**Abstract**

Tissue engineering techniques enable the fabrication of tissue substitutes integrating cells, biomaterials, and bioactive compounds to replace or repair damaged or diseased tissues. Despite the early success, current technology is unable to fabricate reproducible tissue-engineered constructs with the structural and functional similarity of the native tissue. The recent development of 3D printing technology empowers the opportunities of developing biofunctional complex tissue substitutes via layer-by-layer fabrication of cell(s), biomaterial(s), and bioactive compound(s) in precision. In this chapter, the current development of fabricating tissue-engineered constructs using 3D bioprinting technology for potential biomedical applications such as tissue replacement therapy, personalized therapy, and in vitro 3D modeling for drug discovery will be discussed. The current challenges, limitations, and role of stakeholders to grasp the future success also will be highlighted.

**Keywords:** 3D printing, scaffold, drug delivery, regenerative medicine, tissue engineering

#### **1. Introduction**

3D printing is a process whereby a real object is created starting with a virtual 3D digital model. It was first developed in 1986 by Hull and Lewis which is an improved stereolithography system using photochemical processes in which light causes chemical monomers to link together to form polymers and generate a solid object [1]. This technology is capable to fabricate a super complex geometry or features by accurately follow the computer-aided design (CAD) model. The fabrication requires appropriate materials that gradually released and overlapped in layerby-layer fashion by 3D printer. The type of material chosen is crucial to ensure the printed object that can be used for further settings and applications. Various types of metals, polymers, ceramics, and composites such as polycaprolactone (PCL), polyethylene glycol (PEG), polylactic acid (PLA), acrylonitrile butadiene styrene (ABS) plastic, stainless steel, titanium, calcium phosphate, and silica can be used as starting materials in 3D printing [2–4].

Generally, there are four main applications of 3D printing in the medical field, which are as follows: (a) drug delivery, (b) surgical devices/implants, (c) operative planning, and (d) tissue engineering [5–12]. The 3D printing application for drug delivery is extensively used in the pharmaceutical industry to develop sustained release medication [5]. Modulation of the shell thickness as well as the shape of the 3D printed capsule allows precise control of the drug release rate [13]. 3D printing enables a fast and cost-effective way of fabricating personalized medical implants. The capability of producing custom implants gets rid of the need for adjustments during surgery that saves time as well as reduces the cost of operation and the risk of medical complications. This is particularly beneficial where metal implant interfaces with living bone and tissue. The electron-beam melting (EBM) and direct metal laser sintering (DMLS) technologies are both now used in the production of standard and customized implants. Surgical tools are generally designed to work with many patients. However, by fabricating patient-specific tools, it would decrease the risk of complications during surgery [13, 14]. Patient anatomy will be imaged using imager and transferred into the 3D design in CAD to create suitable tools that can be easily controlled during operation. In operative planning, the 3D printing also would provide surgeons with a visualization of the complex injuries. They can plan and strategize their work and choose specific tools required. Some of the common applications that require a 3D model are complex pelvic trauma [15], pediatric deformities [16], and osteotomies [17]. Furthermore, advances in 3D printing technology enable the possibilities of constructing living human tissues in the lab hoping to demonstrate structural and functional similarities as native tissue in the human body [12]. The biggest challenge is to construct thick tissue and to ensure the diffusion of oxygen and nutrients for cellular viability [14].
