These approaches can map the spatial mechanical heterogeneity in a tissue region based on the differential deformation within a specific volume. Ultrasound techniques that use acoustic radiation force (ARF) to induce deformation to a sample have been exploited as a non-invasive strategy to evaluate both the static and dynamic mechanical properties of biomaterials and tissues. Therefore, there is a need for methods capable of longitudinal tracking of the mechanical properties of these materials as they change over various time scales.
In addition, the viscoelastic properties of hydrogels are rarely static, as they undergo continuous change due to swelling, enzymatic degradation or crosslinking, and in some cases cell-mediated remodeling. However, the deformation required by these techniques is generally achieved by physical contact, which can result in contamination and damage, thereby limiting these approaches to a single end-point measurement for each sample. The viscoelastic behavior can be assessed from time-dependent material responses, such as creep and stress relaxation. Each of these methods operates by applying a defined deformation or force to a sample and then measuring the material response. Common material testing approaches include tension, compression, indentation, and shear-based approaches. Therefore, the capability to measure and analyze the viscoelastic properties of biomaterials is important in tissue engineering applications.Ĭompared to solid polymers or metals, mechanical testing of hydrogels can be particularly challenging due to their relatively low elastic modulus, viscoelastic nature, and biphasic structure. Both the elastic and viscous components of the extracellular matrix have been implicated as important effectors in controlling cell function. Their mechanical properties can vary widely despite the high volume-percentage of water common to all hydrogel materials. Hydrogels can be made from a wide variety of natural and synthetic polymers and can be modified to exhibit specific biochemical cues for regulating cellular phenotype. These biomaterials consist primarily of water-infused networks of hydrophilic polymer chains and are typically soft and viscoelastic.
To this end, hydrogels have been used extensively in the field of tissue engineering as a synthetic extracellular matrix, providing a valuable biomaterial platform to recapitulate the structure and function of a variety of biological tissues.
The mechanical properties of the cellular microenvironment are an important regulator of cellular phenotype. Overall, these studies demonstrate that RAR can be a valuable tool to noninvasively quantify the viscoelastic mechanical properties of soft hydrogel biomaterials. Importantly, RAR circumvents some limitations of conventional rheology methods and can be performed in a high-throughput manner using conventional labware. Application of RAR was verified using finite element modeling and the results were validated against rotational shear rheometry. RAR was also used to longitudinally track dynamic changes in viscoelastic properties over the course of fibrin gelation, revealing distinct phase and material property transitions. Single time point measurements of gelled samples with static mechanical properties showed that RAR provided consistent quantitative data and measured intrinsic material characteristics independent of ultrasound parameters. In this study, RAR was used to characterize fibrin, gelatin, and agarose hydrogels. The frequency spectrum of the resonant surface waves is analyzed to extract viscoelastic material properties. RAR uses a focused ultrasound pulse to generate a microscale perturbation at the sample surface and tracks the ensuing surface wave using pulse-echo ultrasound. Resonant Acoustic Rheometry (RAR) is a new, non-contact technique to characterize the mechanical properties of soft and viscoelastic biomaterials, such as hydrogels, that are used to mimic the extracellular matrix in tissue engineering.
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