3D Bioprinting

Fundamentals, Principles and Applications

Ibrahim Tarik Ozbolat

• Publisher: Academic Press
• Year: 2016
• ISBN:
  9780128030301
• Topic: Medicina
• Subtopic: Tecnologia e forniture mediche

3D Bioprinting: Fundamentals, Principles and Applications provides the latest information on the fundamentals, principles, physics, and applications of 3D bioprinting. It contains descriptions of the various bioprinting processes and technologies used in additive biomanufacturing of tissue constructs, tissues, and organs using living cells. The increasing availability and decreasing costs of 3D printing technologies are driving its use to meet medical needs, and this book provides an overview of these technologies and their integration. Each chapter discusses current limitations on the relevant technology, giving future perspectives.

Professor Ozbolat has pulled together expertise from the fields of bioprinting, tissue engineering, tissue fabrication, and 3D printing in his inclusive table of contents. Topics covered include raw materials, processes, machine technology, products, applications, and limitations. The information in this book will help bioengineers, tissue and manufacturing engineers, and medical doctors understand the features of each bioprinting process, as well as bioink and bioprinter types. In addition, the book presents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics.

• Describes all aspects of the bioprinting process, from bioink processing through design for bioprinting, bioprinting techniques, bioprinter technologies, organ printing, applications, and future trends
• Provides a detailed description of each bioprinting technique with an in-depth understanding of its process modeling, underlying physics and characteristics, suitable bioink and cell types printed, and major accomplishments achieved thus far
• Explains organ printing technology in detail with a step-by-step roadmap for the 3D bioprinting of organs from isolating stem cells to the post-transplantation of organs
• Presents tactics that can be used to select the appropriate process for a given application, such as tissue engineering and regenerative medicine, transplantation, clinics, or pharmaceutics

1

Introduction

Abstract

This chapter introduces three-dimensional (3D) bioprinting technology starting by presenting a high-level perspective of tissue engineering and the game-changing role of 3D printing in tissue engineering through additive manufacturing of anatomically correct tissue scaffolds. It then introduces bioprinting or direct cell printing as an emerging technology that has great potential in creating de novo organs. There is a discussion of the components of bioprinting, including the hardware and software aspects as well as the bioink. The chapter then explains the history and evolution of bioprinting technologies, highlighting remarkable milestones during the last decade. Finally, bioprinting technologies are classified into three major groups including extrusion-, droplet- and laser-based bioprinting techniques.

Keywords

3D bioprinting; 3D printing; Classification of bioprinting techniques; Evolution of bioprinting; Tissue engineering

All truths are easy to understand once they are discovered; the point is to discover them

Galileo Galilei

Chapter Outline

1.1 Tissue Engineering

1.2 Three-Dimensional Printing in Tissue Engineering

1.3 Three-Dimensional Bioprinting

1.3.1 Principles of Three-Dimensional Bioprinting and Its Components

1.3.2 Historical Evolution

1.3.3 Classification of Bioprinting Techniques

1.4 The Organization of the Book

1.5 Summary

References

1.1. Tissue Engineering

Since the first successful kidney transplant in 1954 was performed between two identical twins (Merrill et al., 1956), organ transplantation has become a life-saving procedure for many disease conditions that hitherto were considered incurable. In the United States of America (USA), an average of 79 people receive transplants every day; however, the number of donors is much less than the number of patients waiting for a transplant (Ozbolat and Chen, 2013). Moreover, infections and rejection of the tissue by the host often make the transplantation process more challenging (Desmet et al., 2008). The solution to this problem, as with the solutions to other grand engineering challenges, requires long-term solutions by building or manufacturing healthy living organs from a person’s own cells, which would relieve suffering and save lives.

