Rheolution Article | December 2021
How are extracellular matrix of tissues obtained from organ decellularization and used in research?
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 . 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.
 Gilbert, T. W., Sellaro, T. L., & Badylak, S. F. (2006). Decellularization of tissues and organs. Biomaterials, 27(19), 3675-3683.
In October, our focus was on the mechanical characterization of soft organs. Understanding the mechanical properties of tissues is crucial for advancements in tissue engineering and regenerative medicine. However, measuring the mechanical properties of soft tissues is not straightforward and often involves customized approaches. Standardized and reproducible methods are needed to accurately characterize the mechanical properties of soft organs. By establishing consistent measurement techniques, researchers can gain a deeper understanding of tissue mechanics and develop effective treatments and therapies.
The emerging field of tissue engineering and regenerative medicine have the noble goal to develop lab-grown human tissues or alternative biomaterials to assist in their self-healing. In order to be functional in the human body, these biomaterials need to meet specific requirements of the intended site of implantation both in terms of biological, biochemical, and physical properties.
Mechanical testing of soft tissues and organs is crucial for biomaterial development. A study from the University of Massachusetts compared different testing techniques and evaluated the impact of sample freezing on lung tissue. The findings highlighted variations in mechanical properties depending on the technique used and showed a slight difference between fresh and frozen samples. Standardized testing methods are necessary for reliable measurements and advancements in tissue engineering.
In a recent study, researchers from the University of California at Davis investigated the impact of the viscoelasticity of the cell's environment on bone formation by mesenchymal stromal cells (MSCs). They prepared alginate hydrogels with different mechanical properties and loaded them with MSC aggregates. The results showed that while both hydrogels supported high cell viability, the viscoelastic hydrogel promoted significantly higher calcium production by the cells compared to the elastic hydrogel. Calcium is an essential component for bone regeneration. These findings emphasize the importance of the cell's external environment, specifically its viscoelastic properties, in influencing cellular behavior and tissue regeneration.
A research study conducted by the University of Delaware explored whether the physiological differences in the maturation of specific brain regions could explain the increased risk-taking tendencies during adolescence. The study, titled "Viscoelasticity of reward and control systems in adolescent risk-taking" and published in the Neuroimage Journal, proposed that risk-taking behaviors are influenced by two opposing brain systems: the reward system (socioemotional system) and the cognitive control system, responsible for regulating impulsive responses. Due to the chronological development of these systems, an imbalance may occur, potentially making adolescents more prone to engaging in risky activities.
Scars, which result from the wound healing process, exhibit differences in viscoelasticity compared to surrounding tissues. While skin scars may primarily affect aesthetics, scars in internal tissues and organs can impact their function. For example, scar formation in the heart muscle after a heart attack can lead to decreased muscular power and potential heart failure. It is important to note that viscoelastic behavior is inherent in all components of the body, and it plays a role in their physiological function. Cells, tissues, and organs exhibit both viscous (fluid-like) and elastic (solid-like) responses when subjected to mechanical forces. This viscoelastic response allows for deformation under force and gradual return to the original state once the force is removed.