3D Bioprinting, Yet To Cross Many Bridges

3D Bioprinting, Yet To Cross Many Bridges

3D bioprinting is still under development and has many bridges to cross before entering the clinical world, particularly as an in situ direct application. Future developments are now concentrating on the combining of techniques to work in a complementary fashion to optimize the process of creating tissue-mimicking structures.

3d (3-dimensional) printing also called additive manufacturing (AM) has found applications in a variety of industries including construction, food, aerospace, and manufacturing. Recently, it has gained interest in medicine and tissue engineering applications as well. 3D bioprinting involves creating structures layer-by-layer by depositing a bioink, which is a mixture of cells, biocompatible polymers, and biomolecules. 3D bioprinting is a path to generate patient specific tissues and organs that when the patient needs a donor and in the times of donor scarcity, it can be a solution to resort.

Market dynamics

The 3D bioprinting market is projected to reach USD 1647 million by 2024 from USD 651 million in 2019, at a CAGR of 20.4 percent from 2019 to 2024, estimates MarketsandMarkets. Growing usage of 3D printing in cosmetic surgeries and innovations in the 3D bioprinting are expected to propel the market growth over the next 5 years. The technology is commonly used to print prosthetics and dental accessories, medical devices, and bone implants. The medical application segment is projected to expand at a significant pace, as the technology has the potential to reduce the drug development costs. Rising cases of chronic diseases and limited number of organ donors along with rising compliance in the drug discovery and development are also expected to boost market growth. Moreover, technological advancements, increased R&D investments, and growing geriatric population bases across the globe will drive the market further.

The research organizations and educational institutes segment accounted for the largest share of the market in 2019. Various research organizations across the globe are using 3D bioprinting intending to advance medical treatment. In line with this, academic and research institutes are collaborating with key market players for developing novel 3D bioprinted products. For instance, in 2019, Aspect Biosystems, Canada and the National Research Council of Canada collaborated to create a new 3D therapeutic model for the treatment of various central nervous system diseases, including Alzheimer’s disease.

The Asia Pacific market is estimated to grow at the highest CAGR, driven by the increasing research activities, growing demand for organ transplants, increasing number of initiatives by market players on expanding their presence in the APAC, and higher adoption of stem cell research. China and India are expected to offer significant growth opportunities for players in the market, owing to growing support from government bodies and an increasing number of conferences held in these countries.

The market is highly competitive in nature, with major players focused on creating awareness regarding the 3D bioprinting industry. Major players in the 3D bioprinting market host exhibition and seminars to display and promote the use of 3D bioprinters for diverse medical applications. The prominent players in the market have adopted various strategies for development, such as product innovation, product launches & approvals, and investment in R&D for advancements in 3D bioprinters, to sustain the competitive environment of the global 3D bioprinting market. Some of the companies in the global 3D bioprinting market include Organovo Holding, Inc., BioBots, Cyfuse Biomedical K.K., Luxexcel Group BV, TeVido BioDevices, LLC, 3Dynamics Systems Ltd., Aspect Biosystems, Stratasys Ltd., Materialise N.V., EnvisionTEC, Voxeljet AG, Oceanz, and Bio3D Technologies Pte. Ltd.

Challenges

Despite the successful studies and reported outstanding research efforts, the goal of 3D bioprinted organs has yet to be accomplished and there are several challenges which must be overcome.

Bioprinter technology. It needs to increase resolution and speed and should be compatible with a wide spectrum of biocompatible materials. Higher resolution will enable better interaction and control in the 3D microenvironment. Speeding up could build the opportunity to reach a commercially acceptable level and allow the process to be scaled up.

