**1. Introduction**

Tissue engineering is a newly developing field of a combination of biology, materials method and engineering to develop functional substitutes for damaged tissues [1]. According to the broad range of application on cell types, it can be divided into skin, bone, vascular, kidney, and liver tissue engineering. After years of powerful progress, a set of novel tissue culture [2], replacement [3] and implantation technologies have been developed, allowing fabricating artificial extracellular matrices, namely scaffolds, to bear stem cells, growth factors, or other biological nutrients aiming at repair of tissue function. Scaffolds are bulk bioactive materials with specific porosity and structure to contribute to the formation new tissues for completing the medical task. In 2009, first artificial tissue was implanted successfully into a patient who suffered from the tracheoesophageal defect [4]. This case confirmed that artificial organs stand

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

a chance to substitute the insufficient supply of standard organ in transplantation, which can drastically decrease the demand for living tissue. Now challenges for tissue engineering are the requirements for certain special structures, mechanical property, biocompatibility, and vascularization of tissues for implantation. In efforts to address these issues, it is important to employ an advanced manufacturing technology, which is flexible enough to build the threedimensional (3D) structure with complex inside feature.

**2. Key considerations for tissue engineering**

**2.1. Components consideration for tissue engineering**

cussed in the following sections.

applied for tissue engineering.

performance [19].

To extend the application of 3D printing into the area of tissue engineering, it is a prerequisite to have detailed knowledge of the biomaterial that is suitable for tissue engineering and can be processed by 3D printing meanwhile. The key questions to be considered for tissue engineering are components selection and mechanical features of the scaffold, which are dis-

3D Printing of Scaffolds for Tissue Engineering http://dx.doi.org/10.5772/intechopen.78145 139

The choice of materials for tissue engineering makes up a significant portion of influence on the performance of scaffolds. Not only do the material properties should be considered, but the cellular or tissue response from the specific position should be optimizing. For all of these selected materials, nontoxicity is just the basic requirement for printing materials. In order to facilitate the cell proliferation while considering the printability from an engineering perspective, a wide range of factors should be taken into consideration when selecting printing materials for a scaffold, such as biocompatibility, bioactivity, biodegradability, and non-immunogenicity. A myriad of biomaterials suitable for scaffolds has been developed, including polymers, ceramics, metals, and even more are created each year. A range of are

Polymer materials have a long history in the medical industry [13]. Over last 40 years, a variety of biodegradable polymers have been developed, including synthetic and natural polymer materials. The benefits that synthetic polymers prevail over natural are that synthetic polymers can tune their initial mechanical properties and they have an abundant source of raw materials. Saturated aliphatic polyesters, such as poly (lactic acid) (PLA), polycaprolactone (PCL), poly (glycolic acid) (PGA), or their copolymers, are most frequently used tissue materials, as well as can be used as 3D printing materials [14–16]. Moreover, polymeric composites that doped with reinforcement materials, such as bioactive ceramics or carbon fibers, are allowed to be processed by 3D printing [17, 18]. The incorporation of bioactive hard phase into polymers not only enhances the mechanical property of scaffolds but also the biological

Ceramics and bioactive glasses have been widely investigated for replacement and repair of hard tissues, such as bone tissue and teeth [20]. Traditional non-degradable bio-ceramics, such as alumina and zirconia, have high hardness and resistance to wear, making those excellent candidates in the area of joint replacement. However, their biological inertness limits the success of tissue engineering, more or less. Therefore, further efforts made by researchers were to find a ceramic with both high mechanical property and bioactivity. It is found that synthesized hydroxyapatite has close chemical components to the inorganic phase in human bone [21]. When implanted into human body, the development of the interface between HA and host tissue involves complex interactions. Solubilization of HA provides adequate beneficial ions for forming collagen and new bone tissue. Another material family used for

Reform in materials processing methods arose from the pressing needs for high-performance and multi-functional materials for broad applications in energy storage, transportation, lightweight structures, and biomedical engineering, among which 3D printing are in the highest interest by the community of material science research [5–8]. In conventional processing methods, waste is cutting off from the raw material by milling, planning or grinding, and thus desired structure is obtained by these subtractive methods [9]. On the contrary, 3D printing is known as an additive manufacturing method, building the required structure layer by layer, or even pixel by pixel. The terminology "3D printing" firstly emerged was used to refer the work done at MIT in 1993, modifying a standard inkjet printer to a custom processing equipment [10]. Over last thirty years, a variety of innovative 3D printing technologies have been developed, which can be categorized into three groups including powder-based 3D printing, ink-based 3D printing, and polymerization-based printing. In all these cases, the printed structure is firstly modeled using a computer-aided design software packages, such as UG, CATIA, ProE, or other customized software. Then a ST-format file contained all the model information is exported to the 3D printing system to control the moving track of printing device and constructing the structure layer by layer.

Early use of 3D printing focused on its raid manufacture process, which is suitable for pilot production in lab or factory. Now, 3D printing is one of the most flexible technique enables direct manufacturing complex shape with high resolution, as well as processing highly customized medical products combined with image reconstitution technique. The advancement of 3D printing technologies has provided researchers and doctor's abundant tools to promote the functional scaffolds, which meet the strict criterion of tissue engineering. In addition, broadening choices in materials that can be processed by 3D printing offers researchers "recipe" to tune the biology performance of scaffolds. The ideal role of 3D printing in tissue engineering is to provide the suitable microenvironment for cells to induce cell proliferation and differentiation toward the functional tissue. There are two main modes of 3D printing using for tissue engineering currently. One is creating 3D cell-laden scaffolds that the cells are contained within the bioink. Another is fabricating molds or scaffolds, which can be cultured with cells in-vitro after fabrication [11, 12].

The main objective of this chapter is to provide a comprehensive review of the advanced 3D printing methods for tissue engineering. This chapter is structured as follows: Section 2 describes the basic need for tissue engineering. Then, a variety of advanced 3D printing methods for tissue engineering are introduced in Section 3. Finally, current issues for 3D printing methods applied in tissue engineering and potential investigations in the future are discussed.
