Complex Shear Modulus of Hydrogels Using a Dynamic Nanoindentation Method

Akhtar, Riaz; Draper, Emily R.; Adams, Dave J.; Pfaff, H.

doi:10.1007/978-3-319-21455-9_17

Cited by 9 publications

(6 citation statements)

References 12 publications

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“…A 3 × 3 array of indents with 200 μm spacing was generated. Tests were run as dynamic indentations to afford the complex shear modulus under the shear mode [ 33 ] at room temperature at a constant frequency of 110 Hz. Storage modulus G′ was measured as the energy stored during one oscillation cycle, and loss modulus G′′ was measured as the energy dissipated during an oscillation cycle [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

et al. 2018

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In calcific aortic valve disease (CAVD), microcalcifications originating from nanoscale calcifying vesicles disrupt the aortic valve (AV) leaflets, which consist of three (biomechanically) distinct layers: the fibrosa, spongiosa, and ventricularis. CAVD has no pharmacotherapy and lacks in vitro models as a result of complex valvular biomechanical features surrounding resident mechanosensitive valvular interstitial cells (VICs). We measured layer-specific mechanical properties of the human AV and engineered a three-dimensional (3D)-bioprinted CAVD model that recapitulates leaflet layer biomechanics for the first time. Human AV leaflet layers were separated by microdissection, and nanoindentation determined layer-specific Young’s moduli. Methacrylated gelatin (GelMA)/methacrylated hyaluronic acid (HAMA) hydrogels were tuned to duplicate layer-specific mechanical characteristics, followed by 3D-printing with encapsulated human VICs. Hydrogels were exposed to osteogenic media (OM) to induce microcalcification, and VIC pathogenesis was assessed by near infrared or immunofluorescence microscopy. Median Young’s moduli of the AV layers were 37.1, 15.4, and 26.9 kPa (fibrosa/spongiosa/ventricularis, respectively). The fibrosa and spongiosa Young’s moduli matched the 3D 5% GelMa/1% HAMA UV-crosslinked hydrogels. OM stimulation of VIC-laden bioprinted hydrogels induced microcalcification without apoptosis. We report the first layer-specific measurements of human AV moduli and a novel 3D-bioprinted CAVD model that potentiates microcalcification by mimicking the native AV mechanical environment. This work sheds light on valvular mechanobiology and could facilitate high-throughput drug-screening in CAVD.

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Section: Methodsmentioning

confidence: 99%

Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

et al. 2018

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“…In addition, at a 5-μm precompression depth, a punch diameter of 45.153 μm was calibrated. The nanoindentation experiments were run as dynamic indentations with a frequency of 110 Hz to allow for the complex shear modulus of soft materials like the hydrogel models ( 12 , 65 ). Indentations were performed at room temperature while keeping the hydrogel constructs moist by means of an air humidifier.…”

Section: Methodsmentioning

confidence: 99%

Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays

Clift,

Blaser,

Gerrits

et al. 2024

Sci. Adv.

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In calcific aortic valve disease (CAVD), mechanosensitive valvular cells respond to fibrosis- and calcification-induced tissue stiffening, further driving pathophysiology. No pharmacotherapeutics are available to treat CAVD because of the paucity of (i) appropriate experimental models that recapitulate this complex environment and (ii) benchmarking novel engineered aortic valve (AV)–model performance. We established a biomaterial-based CAVD model mimicking the biomechanics of the human AV disease-prone fibrosa layer, three-dimensional (3D)–bioprinted into 96-well arrays. Liquid chromatography–tandem mass spectrometry analyses probed the cellular proteome and vesiculome to compare the 3D-bioprinted model versus traditional 2D monoculture, against human CAVD tissue. The 3D-bioprinted model highly recapitulated the CAVD cellular proteome (94% versus 70% of 2D proteins). Integration of cellular and vesicular datasets identified known and unknown proteins ubiquitous to AV calcification. This study explores how 2D versus 3D-bioengineered systems recapitulate unique aspects of human disease, positions multiomics as a technique for the evaluation of high throughput–based bioengineered model systems, and potentiates future drug discovery.

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“…In order to ensure a consistent phase shift, the phase was monitored over a number of data points to exclude random spikes which would erroneously indicate contact. 35 However, once the surface detection requirement was fulfilled, the initial contact was set to the first point in that sequence.…”

Section: Nanoindentationmentioning

confidence: 99%

Oscillatory nanoindentation of highly compliant hydrogels: A critical comparative analysis with rheometry

et al. 2018

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Complex Shear Modulus of Hydrogels Using a Dynamic Nanoindentation Method

Cited by 9 publications

References 12 publications

Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

Engineering a 3D-Bioprinted Model of Human Heart Valve Disease Using Nanoindentation-Based Biomechanics

Intracellular proteomics and extracellular vesiculomics as a metric of disease recapitulation in 3D-bioprinted aortic valve arrays

Oscillatory nanoindentation of highly compliant hydrogels: A critical comparative analysis with rheometry

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