Bioprinting is a technology of combining cells, biomaterials and other supporting molecules into functional tissues [1]. Due to the large demand for organ transplantation and limited organ donors, bioprinting might be an innovative method to solve the organ shortage [2]. At the same time, it has the advantages of accurate placement of the cells [3] and the ability to build complex internal structures [4] over other traditional tissue engineering methods. In addition, Bioprinting could also be implemented in drug testing and disease modelling [5]. In this essay, the achievements made in bioprinting will be first reviewed. After that, its prospects in clinical applications and current limitations will be discussed.
Since the first international meeting on bioprinting held in 2004 [8] and first patent registered in 2006 [7], bioprinting has experienced the development from printing the 2D tissues like skin, 3D tissues like heart valves and blood vessels to the ambitious goal of printing the whole human organ [1]. Currently, three main bioprinting technologies have been developed, which are extrusion bioprinting, inkjet bioprinting and laser-based bioprinting [1, 4]. Extrusion bioprinting is the simplest method and mostly used. It utilises piston or screw to extrude the bioink out of the nozzle continuously and build the tissue structure upon the substrate plate. However, there is a balance between the nozzle size and printing quality. Narrow nozzle means high resolution, but it has the disadvantages of long printing time and low cell viability due to high pressure on the bioinks. Increasing the nozzle size can prevent the drawbacks, but it will lead to a poor resolution [1]. Inkjet bioprinting uses liquids containing biomaterials and prints them like regular 3D printers. It possesses the advantage of high resolution and high printing speed, but it faces the problem of nozzle clogging when printing high viscosity bioinks [1]. Laser-based bioprinting is similar to laser writing. A transparent ribbon coated with energy absorbing layer and biomaterial layer should first be made. Then, a laser beam is utilised to heat the target position on the ribbon to create a region of high temperature and pressure. Thus, the biomaterial at the heating location will become a droplet and be propelled to the collection plate under it. It has the advantages of high resolution even accurate to a single cell. The non-contact during the whole process also leads to a high cell viability. However, this method can only print thin structures like cardiac and skin. Its high cost also obstacles it to clinical use [4]. Obviously, every bioprinting method has its pros and cons, thus selecting the proper method for specific purpose seems very significant. Additionally, the hybrid approach combining the advantages from different methods might be a promising direction in the future research [4].
Implementing these bioprinting technologies, several tissues have been successfully printed at human scale with good functionality [1, 3, 4]. These breakthroughs indicate a new way to overcome the limitations and challenges in traditional regenerative medicine. For example, a heart valve conduit with high viability and a considerable chance of clinical applications has been printed by [8] in 2014. This valve can prevent the drawbacks of a mechanical prosthetic heart valve like long-term wear and its thrombogenicity [3]. However, the printed valve still could not achieve the required mechanical properties at this stage [8]. Other tissues such as cardiac tissues, blood vessels, lymphatic vessels, tendons and sections of bones have also been printed and tested [4]. The noticeable progress shown in these areas indicates the great potential of bioprinting in future regenerative medicine.
In addition to its application in tissues regeneration and transplantation, bioprinting could also be applied in drug discovery and development [3, 4]. Potentially, bioprinting technology could create a large amount of testing materials to evaluate the toxicity and efficacy of potential drugs and cellular response to it before the clinical stage. It is obvious that more testing at the preclinical stage could reduce the attrition rate and development time during the clinical development process, which contributes to the majority of the cost [5]. Additionally, this suggests bioprinting might be a tool in developing personalised medicine, for the drug testing on individualised tissues could minimise the toxicity to specific patients and find the optimal treatment plan [4, 5]. Furthermore, bioprinting could also be used in disease modelling [9]. 3D tumor model developed by bioprinting has the advantage of modelling more detailed microvascular structures than traditional cancer modelling, so it could be a more useful tool for studying the tumor mechanism and metabolism [4, 10]. Thus, the application of bioprinting might pioneer medicine in several aspects and benefit countless patients in the near future.
Although various bioprinting technologies have been developed and applied, there are still several challenges and limitations waiting to be addressed. Firstly, bioprinting of whole functional organs still remains a challenge, due to their size and complexity [3, 4]. For example, the thickness of cardiac tissue causes difficulties in merging vascular systems into it and letting every cell at different depth respond to the electrical impulses properly [11]. For some specific organs like brain, the bioprinting of its neural tissue is still a challenge [4]. Secondly, there is a limitation of available bioprinting materials, for most materials used in traditional 3D printing lack biocompatibility and enough mechanical strength [3, 6]. There are two ways to deal with this challenge. The first one is to develop new bio-polymers [9] and the second one is to use stem cells [11]. However, the new biomaterials usually cannot be printed using traditional 3D printers, especially when they are lacking the structural integrity [3, 9]. Therefore, there is a need to build the new 3D bio-printing systems suitable for printing these new biomaterials [12]. Moreover, the resolution is another limitation of bioprinting due to the size of printing droplet or nozzle. The highest resolution of current bioprinter is about 20 micrometres, which is reached by laser-based bioprinting [9]. At the same time, inkjet and extrusion bioprinting can only reach about 50 micrometres and 100 micrometres [4]. However, capillaries in human tissues can be just 3 micrometres in diameter [9]. This also indicates the current bioprinting tissues cannot mimic the microvascular system perfectly inside the tissues. In addition, the slow printing speed is another factor limits the implementation and this problem must be solved to push forward bioprinting to clinical use [3, 9].
In conclusion, great progress has been made in bioprinting and huge potential in this field has been shown. By this method, various types of cells and biomaterials can be printed precisely at the pre-specified locations and formed complex tissues at human scale. These bioprinting tissues could be used as substitutes for diseased tissues, in drug discovery and other medical research like tumor modelling. However, there is still a long way from the ultimate goal of organ printing. The challenges of limited available biomaterials, vascularization and innervation inside the tissues, low printing resolution and long printing time still need to be overcome. Therefore, in order to achieve the goal of implementing bioprinting in regenerative medicine, efforts are necessary not only in bioprinting, but also in related subjects like material science, mechanical engineering and manufacture.