Introduction
As of today, over 100,000 people are on the national transplant waiting list, and 17 people die each day waiting for an organ transplant (HRSA, 2023). For many patients, getting an organ transplant is an urgent matter, and tissues and organs from donors are simply not readily available. However, as technology advances, these body parts will become almost immediately accessible– and they won’t come from a body at all. Instead, they will be produced in labs through a method called bioprinting.
What is Bioprinting and How Does it Work?
As many already know, 3D printing is where a machine reads a digital 3D file and replicates it layer by layer using filament, which can be a variety of materials and is most often plastic. Bioprinting is just 3D printing but with biomaterials. Bioprinting machines follow a digital blueprint layer by layer to replicate living tissues inside our bodies. Eventually, scientists hope to reproduce fully functional organs through bioprinting and assembly. By achieving this, organ transplants will become cheaper, more accessible, and far less dangerous.
Before bioprinters begin the printing process, they are given a digital blueprint to read. These files are oftentimes created from CT and MRI scans. Next, a cartridge containing a mixture of the chosen cell type and bioink type must be loaded. Scientists will choose the cell type based on what tissue they intend to create and will then choose a bioink that allows the tissue to adopt desired structure and function (Cellink, 2023). In the context of a transplant, the cells and bioink chosen will be biologically compatible with the host (or taken from the host), reducing the likelihood of an autoimmune response (Saini, 2021). Bioink is a mixture of biomaterials that ensures that the tissues or organs printed have the correct functionality (Gungor-Ozkerim, 2018). Additionally, specific printing equipment is used for different types of structures. Crosslinking is a process that often follows printing in order to stabilize the tissue or structure. This is done by treating the construct with ionic solution or UV light (Cellink, 2023).
Origins
Bioprinting made its debut at Clemson University in the early 2000s. This is where Professor Thomas Boland and his group created the first bioprinter by modifying a commercial ink printer to print cells in a pattern. Since then, major advances have been made revolving around this very idea. Companies were created to specialize in producing affordable bioprinters. Similarly, there are also companies that focus on developing the bioinks used for these printers (Thayer, 2020).
4D Bioprinting
Recently, there has emerged a new type of bioprinting referred to as 4D bioprinting. It is 3D bioprinting with a new element incorporated: time. This method of bioprinting produces tissue that is able to transform its properties based on internal or external stimuli over time, similar to natural tissue. 4D bioprinting works because of “smart materials.” These materials sense changes in temperature, pH, magnetic field, moisture, light, and more. By sensing these changes, the materials are able to change shape. This allows for many functions including self-assembly, self-healing, and self-reproducing (Moqaddaseh, 2022).
Currently a developing field, 4D bioprinting will further optimize currently dangerous transplants by making them far less so. For example, autografting, transplanting from one part of an individual’s body to another, has a high risk of donor site morbidity that can be solved by the regenerative abilities of 4D bioprinted scaffolds (reproductions of native tissue combined with stem cells and other biomaterials) (Saini, 2021). Applications of 4D bioprinting could include substitution of invasive surgeries, tissue regeneration, drug delivery, bioactuation, biorobotics, and biosensing (Shukufe, 2021). 4D bioprinted organs will be able to provide patients with safer and more effective transplants even compared to 3D bioprinted organs.
Challenges
Currently, the most prevalent challenge in tissue engineering is the inability of modern bioprinting technology to replicate more complex and heterogeneous structures (Thayer, 2020). The prefix “hetero” means different, and structures in the human body are made up of different cells or tissues in complex patterns that allow them to function effectively. Mimicking this biological phenomenon is especially tough, but there is extensive research within this field producing new solutions. For example, a 2016 study conducted by Dr. Colosi and colleagues demonstrated the potential of a microfluidic technique of bioprinting to reproduce heterogeneous structures (Colosi, 2016).
What’s more, finding the correct materials also proves difficult especially for 4D bioprinting. Finding the appropriate biomaterial to perform a specific function is a challenging task, and ensuring that it is safe for patients limits the options that scientists have (Ramezani, 2023).
Controlling the degradation rate of these bioprinted materials is also challenging. The degradation rate of these structures must be compatible with the function that they are serving. There are potential solutions to this problem that scientists are exploring, such as creating new biomaterials and creating new combinations of materials (Ramezani, 2023).
Prospects
Needless to say, 3D bioprinting is on the road to save millions of lives in the near future. The development of bioprinted organs would allow organ and tissue transplantation to not only become more accessible for many people, but also personalized to alleviate rejection and other complications. The transformational properties of 4D bioprinting will optimize the effectiveness of the operation.
Furthermore, bioprinting can advance medicine in countless other ways. With 4D bioprinting technology, it will be far easier to conduct anything from highly invasive surgeries to treatment of viral infections (Yi, 2021). By producing printed organs, scientists will be able to use 3D cell culture to conduct clinical trials that will not cause harm to animals while yielding more accurate results (Thayer, 2020). With its instrumental applications, it is easy to see that bioprinting plays an important role in the future of biomedicine, and it is unmistakably the future of organ transplants.
References
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Colosi, C., Shin, S.R., Manoharan, V., Massa, S., Costantini, M., Barbetta, A., Dokmeci, M.R., Dentini, M. & Khademhosseini, A. (2016). Microfluidic bioprinting of heterogeneous 3D tissue constructs using low-viscosity bioink. Adv. Mater., 28(4), 677-684. https://doi.org/10.1002/adma.201503310
Gungor-Ozkerim, P. S., Inci, I., Zhang, Y. S., Khademhosseini, A., & Dokmeci, M. R. (2018). Bioinks for 3D bioprinting: an overview. Biomaterials science, 6(5), 915–946. https://doi.org/10.1039/c7bm00765e
Moqaddaseh A.N., Mohsen A., Ali Z., Mehrdad A.N., & Mahdi B. (2022). 4D printing: a cutting-edge platform for biomedical applications. Biomedical Materials, 17(6), 062001. https://doi.org/10.1088/1748-605X/ac8e42
Organ donation statistics. (2023). Retrieved from https://www.organdonor.gov/learn/organ-donation-statistics
Ramezani, M., & Mohd Ripin, Z. (2023). 4D Printing in Biomedical Engineering: Advancements, Challenges, and Future Directions. Journal of Functional Biomaterials, 14(7), 347. http://dx.doi.org/10.3390/jfb14070347
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