Rheolution Article
Are the mechanical characterization methods for organs comparable?
by Dr. Dimitria Bonizol Camasao
Senior Application Specialist, Rheolution Inc.
The month of October was focused on the mechanical characterization of soft organs. The characterization of healthy and diseased tissues is important in the field of tissue engineering and regenerative medicine to establish reference values of important mechanical properties (such as elastic/shear modulus, ultimate strength, ultimate strain) for the development of lab-grown human tissues or alternative biomaterials and therapies. Furthermore, the ex vivo mechanical characterization of treated tissues can give complementary information to standard imaging techniques in the course of in vivo studies of new drugs and technologies.

The mechanical characterization of soft tissues, however, is not straightforward. The measurement of their viscoelastic properties on standard mechanical testers, when possible, is often laborious and requires important customization steps (see our previous publication for specific examples). This leads to significant variation in the final method applied and in the properties reported in the literature. In order to illustrate the discrepancy one can find in the literature, the illustration below gathers measured elastic or shear modulus data of porcine lung tissues reported in published studies.

As shown in the image, lung tissues have been tested with ultrasound, micro-indentation, cavitation rheology, SAOS rheometry, uniaxial tension, magnetic resonance elastography, and viscoelastic testing of bilayered materials (VeTBiM). These many methods were found in just six studies so this list is still not complete. The range of values reported for the elastic and shear modulus of lung tissues can vary by a factor of 4. Furthermore, elastic modulus should be significantly higher than shear modulus (for example, the Young modulus equals three times the shear modulus) which is not really observed in these studies. It is possible to see that comparison among literature is challenging due to the inherent variations of the applied methods.
The lack of a standard method to measure the viscoelastic properties of soft organs impairs the development of the field. The quest for a robust method that can provide consistent data is therefore extremely valuable. Researchers need to know what they should target in terms of mechanical properties during the development of bioengineered tissues, novel biomaterials and therapies. For example, a heart valve implant produced with hard plastic will not perform as a soft and flexible natural valve. If this difference in viscoelastic properties is converted into reliable and standardized numbers, the arrival of these novel technologies into the market will definitely be facilitated.
References
[1] Cui, J., Lee, C. H., Delbos, A., McManus, J. J., & Crosby, A. J. (2011). Cavitation rheology of the eye lens. Soft Matter, 7(17), 7827-7831.
[2] Jansen, L. E., Birch, N. P., Schiffman, J. D., Crosby, A. J., & Peyton, S. R. (2015). Mechanics of intact bone marrow. Journal of the mechanical behavior of biomedical materials, 50, 299-307.
[3] Polio, S. R., Kundu, A. N., Dougan, C. E., Birch, N. P., Aurian-Blajeni, D. E., Schiffman, J. D., … & Peyton, S. R. (2018). Cross-platform mechanical characterization of lung tissue. PloS one, 13(10), e0204765.
[4] Mariappan, Y. K., Kolipaka, A., Manduca, A., Hubmayr, R. D., Ehman, R. L., Araoz, P., & McGee, K. P. (2012). Magnetic resonance elastography of the lung parenchyma in an in situ porcine model with a noninvasive mechanical driver: Correlation of shear stiffness with trans‐respiratory system pressures. Magnetic resonance in medicine, 67(1), 210-217.
[5] Hutchens, S. B., & Crosby, A. J. (2014). Soft-solid deformation mechanics at the tip of an embedded needle. Soft Matter, 10(20), 3679-3684.
[6] Rheolution Inc. (2021). Viscoelastic properties of porcine and sheep soft organs.
Related Posts
Decellularization is a process that removes cellular components from organs, leaving behind the extracellular matrix (ECM). This ECM, composed of proteins, proteoglycans, and glycoproteins, serves as a natural scaffold for tissue engineering applications. Decellularization can be achieved through chemical, physical, or biological methods. The resulting decellularized ECM, known as dECM, can be utilized to create hydrogels, bioinks, or coatings for enhancing cell adhesion and tissue regeneration.
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.