Bioink viscosity. Though there are a variety of methods to deposit cells in 3D bioprinting, the most popular techniques, and also those available commercially, are still inkjet and extrusion. Both types of printheads feature nozzles, and for that reason, the viscosity of cell-laden bioink must remain low. Cells are sensitive to mechanical stress, which can become significant when cell-laden bioinks are forced through a small orifice such as the printing nozzle. Thus, bioinks are usually shear-thinning, to ensure that cells can be deposited with high viability. This need for low viscosity during the deposition process is directly in contradiction with the printing of large constructs. To ensure that large structures are appropriately supported, each layer must maintain its shape when printed. However, this is almost impossible with low viscosity bioinks, as they quickly flow and spread after ejection from the nozzle. Currently, numerous materials and strategies are being explored to cover the conflicting needs of viscosity. A popular strategy is to use biocompatible polymers capable of crosslinking, and research efforts are focused on increasing the speed, reliability, and biocompatibility of the crosslinking step. The majority of the research in this area focuses on developing novel functional side groups for existing bioink polymers.

Choice of the cell source. The choice of cell source also determines the success of the printed construct. Stem cells have the ability to differentiate into multiple different cell types and can build different tissues. Hence, their differentiation and interaction with the scaffold material are essential.

Print speed. A hurdle to the fabrication of large 3D bioprinted constructs is the speed at which the tissue can be built. Due to the high resolution of 3D bioprinting, of which droplets can be as small as 20 µm in diameter, large constructs may require hours, if not days to complete. The problem here is in maintaining the cells in a physiological environment throughout the long printing process. This involves strict control over the temperature and humidity of the printed construct, as cells are fragile and sensitive to changes in their environment. Therefore, there is a need for both advancements in 3D bioprinters to support the construct, but also in increasing the printing speed.

Tissue vascularization. One of the hurdles is the need for vasculature in large tissues. Without vasculature to bring nutrients and oxygen to the center of large tissues, and similarly, to remove the waste, the size of the tissue is limited to the diffusion limit of oxygen, which is approximately 150 µm. There are several 3D bioprinting techniques to create artificial vasculature, such as using coaxial nozzles to create tubular structures with sacrificial cores, but it is the complex design of vasculature throughout organ that may prove difficult to replicate through 3D bioprinting.

Regulatory approval. One of the biggest challenges around 3DBP has been regulatory approval. The FDA normally regulates products and devices where the same design is used to treat many people. In the case of a biologic, one manufacturing batch can treat thousands to millions of people. The regulatory process assures that the product is safe and effective and that each of them are exactly alike. As with other precision medicines like T cell therapies, the major advantage of 3DP is that each product is tailored to the patient including using cells from the patient to create the tissue or organ. The downside, of course, is this poses a significant challenge for regulators because the cells are ideally suited to each individual patient but it also means that each treatment is unique. The FDA has been faced with the need to create new ways of regulating the process and not just the product. In the case of autologous T-cell therapies, recent approvals have opened the way for regulators to create guidelines for the manufacturing of bespoke and autologous tissues and organs. The FDA works closely with industry partners, including some leaders at GEHC, to create guidance for bespoke devices created using additive manufacturing, for printed biocompatible devices, and for living tissues and organs. This has provided a path to regulatory approval, though experts have not quite mastered it yet.

Way forward

Despite the successful studies and reported outstanding research efforts, the path to fully build a 3D bioprinted organ has yet to be accomplished and there are several challenges to be solved to further advance this exciting research theme. In addition to technical challenges, there are ethical problems involved in 3D bioprinting as in many other aspects of bioengineering. These are equality, safety, and human enhancement. Equality refers to whether the rich and the poor are going to have equal opportunities to access 3D bioprinting. Personalized medicine will be costly and how will the poor afford it? Is this technology then going to be available for only those can afford?

Safety is interested in if this new technology going to be safe for humans and whether the responsible personnel are going to be trained sufficiently to handle it? Lastly, are experts going to use this novel technology to build better humans? Replace some organs with a new one that supersedes the earlier? For example, are humans going to have a better muscle tissue that does not fatigue easily? These questions and technical concerns will need to be addressed down the road before this novel technology becomes fully operational and effective. 

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