Date: December 5, 2022.
According to the HRSA, 105,800 patients are on the national transplant waiting list, while 17 people die each day waiting. Also, every 10 minutes another person is added to the transplant waiting list.
Let’s take a closer look at organ transplantation. While it is an incredible fact that one donor can save 8 lives and enhance the lives of 75 more patients, it is however, a very challenging and difficult procedure and is usually considered the last resort.
Initially, the foremost challenge is finding someone with a compatible blood type, similar body size, or similar biomarkers on their cells called human leucocyte antigens.
While a potential match is found, the transplant itself is extremely time-sensitive. When an organ is withdrawn from its blood supply, the tissue dies pretty quickly. This is because the cells switch to anaerobic processes, which cause an excess of metabolic waste production, increase in acidity, and ultimately cell death. When kept cold, organ death can occur in 4–6 hours for the heart or lungs and a day and a half for the kidneys.
Since the very beginning of transplantation, the major problem that surgeons have had to deal with has been organ rejection. In spite of initial acceptance, subsequent failure poses another threat known as AMR (antibody-mediated rejection), since our immune system perceives the transplanted organs as a large clump of foreign material and attacks them. To prevent these rejections, doctors prescribe immunosuppressants which inhibit the effects of calcineurin, a protein that aids in T-cell activation (a key event in the adaptive immune response). Other medications like corticosteroids are also available to treat inflammation. These medications, however, increase a patient’s susceptibility to illness, making even common infections deadly. Several studies claim that immunosuppressant-related issues account for over 20% of late kidney transplant failures.
Additionally, because the immune system reacts so strongly to some organs, such as the intestines, transplanting them can be quite challenging.
That’s a lot of jargon! Big shoutout to the scientists who overcame these challenges and introduced… Tissue Engineering!
Tissue engineering requires three things — engineering cells (the cells that make up tissues/ organs in the body), scaffolds (the architectural frameworks/ molds in which cells are seeded to make tissues/ organs) and biological factors (the engineering materials like growth factors).
What are engineering cells?
These are stem cells, the type of cells that have the ability to develop into other types of cells and make up tissues and organs in your body. Scientists can now create pluripotent embryonic stem cells that have the ability to divide and differentiate into any tissue/organ. This is done by genetically modifying adult stem cells obtained from blood, bone marrow and other resources. These engineered cells are known as iPSCs (induced pluripotent stem cells). Thank you Dr Shinya Yamanaka.
Next, What are scaffolds?
Scaffolds are basically molds in which engineered cells are seeded. As an example, if you want to make a trachea, scientists will take the trachea of a deceased person, flush it with powerful detergents, and decellularize it. All that’s left behind is the extracellular matrix, a meshwork of fibrous proteins and other molecules around which cells grow. Decellularization and seeding work well for simple organs and transport tubes. However, with complex structures it becomes difficult to seed the engineered cells in the right place within the scaffold. As a solution to this problem, scientists are currently using bioprinted scaffolds.
Inside the process of bioprinting.
Bioprinting uses biomaterials (engineered cells + growth factors) to create scaffolds in a layer-by-layer manner. Bioinks, a mix of living cells and compatible bases, such as collagen, gelatin, hyaluron, silk, alginate or nanocellulose, are used instead of inks and filaments. Cells are protected, nourished, and held together by a compatible base, also known as hydrogel. Overtime, these hydrogels slowly degrade and are replaced by the extracellular matrix, secreted by the cells.
In summary, researchers obtain stem cells, modify them, make bioinks with suitable growth factors, design tissues/ organs using computer software, click the print button and bam! The tissue or organ you want is printed!
But since any organ would die unless it was connected to a blood supply, researchers have been finding techniques to develop tiny blood vessels that can reach every crevice of a large organ. And guess what… They have been successful! (yay!)
The concept of bioprinting organs holds a promising future in solving the critical global issue of organ shortage. This has prompted regulatory authorities to create laws and guidelines to ensure regulatory compliance and counter the corresponding ethical issues.
Let me now shed some light on the next big thing, Bioprinted Organoids.
Organoids are stem cell-derived, self-organizing, 3-D miniature organs that imitate the architectural and functional complexity of native organs. They can revolutionize disease research in a profound manner. With its help, we can now clearly observe the most puzzling aspects of our own biology. The importance of this becomes even more apparent when studying complex human characteristics or diseases. For instance, bioprinted brain organoids can be used for drug target screening in neurological diseases. Researchers can now use bioprinting to efficiently and reproducibly prepare brain tissues for screening of potential drug targets for the treatment of Alzheimer’s disease, thereby avoiding animal experiments.
In the last few years, 3D systems have gained a lot of interest in the scientific community, especially when it comes to cancer research due to their realistic biochemical (body’s chemical composition) and biomechanical properties (body’s internal mechanism) . Scientists can now make tumor organoid models which provide a new approach for personalized cancer treatment. In addition to simulating tumor characteristics and tumor cell heterogeneity, it also captures human changes better than traditional animal models. We can now better understand disease pathophysiology (study of abnormal changes associated with disease) using 3D tumor microenvironments that effectively replicate signaling pathways and cellular functions.
In 2020, researchers at the University of Minnesota 3D printed a centimeter-sized heart organoid. This is a significant progress in organoid studies of the heart. Having the ability to bioprint stem cells in a manner similar to tissues and harnessing the ability to turn them into cardiomyocytes (heart cells), is genuinely fascinating! However, further exploration is required, since it showed promising results in small kinetic models, but the data is insufficient for large animals with thicker myocardial walls (heart muscle walls).
To sum it up, organoid bioprinting technology has the potential to revolutionize the paramount fields of developmental biology, disease pathology, cell biology, regenerative mechanisms, precision medicine, and drug screening.
Overall 3D printing is basically our childhood fantasy turned into reality… remember that show called Shaka Laka Boom Boom? Anything that the boy draws with his magic pencil turns into reality! Well, the same thing is happening around the world right now. Thanks to the very intriguing 3D printing technology!
If you had a 3D printer, what would you print first?
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