Rheological Characterization of in Situ Cross-Linkable Hyaluronan Hydrogels

Ghosh, Kaustabh; Shu, Xiao Zheng; Mou, Robert; Lombardi, Jack P.; Prestwich, Glenn D.; Rafailovich, Miriam; Clark, Richard A.F.

doi:10.1021/bm050361c

Cited by 152 publications

(177 citation statements)

References 33 publications

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“…Stiffness measurements were performed by using an AR-G2 rheometer (TA Instruments) with a standard aluminum parallel plate geometry of 20 mm. Hydrogels were subjected to a stress sweep (46), and their storage moduli (GЈ) were compared under the same physical conditions. To analyze the effects of varying ECM elasticity on cell shape, we cultured CE cells for 6 h on hydrogels of varying stiffness at a low density (1,000 cells per squared centimeter) to minimize cell-cell interactions.…”

Section: Methodsmentioning

confidence: 99%

Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro

Ghosh

Thodeti

Dudley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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179

187

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Tumor blood vessels exhibit abnormal structure and function that cause disturbed blood flow and high interstitial pressure, which impair delivery of anti-cancer agents. Past efforts to normalize the tumor vasculature have focused on inhibition of soluble angiogenic factors, such as VEGF; however, capillary endothelial (CE) cell growth and differentiation during angiogenesis are also influenced by mechanical forces conveyed by the extracellular matrix (ECM). Here, we explored the possibility that tumor CE cells form abnormal vessels because they lose their ability to sense and respond to these physical cues. These studies reveal that, in contrast to normal CE cells, tumor-derived CE cells fail to reorient their actin cytoskeleton when exposed to uniaxial cyclic strain, exhibit distinct shape sensitivity to variations in ECM elasticity, exert greater traction force, and display an enhanced ability to retract flexible ECM substrates and reorganize into tubular networks in vitro. These behaviors correlate with a constitutively high level of baseline activity of the small GTPase Rho and its downstream effector, Rho-associated kinase (ROCK). Moreover, decreasing Rho-mediated tension by using the ROCK inhibitor, Y27632, can reprogram the tumor CE cells so that they normalize their reorientation response to uniaxial cyclic strain and their ability to form tubular networks on ECM gels. Abnormal Rho-mediated sensing of mechanical cues in the tumor microenvironment may therefore contribute to the aberrant behaviors of tumor CE cells that result in the development of structural abnormalities in the cancer microvasculature.capillary ͉ contractility ͉ elasticity ͉ GTPase ͉ mechanotransduction

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Section: Methodsmentioning

confidence: 99%

Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro

Ghosh

Thodeti

Dudley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

179

187

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“…[164] Covalent in situ gelation chemistries, meanwhile, offer the dual benefits of fast reactions as well as more predictable and tunable degradation kinetics (or, in some cases, nondegradability) and as such have even broader potential utility. A variety of chemistries including amine-aldehyde (Schiff bases/imines), [165,166] thiol-thiol (disulfide), [167] hydrazide-aldehyde (hydrazones), [168,169] hydroxylamine-aldehyde (oximes), [170] thiol-maleimide (thiosuccinimides), [171] (thiol or amine)-alkene (Michael adducts), [172] and alkyne-azide (triazoles) [173] have been reported that meets the criteria of fast reactions that occur spontaneously upon mixing in water, with the chemistries listed above in the approximate order of the stability of the resulting crosslink in water.…”

Section: Solvent/additive-free Hydrogelsmentioning

confidence: 99%

Structured Macroporous Hydrogels: Progress, Challenges, and Opportunities

Hoare

2017

Adv Healthcare Materials

171

168

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Structured macroporous hydrogels that have controllable porosities on both the nanoscale and the microscale offer both the swelling and interfacial properties of bulk hydrogels as well as the transport properties of “hard” macroporous materials. While a variety of techniques such as solvent casting, freeze drying, gas foaming, and phase separation have been developed to fabricate structured macroporous hydrogels, the typically weak mechanics and isotropic pore structures achieved as well as the required use of solvent/additives in the preparation process all limit the potential applications of these materials, particularly in biomedical contexts. This review highlights recent developments in the field of structured macroporous hydrogels aiming to increase network strength, create anisotropy and directionality within the networks, and utilize solvent‐free or additive‐free fabrication methods. Such functional materials are well suited for not only biomedical applications like tissue engineering and drug delivery but also selective filtration, environmental sorption, and the physical templating of secondary networks.

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“…In the absence of AuNPs, soft disulfi de-crosslinked gels with a G ′ , or storage modulus, of 10-20 Pa form. [ 11 ] First, to confi rm biocompatibility, a LIVE/DEAD viability/ cytotoxicity assay and an MTS mitochondrial activity assay was performed on cells cultured on the surface of AuNP-sECM hydrogels. NIH 3T3, HepG2 C3A, and Int-407 cells showed > 95% viability at day 3 and at day 7 (Supporting Information, Figure S1).…”

Section: Doi: 101002/adma201001436mentioning

confidence: 99%