3D printing of functional biomaterials for tissue engineering
Graphical abstract
Introduction
Three-dimensional (3D) printing has led to significant advancements in many areas in the past two decades, including aerospace, consumer products, arts, food industry and manufacturing [1•]. With the recent advances of 3D printing technologies, a growing number of researchers in the biomedical engineering field are employing 3D printing as a transformative tool for biomedical applications, especially for tissue engineering and regenerative medicine. Tissue engineering is an emerging field that aims to develop biological substitutes of native human tissues or organs for in vitro drug screening to decrease the use of animals and increase the reliability of testing results, or for in vivo transplantation to mitigate the organ shortage and transplantation need. Recent research has greatly increased awareness of the dramatic differences in cell behavior between 2D and 3D culture systems. Culturing cells in 3D provides a more physiologically relevant environment to guide cell behaviors and enhance their functions [2, 3, 4, 5••]. Therefore, great efforts have been made to develop 3D biofabrication techniques that can generate complex, functional 3D architectures with appropriate biomaterials and cell types to mimic the native micro-environment and biological components.
In this review, we discuss the most dominant and important examples of 3D printing modalities and their applications in tissue engineering and relevant biomedical research. While cell source and biomaterial are two other key components in 3D biofabrication for tissue engineering, we will focus on the 3D biofabrication platforms and their end products to present the state-of-the-art 3D bioprinting capability. More discussion on the choice of cell types and biomaterials can be found in a recent review by Murphy and Atala [1•]. We first introduce the current prevailing 3D bioprinting techniques, including inkjet bioprinting, extrusion bioprinting and light-assisted bioprinting. Examples of the printed scaffolds are presented to demonstrate the printing capability as well as the limitations. Emphasis is put on the recently developed light-assisted bioprinting systems, including digital light processing (DLP)-based bioprinting and laser-based bioprinting, for their superior printing speed and resolution. Then we specifically discuss 3D printing of vascularized tissues, as this represents one of the most fundamental challenges in tissue engineering. Lastly, we summarize the challenges and future directions of 3D bioprinting for tissue engineering.
Section snippets
Overview
A majority of the traditional methods for creating 3D scaffolds — including electrospinning [6], freeze-drying [7], gas foaming [8, 9], particle or porogen leaching [10, 11] — have control only on the bulk properties of the scaffolds and do not allow precise control of the internal architecture and topology [12•]. Inspired by photolithography in electronics manufacturing, photomasks were used to dictate the polymerization of photosensitive biomaterials to create 3D cell-laden hydrogel scaffolds [13
Inkjet and extrusion based bioprinting
For the platforms to be biocompatible with cell work, printing systems and technologies that were used in non-biological applications have been modified to deal with biocompatible materials and to minimize any potential compromise on cell viability [16, 17]. The early development of the bioprinting systems to print cellular assemblies that mimic their respective architecture in organs originated from modifying commercially available inkjet printers [16]. Instead of dispensing ink, these inkjet
Light-assisted bioprinting
In addition to inkjet printing and extrusion-based printing technology, light-assisted bioprinting platforms are increasingly being used for cell printing and tissue engineering applications. These systems mostly involve the use of photo-polymerization of biomaterials and can print a variety of cell types with good cell viability [27, 28]. There are two sub groups of light-assisted bioprinting systems: DLP-based printers and laser-based printers.
As shown in Figure 2a, the DLP printer developed
3D printing of vascularized tissues
Creating functional vasculature represents one of the most fundamental challenges in tissue engineering. For large engineered tissue constructs, vascularization is pivotal for maintaining viability, especially in the case of highly metabolic cardiac tissue [44, 45]. Strategies to stimulate the vascularization of implanted tissue substitutes include chemical modification of biomaterials, optimization of pore sizes to facilitate blood vessel ingrowth, and incorporation of pro-angiogenic growth
Discussion
Although at its early developmental stage, 3D bioprinting is emerging as a promising tool in the tissue engineering field, providing bioengineering researchers with the unprecedented capability to engineer complex 3D biological architectures. Significant progress has been achieved in developing powerful biofabrication systems to meet various requirements of bioprinting intricate biomimetic structures with a variety of biomaterials and cells as discussed in the prior sections. However, there are
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
This project is supported in part by grants from the California Institute for Regenerative Medicine (Grant no. RT3-07899), the National Institutes of Health (Grant nos. EB017876, EB012597), Department of Defense (Grant no. W81XWH-14-1-0522), National Science Foundation (Grants nos. 1547005 and 1332681), and the National Natural Science Foundation of China (Grant no. 81422025).
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