Organ transplants are crucial in saving over 100,000 patients every year, but unfortunately only around 36,000 patients actually receive one (Rajab et al., 2020). There have been many attempts to create artificial organ transplantation methods, but there are many reasons that they are not accessible to enough people. The cost of treatments such as dialysis make them inaccessible to people in lower-income neighborhoods who need these treatments to survive (Rajab et al., 2020). There is a lack of viable organs for transplantation because they must fit many requirements in order to ensure compatibility with the patient’s body. Some people are also deemed ineligible for an organ transplant but are still in need of an alternate treatment option in order to survive. 

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Scientists have thus discovered the need for artificial organ transplants in order to create more accessible and potentially safer alternatives to donor organs. They have begun using the process of tissue decellularization, which is used to isolate the extracellular matrix (ECM) from an organ or tissue by removing its cells (Rajab et al., 2020). This isolation process leaves behind the empty ECM scaffold that can be used with patient-derived cells for transplantation (Rajab et al., 2020). This method of tissue engineering should be more widely accessible than traditional organ transplants because it can be curated to the patient, so they no longer will have to wait for a donor organ to perfectly match their body (Rajab et al., 2020). Implantation of the engineered tissue would also allow for a smoother integration process because, since the cells originated from the patient, there would be no need for immunosuppressive medication (Rajab et al., 2020). Cells from a donor’s body are no longer needed, making the process much safer with a significantly lower risk of rejection of external cells by the patient’s immune system.

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In order to understand how decellularized tissue engineering works, it is important to understand the role of the ECM in the body. It is a large network of proteins and molecules that provide structure and support to cells and tissues, allowing cells to interact with each other and regulating enzyme activity and cell survival (NCI, n.d.). This structure is extremely helpful for tissue engineering because it can be used as scaffolding with the patient’s own cells in order to create an alternative form of organ transplantation (Rajab et al., 2020). 

Development of decellularization and ECM production was first recorded in 1979. This brought the beginning of creation of ECM for simple tissues, including skin, vascular tissue, heart valves, and bladder in the early 2000s (Rajab et al., 2020). Many of these innovations have only been tested on animals so far, but some have been proven to work well in humans (Rajab et al., 2020). Some of the first successful implantations in humans have included modeling the great saphenous vein and liver grafting (Rajab et al., 2020).

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There are also multiple ways for scientists to decellularize the tissue to strip the ECM scaffold of the cells, with two main types of processes: chemical and physical (Rajab et al., 2020). Freeze-thawing is a physical decellularization process that ruptures cells through a process of freezing and rewarming without using too many chemicals in order to reduce the level of toxicity of the transplant (Yang et al, 2021). Another type of physical decellularization is a process by which mechanical tools are used to rupture cell membranes through physical force (Rajab et al., 2020). Unfortunately, both of these types of decellularization tend to cause significant damage and disruption to the ECM, so they are not suitable options for fragile tissues and organs such as the lungs (Rajab et al., 2020). 

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Another type of tissue decellularization is chemical, which comes in three forms of detergent: ionic, nonionic, and zwitterionic (Rajab et al., 2020). The nonionic detergents disrupt lipid interactions but spare those between proteins, which means that they have preferential disruption of cell membranes and typically cause less damage to the ECM (Rajab et al., 2020). Ionic detergents disrupt cellular membranes and have greater effects on protein interactions, so they disrupt the ECM more, thus weakening the collagen and other structural aspects of the membrane (Rajab et al., 2020). Zwitterionic detergents share properties with both ionic and nonionic ones, and they tend to denature proteins less than ionic detergents but more than nonionic detergents (Rajab et al., 2020). 

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The last type of decellularization protocol is biological via enzymatic reactions (Rajab et al., 2020). These typically occur with nucleases and proteases, which are combined in order to degrade both cells and ECM proteins (Rajab et al., 2020). The two must be carefully balanced for maximal decellularization and minimal degradation of the ECM (Rajab et al., 2020). 

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There are many alternative scaffolding materials that are currently being used and have been used before tissue decellularization came about, including emulsification, textiles, electrospinning, and 3D printing (Rajab et al., 2020). However, each has shortcomings that tissue-engineered scaffolds are able to overcome. For example, bioprinted scaffolds cannot reach a small enough size to model capillaries and other extremely small parts of organs and tissues in need of transplantation, while tissue-engineered ones can (Rajab et al., 2020). Emulsification is another type of scaffolding that provides high levels of porosity because of its creation process that includes droplets being used as templates that are subsequently removed to obtain porous qualities (Dikici et al, 2020). However, these tend to have issues with structural integrity because of their porous nature, so they are not as reliable as tissue engineering for alternative organ transplantation (Rajab et al., 2020).

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In order to successfully create tissue-engineered scaffolds that are able to be safely transplanted into humans, there are two categories they must satisfy: The scaffolds must be both non-toxic to all tissues in the body, and they must be biocompatible with all other structures (Rajab et al., 2020). However, if these criteria are satisfied, there will be significantly greater availability of tissue-engineered organ transplants for the tens of thousands of people who otherwise would not have been able to be treated. 

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The future of organ transplantation is bright with the possibility of tissue engineering, a much more accessible and personalized form of treatment than previous options. Successfully using decellularized scaffolding in patients would be a huge step toward bridging the gap of people who would have previously been denied organ transplantation.

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References 

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Aldemir Dikici, B., & Claeyssens, F. (2020). Basic principles of emulsion templating and its use as an emerging manufacturing method of tissue engineering scaffolds. Frontiers in Bioengineering and Biotechnology, 8. https://doi.org/10.3389/fbioe.2020.00875 

NCI Dictionary of Cancer terms. Comprehensive Cancer Information -NCI. (n.d.). https://www.cancer.gov/publications/dictionaries/cancer-terms/def/extracellular-matrix

Rajab, T. K., O’Malley, T. J., & Tchantchaleishvili, V. (2020). Decellularized scaffolds for tissue engineering: Current status and Future Perspective. Artificial Organs, 44(10), 1031–1043. https://doi.org/10.1111/aor.13701 

Yang, J., Bischof, J., Brockbank, K. G. M., Chang, W. G., Feng, H., Huling, J. C., Kedem, O., Mazur, P., Minami, T., Muldrew, K., Pegg, D., Raju, R., Schenke-Layland, K., Smith, A., Venkatasubramanian, R., Badylak, S. F., & Best, B. (2021, November 27). Effect of cryoprotectants on rat kidney decellularization by freeze-thaw process. Cryobiology. https://www.sciencedirect.com/science/article/pii/S0011224021003552#:~:text=To%20overcome%20the%20shortage%20of,are%20necessary%20for%20clinical%20applications.