, David C. Hay and Wenmiao Shu, 312, 
Chapter 16 Ethics of Using Human Cells/Tissues for 3D Tissue Models Jung Yeon Lim, Do Hyun Kim, Sun Hwa Park and Sung Won Kim, 329, 
Subject Index, 345,

CHAPTER 1

Microstereolithography

SHANGTING YOU, KATHLEEN MILLER AND SHAOCHEN CHEN

1.1 Introduction

Fabrication is a critical process in making materials into functional parts and devices. Traditional fabrication technologies such as machining and molding are commonly used in macro-scale three-dimensional (3D) fabrication. However, they are not adequate for microscale fabrication. Modern micro- and nanoscale fabrication technologies such as photolithography, soft lithography, electron beam lithography, focused ion beam lithography, dip-pen lithography, and atomic layer deposition, are often 2-dimentional (2D) in nature for thin film and surface patterning.

3D printing, as an additive free-form 3D fabrication technology, has achieved great commercial success in the past decade, because of its low cost, simplicity, and versatility. Microstereolithography is a light-assisted 3D free-form fabrication technology. This technology utilizes photosensitive materials, which can solidify upon ultraviolet (UV) or short wavelength visible light exposure. By spatially controlling the exposure dose, the desired 3D structure can be fabricated. This technology evolves in two directions. One, scanning-based microstereolithography, which provides the extremely fine resolution (sub-micron scale) but slow fabrication speed (e.g., hours). Two, projection-based microstereolithography, which provides both fine resolution (micron scale) and fast fabrication speed (e.g., seconds to minutes).

Microstereolithography is a powerful tool for biofabrication. It has successfully demonstrated its capability of fabricating a wide range of biomaterials such as hydrogels, proteins, and cell-laden materials. Both synthetic and natural materials can be used to print, each having different advantages for stability, mechanical properties, cytocompatibility, and printability. Material decisions must come from the eventual application for the printed structure, as even the choice of photoinitiator can greatly impact the print.

This chapter covers basic physical and chemical mechanisms in photopolymerization, materials, devices, and systems of microstereolithography. The photopolymerization mechanism is detailed in Section 2. Materials for microstereolithography are discussed in Section 3. Scanning-based microstereolithography, including single-photon polymerization microstereolithography, and two-photon polymerization nano-stereolithography, is detailed in Section 4. Projection-based microstereolithography, including liquid–air interface polymerization and liquid–substrate interface polymerization, is discussed in Section 5.

1.2 Photopolymerization

In this section, we will focus on photopolymerization, a technique most often used to crosslink liquid state monomers or oligomers into solid state long-chain polymers. Photopolymerization uses free radicals to initiate and crosslink strands within a monomer solution to form a solid hydrogel. When paired with microstereolithography techniques, various complex structures can be fabricated.

1.2.1 Step-growth Polymerization

Two of the main types of polymerization observed in hydrogel scaffolds are step-growth and free-radical polymerization. Although photopoylmerization methods use free radicals to polymerize structures, the kinetics of step-growth polymerization can describe some of the more unique polymerizations, and thus it is important to cover. Step-growth polymerization occurs when polymer chains grow in a stepwise fashion either by condensation reactions, in which water is removed, or when reactive end groups interact. When considering simple linear chain reactions, the mechanisms and rates of all polymerization steps can be assumed as equal. Moreover, the Carothers equation (eqn (1.1)) defines the level of completion of the step-growth polymerization

xn = 1/(1 - p) (1.1)

where xn is the average chain length, and p is the conversion rate of the monomers into polymers. This is an incredibly useful equation for predicting how long the reaction needs to proceed to obtain the correct molecular weight. As one can see, this defines an exponential relationship (Figure 1.1). As one might imagine, high molecular weights become increasingly more difficult to achieve for three reasons: (1) the frequency of reactive end groups meeting decreases; (2) the frequency of side reaction interference increases; and (3) when two or more monomer types are used in the reaction, it is difficult to ensure that the starting material concentrations are equal. This third point is an issue for users creating copolymer hydrogels, such as those consisting of monomer A and monomer B, where A-A does not react, nor B-B, but only A-B. To stop the reaction at a lower molecule weight, the user has a few options. One, the reaction can be rapidly cooled at the correct time point to slow down the polymerization rate as many step reactions have high activation energies. Two, a monofunctional material can be added to "cap" the end of the polymer, preventing it from further reactions. Lastly, if making a copolymer, a stoichiometric imbalance of the starting materials can be used. For example, if more A groups are used than B, eventually the polymer will have two A end groups on a chain and the B monomer will be completely consumed preventing further reactions with that polymer. The Carothers equation can be...

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