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In virtue of today’s aging population, the growing need for tissue and organ transplants has driven the exploration of a seeming sci-fi phenomenon: regenerative medicine. Regenerative medicine refers to “the process of replacing, regenerating, or engineering human cells, tissues, or organs to restore or establish normal function [4]. Synthetic tissues usually communicate through a “collection of compartments” that are patterned in a 3D design, made of “materials designed to substitute for natural tissues and even exhibit enhanced properties” [3]. Similarly, artificial organs are defined as “engineered devices that can be implanted or integrated into a human body - interfacing with living tissue - to replace a natural organ, to duplicate, or to augment a specific function” [8]. Artificial organs can be classified into three sectors according to their building materials: (1) mechanical, made of materials such as plastics and metals, (2) biomechanical, made of both living cells and inanimate polymers such as plastic, and (3) biological, made of living cells, biodegradable polymers, and metal [8].
In order to understand how tissue engineering works, it is first necessary to understand the levels of organization of living things. Cells are the smallest unit of life. In biology, structure suits function, so cell types vary in appearance to suit specific functions. A group of the same cell type together makes tissues. A group of tissues that work to perform the same complex function is called an organ. Cells make up tissues, which make up organs, which make up organ systems. Thus, tissue engineering revolves heavily around reproducing specific cell types to create tissue.
Groups of cells are held together by a jelly-like structure called the extracellular matrix. Aside from holding cells together, the extracellular matrix works to relay signals and messages between cells and other nearby structures. These signals allow cells to “respond, interact with their environments and organize into tissues and organisms” [7]. Researchers have manipulated this signaling mechanism of the extracellular matrix to repair existing damaged tissues and create new ones [7].
At present, artificial tissue and organ engineering is not yet widely used for human treatment. Artificial skin and cartilage are two examples of FDA-approved engineered tissues [7]. Some additional engineered organs that have been implanted in humans include supplemental bladders, arteries, and trachea [7]. Tissue engineering for human use remains extremely costly. Thus, although human heart, lung, and liver tissue have been successfully engineered on occasion, these tissues are not likely to be used for human transplant in the near future because of the high cost, as well as the difficulty of fully reproducing these complex organs [7]. While not yet fully reproducible for human transplant, these tissues are extremely useful for clinical research of new drugs and treatments. The use of these artificial human tissues and organs in research reduces the need for pharmaceutical testing on animals. Further, tissue engineering also has the potential to improve the health outcomes of the most common age-associated transplants, such as knee and hip replacements. Tissue engineering of the knee joint cartilage could potentially reduce replacement: loosening, degradation with time, and inflammation [5].
Recently, there has been a lot of progress in tissue engineering with the advancement of 3D bioprinting. 3D bioprinting allows for the ability to “pattern and assemble cells and extracellular matrix in three-dimensions to create functional tissue constructs [2]. Further advancements in bioprinting are hoped to elicit further advancements in regenerative medicine. Complete 3D structures produced by 3D bio-printing have the potential to explain the issues with reproducing complex tissues and organs that have not yet been transplanted for human treatment.
The average time on the waitlist for the most transplanted organ - the kidney- is three to five years in the United States [1]. This waitlist is even longer in more populated states - at an average of 10-12 years for a kidney transplant in California [1]. Sadly, a US-based study found that nearly half of the candidates older than 60 and on the kidney transplant list are projected to die before they receive a transplant [6]. Thus, the enormous potential of tissue and organ regeneration in improving both morbidity and mortality rates amongst the ill and wounded cannot be overstated.
References
1. American Kidney Fund. (2022, March 28). Transplant waiting list. American Kidney Fund. Retrieved June 13, 2022, from https://www.kidneyfund.org/kidney-donation-and-transplant/transplant-waiting-list
2. Arslan-Yildiz, A., Assal, R. E., Chen, P., Guven, S., Inci, F., & Demirci, U. (2016). Towards artificial tissue models: Past, present, and future of 3D bioprinting. Biofabrication, 8(1), 014103. https://doi.org/10.1088/1758-5090/8/1/014103
3. Bayley, H., Cazimoglu, I., Hoskin, C. (2019). Synthetic tissues. Emerg Top Life Sci. 3 (5): 615–622. doi: https://doi.org/10.1042/ETLS20190120
4. Manivasagam, G., Reddy, A., Sen, D., Nayak, S., Mathew, M. T., & Rajamanikam, A. (2019). Dentistry: Restorative and regenerative approaches. Encyclopedia of Biomedical Engineering, 332–347. https://doi.org/10.1016/b978-0-12-801238-3.11017-7
5. Minuth, W. W., Sittinger, M., & Kloth, S. (1997). Tissue engineering: Generation of differentiated artificial tissues for biomedical applications. Cell and Tissue Research, 291(1), 1–11. https://doi.org/10.1007/s004410050974
6. Schold, J., Srinivas, T. R., Sehgal, A. R., & Meier-Kriesche, H.-U. (2009). Half of kidney transplant candidates who are older than 60 years now placed on the waiting list will die before receiving a deceased-donor transplant. Clinical Journal of the American Society of Nephrology, 4(7), 1239–1245. https://doi.org/10.2215/cjn.01280209
7. U.S. Department of Health and Human Services. (2022). Tissue engineering and regenerative medicine. National Institute of Biomedical Imaging and Bioengineering. Retrieved June 13, 2022, from https://www.nibib.nih.gov/science-education/science-topics/tissue-engineering-and-regenerative-medicine
8. Wang, X. (2019). Bioartificial Organ Manufacturing Technologies. Cell transplantation, 28(1), 5–17. https://doi.org/10.1177/0963689718809918
Contributors
Author: Aseelah Saiyed
Editor: Kayjah Taylor
Health Scientist: Aseelah Saiyed
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