Article of the month | October 2021
Measuring the viscoelastic properties of lungs through complementary techniques
by Dr. Dimitria Bonizol Camasao
Senior Application Specialist, Rheolution Inc.
In the development of new concrete materials that are more durable and environmentally friendly, civil engineers and scientists must determine its strength. One common technique that they perform is known as compressive testing. A cylindrical specimen made of fresh concrete is compressed at various ages between two plates. The strength of the concrete is the major factor that determines its quality, it is the basis of acceptance or rejection in construction. Insufficient strength can lead to costly, dangerous, and challenging repairs, or even failure of the construction. As concrete blocks and bricks are the structural elements of houses and buildings, tissues and organs are the structural and functional units of the human body. Therefore, determining their strength is also important to the development of biomaterials that are investigated to repair or replace them. To develop a better or a new medical implant, researchers need to know what they should target in terms of mechanical behavior.
There is not a standard mechanical testing method for soft tissues and organs. Most researchers customize the available mechanical testers and this is a major source of the wide results variation present in literature. This variation makes the understanding of the mechanobiological relationships challenging and impairs the development of biomaterials and bioengineered tissues. To assess how the Young modulus (common reported mechanical property) can vary among different techniques, a group of researchers from University of Massachusetts led by professor Shelly Peyton tested lung tissue using multiple characterization techniques such as micro-indentation, small amplitude oscillatory shear (SAOS), uniaxial tension, and cavitation rheology. In this study entitled “Cross-platform mechanical characterization of lung tissue”, the authors reported the average Young modulus obtained from various areas of the lung with each technique and their particularities [1].
Lung tissue has a delicate balance between strength and compliance which is essential for its repeated and massive expansion over the respiratory cycles. With the aim to detect and reduce the variations reported in the literature for this tissue, the first point evaluated by the authors was whether sample freezing (common preservation method) prior to the test can affect the final mechanical properties of the tissue. Fresh samples (not frozen) had a small but detectable higher value of Young’s modulus compared to samples frozen by different methods (liquid nitrogen, – 80 °C, and optimal cutting temperature medium). On the other hand, the effect of temperature (from 25 °C to 37 °C) had no significant effect on the samples’ moduli.
The authors then reported the average Young modulus of fresh lung specimens (4-20 specimens per lung in a total of 12 lungs) obtained using a novel technique (cavitation rheology) and three common methods found in literature (micro-indentation, SAOS and uniaxial tension). Briefly, cavitation rheology was performed using a custom-built instrument composed of a syringe pump, pressure sensors and a syringe needle responsible for injecting air inside the lung until a drop in pressure was attained (cavitation pressure). SAOS was performed using a standard rheometer with a flat plate geometry. Micro-indentation was done using a custom indenter with a flat cylindrical probe made from tool hardened steel and a deformable cantilever. Finally, uniaxial testing was carried out with a standard tensile tester (Fig. 1).
The authors observed that the modulus did vary depending on the testing method (even though they are within the same order of magnitude) and this is due to their inherent constraints (such as differences in sample preparation, sample geometry and region of the tissue that it had been taken, strain rate, temperature, and data processing). Cavitation rheology reported the stiffest moduli (6.1 ± 1.6 kPa), while SAOS led to the most compliant moduli (1.4 ± 0.4 kPa). The higher modulus obtained with the cavitation method was suggested to be the result of the fiber orientation during extension of the organ.
The group highlighted that micro-indentation, SAOS, and uniaxial generate a modulus for a small portion of the organ (small specimen excised from the organ) while in the cavitation method, almost the whole organ was used to obtain the modulus. Therefore, the authors believe that the last method generates a modulus that is more representative of the lung microstructure. Indeed, the heterogeneity of the lung tissue was seen with the higher range of measurements on individual samples using the cavitation rheology.
Overall, this study demonstrated the importance of recognizing that the little mechanical properties of soft organs reported in literature have inherent variations according to the testing method and customized protocol applied. A common method of characterization for soft organs is desirable to effectively facilitate the understanding of soft tissue mechanics and the development of biomaterials designed to repair or replace them.
References
[1] 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.
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.
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.
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.