Current medical procedures aim to restore tissue function to patients with diseased or damaged tissues through tissue transplantation and implants. Tissue engineering has grown as a multidisciplinary scientific field of biology, biomaterials, and engineering that has rapidly emerged and combines engineering principles with life sciences to replace damaged tissues or restore malfunctioning organs by mimicking native tissue (Langer and Vacanti, 1993). One of the common strategies in tissue engineering is to develop engineered scaffolds that provide an optimum environment or housing for cell attachment and growth, tissue regeneration, fluid movement, and structural integrity. The main reason for the scaffolding approach is the need to maintain the shape and mechanical properties of the mimicked tissue engineered, to assist in cell attachment, and to provide a substrate for cell proliferation into three-dimensional (3D) functioning tissues (Hutmacher et al., 2004). Developed 3D porous engineered constructs enable cell attachment, proliferation, and regeneration. Upon implantation, scaffold material starts degrading, and cells grow and proliferate through pores. Eventually, degraded sites constitute new tissue and restore the functionality of the diseased or damaged tissue.

Several traditional fabrication techniques have been used for tissue scaffolds, including phase separation, membrane lamination, melt molding, fiber bonding, molding, gas foaming, solvent casting, freeze drying, and particulate leaching (Leong et al., 2003). Most of the abovementioned techniques are, however, limited in terms of manufacturing reproducibility and flexibility. Building patient-specific anatomically correct shapes with well-controlled internal geometry, including pore size and pore distribution, is highly challenging. In addition, they include manual interventions and inconsistent and inflexible processing procedures with the use of toxic solvents and porogens that limits the inclusion of cell and protein impregnation. 3D printing, also known as additive manufacturing, has been a game-changing technology in the rapid manufacturing of complex products and has been adopted in tissue engineering for biofabrication of 3D scaffolds (Hamid et al., 2011).

1.2. Three-Dimensional Printing in Tissue Engineering

3D printing opens a revolutionary era in medical product design and development and is widely used to fabricate 3D scaffolds by layer-by-layer deposition. In general, biomaterials are deposited through a dispensing unit to specific points on the space to create a scaffold with well-controlled geometry. Three-dimensional bioprinting has been extensively used for building tissue-engineered constructs due its repeatability and high accuracy in microscale fabrication resolution (Sachlos et al., 2003). 3D printing techniques such as fused deposition modeling, precision-extrusion deposition, selective laser sintering, three-dimensional printing, and stereolithography (SLA) have been used to fabricate biologically active tissue constructs by replacing the materials being processed with biocompatible materials such as synthetic and natural polymers, natural and inorganic ceramic materials, or recently developed biodegradable metals (Ozbolat and Hospodiuk, 2016). Adaptation of 3D printing into tissue engineering brings unique capabilities in rapid fabrication of tissue scaffolds with controlled porosity and internal architecture, tunable mechanical and structural properties, and the ability to load drug or protein molecules for enhanced cellular response and customized/multifunctional characteristics, which can guide the cellular environment for enhanced tissue regeneration. To achieve a truly interconnected internal architecture for cell growth and proliferation, an internal structure is formed by depositing cylindrical microfilaments parallel to each other in every layer using a certain lay-down pattern.

Despite its great benefits in the biofabrication of anatomically correct tissue scaffolds, 3D printing in tissue engineering faces several limitations in the generation of complex tissues and organs for transplantation or other uses. First of all, there is a lack of precision in cell placement due to manually driven seeding and placement of cells on the scaffold microarchitecture. It is highly challenging to manually seed, place, and pattern cells precisely in a scaffold construct; however, several cell type groups are organized and interact in very complex patterns in natural tissues and organs. In addition, seeding cells in high cell density is very limited because cells can only attach on the surface of the scaffold and cannot penetrate into the biomaterial in the scaffold. Scaffold biomaterials also occupy a significant volume of space in the scaffold, which do not let the cells grow into sufficient cell numbers. In addition, the need for a vascular network is essential to develop thick tissues and organs to facilitate an efficient exchange of media to keep the cells oxygenized, viable and functional, and it is very difficult to create such a network using 3D printing technologies alone. These difficulties have led many researchers toward the development of bioprinting technologies, where cells can be encapsulated in high cell density and printed and patterned into desired spaces to obtain anatomically correct tissue constructs with patterned cells interacting as in native tissue and organs.

1.3. Three-Dimensional Bioprinting

Three-dimensional bioprinting is an emerging field that makes a revolutionary impact on medical sciences. It has gained significant attention from numerous researchers from various academic disciplines as well a...