Rheolution Article | December 2021
On the decellularization of organs to produce tissue-specific extracellular matrices for tissue engineering
by Dr. Dimitria Bonizol Camasao
Senior Application Specialist, Rheolution Inc.
During this last month, we focused on hydrogels based on decellularized extracellular matrices (dECM). As it has been discussed in the first publication of November 2021, dECM are great candidates for tissue engineering and regenerative medicine applications since they contain the natural biochemical cues and the right proportions of ECM proteins from the native ECM. This is important because they provide an optimal environment for cultivating cells in vitro aiming at mimicking native tissues for potential use in novel therapies. The second publication on this topic showed the soft nature of dECM derived from different porcine organs which is in accordance with the mechanical properties of organs and tissues.
But how exactly are these dECM obtained and used in research?
The image below illustrates the whole process from decellularization of an organ to production of a lab-grown engineered organ [1,2]. The first step (1) consists of removing all the organ’s cellular components to obtain just its extracellular matrix (ECM). The ECM is therefore composed of all non-cellular components of a tissue including their many types of proteins, proteoglycans and glycoproteins (protein binded with carbohydrates). The decellularization of organs is done using chemical, physical or biological methods [3]. Chemical methods involve the use of detergents to disrupt cell membranes and solubilize intracellular materials. Physical methods include high hydrostatic pressure, freeze-thaw cycles and supercritical CO2 which also provoke cell lysis (cell membrane disruption). Biological methods refer to specific enzymes that are used to break down cellular components.
The ECM of a specific tissue is then obtained after the decellularization process. There are two possibilities for the next step (2): (a) the dECM can be directly used with cells serving as an ideal scaffold that combine both the unique composition and architecture of a native tissue or (b) the dECM can be further processed and digested into a powder form which can be easily stored, transported and therefore commercialized. This last strategy has been more employed as a result of its easier scalability. The dECM powder can then be solubilized to form hydrogels (3) when researchers are ready to prepare their samples. These hydrogels can be used just as a 3D cell culture environment for cells to study different aspects of their behavior (differentiation, proliferation, phenotype) or processed with different techniques to produce more complex 3D shapes. The manufacturing techniques include but are not limited to casting, 3D printing and electrospinning.
When the aim is to produce a lab-grown organ, these hydrogels can be mixed with cells before or after shaped into the desired form (4). The organ-like structure needs to be matured to allow the cells to adhere, proliferate, and reorganize the many proteins present in these hydrogels in a more similar manner than it is naturally. This maturation process basically consists in leaving the samples in a biological incubator with a proper gas exchange and culture medium containing enough nutrients for its development.
For the mentioned reasons, dECM is one promising strategy to develop lab-grown organs. They have the potential to overcome the organ shortage for transplantation that we have always faced. Furthermore, they open many different possibilities for improving or developing novel treatments.
References
[1] Decellularization of tissues and organs for tissue engineering
[2] Tissue decellularization methods
[3] Gilbert, T. W., Sellaro, T. L., & Badylak, S. F. (2006). Decellularization of tissues and organs. Biomaterials, 27(19), 3675-3683.
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