Three-dimensional 10% cyclic strain reduces bovine aortic endothelial cell angiogenic sprout length and augments tubulogenesis in tubular fibrin hydrogels

Gassman, Andrew; Kuprys, Tomas; Ucuzian, Areck A.; Brey, Eric M.; Matsumura, Akie; Pang, Yue; Larson, Jef; Greisler, Howard P.

doi:10.1002/term.323

Cited by 10 publications

(11 citation statements)

References 38 publications

(49 reference statements)

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“…On the other hand, substrates such as fibrin and Matrigel resulted in the inhibition of angiogenic responses with strain application, including decreased network lengths and diminished network branching (19,38,58). The responses varied between two-and three-dimensional cultures (19,58,64). Overall, these studies suggest that, at least for nondiabetic endothelial cells, substrate may mediate strain-induced alterations in angiogenic cell responses.…”

Section: Discussionmentioning

confidence: 81%

“…Substrates such as collagen, gelatin, fibronectin, pronectin, and silicone elastomers appeared to stimulate angiogenic responses, resulting in increased levels of VEGF, MMP-2, and enhanced proliferation and vascular network formation (28,56,62,64). On the other hand, substrates such as fibrin and Matrigel resulted in the inhibition of angiogenic responses with strain application, including decreased network lengths and diminished network branching (19,38,58). The responses varied between two-and three-dimensional cultures (19,58,64).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro studies have shown that cyclic strain influences the angiogenic responses of endothelial cells, including the effects on vascular network formation, cell apoptosis, migration and proliferation, and various growth factors, enzymes, genes, and proteins related to angiogenesis (19,21,28,36,38,57,58,63,64). In addition, the angiogenic responses of cells subjected to strain depend on the substrate used to culture the cells (19,38,57,58,64). A summary of the results from these studies is organized by substrate type in Table 1 and includes the cell types, strain parameters, and angiogenic responses.…”

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confidence: 99%

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Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Sheikh

Kuesel

Taghian

et al. 2014

American Journal of Physiology-Cell Physiology

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Diabetes-induced cardiomyopathy is characterized by cardiac remodeling, fibrosis, and endothelial dysfunction, with no treatment options currently available. Hyperglycemic memory by endothelial cells may play the key role in microvascular complications in diabetes, providing a potential target for therapeutic approaches. This study tested the hypothesis that a proangiogenic environment can augment diabetes-induced deficiencies in endothelial cell angiogenic and biomechanical responses. Endothelial responses were quantified for two models of diabetic conditions: 1) an in vitro acute and chronic hyperglycemia where normal cardiac endothelial cells were exposed to high-glucose media, and 2) an in vivo chronic diabetes model where the cells were isolated from rats with type I streptozotocin-induced diabetes. Capillary morphogenesis, VEGF and nitric oxide expression, cell morphology, orientation, proliferation, and apoptosis were determined for cells cultured on Matrigel or proangiogenic nanofiber hydrogel. The effects of biomechanical stimulation were assessed following cell exposure to uniaxial strain. The results demonstrate that diabetes alters cardiac endothelium angiogenic response, with differential effects of acute and chronic exposure to high-glucose conditions, consistent with the concept that endothelial cells may have a long-term “hyperglycemic memory” of the physiological environment in the body. Furthermore, endothelial cell exposure to strain significantly diminishes their angiogenic potential following strain application. Both diabetes and strain-associated deficiencies can be augmented in the proangiogenic nanofiber microenvironment. These findings may contribute to the development of novel approaches to reverse hyperglycemic memory of endothelium and enhance vascularization of the diabetic heart, where improved angiogenic and biomechanical responses can be the key factor to successful therapy.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Sheikh

Kuesel

Taghian

et al. 2014

American Journal of Physiology-Cell Physiology

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“…Similar cyclic strain conditions induced sprouting parallel to the stretching direction, whereas radial sprouting was observed in unstrained constructs [59]. While cyclic strain was shown to influence sprouting orientation, another study reported that cyclic strain reduces the length and density of sprouting, yielding wider and less branched sprouts [60].…”

Section: External Forcesmentioning

confidence: 95%

Mechanical regulation of vascular network formation in engineered matrices

Lesman

Rosenfeld

Landau

et al. 2016

Advanced Drug Delivery Reviews

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“…Thus, decoupling stiffness from these other variables is essential to evaluate cell behavior properly as a function of gel concentration [34]. A number of approaches have been used to isolate the independent contribution of stiffness, such as altering mechanical boundary conditions [30,35,36], crosslinking [37–39] or composition [32,40–42]. While such approaches to control stiffness in natural polymers have many merits, they are often limited by the interdependence of fiber size, pore size and stiffness, as well as an inability to control both matrix stiffness and binding site density.…”

Section: Introductionmentioning

confidence: 99%

A self-assembling peptide matrix used to control stiffness and binding site density supports the formation of microvascular networks in three dimensions

et al. 2013

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A three-dimensional (3-D) cell culture system that allows control of both substrate stiffness and integrin binding density was created and characterized. This system consisted of two self-assembling peptide (SAP) sequences that were mixed in different ratios to achieve the desired gel stiffness and adhesiveness. The specific peptides used were KFE ((acetyl)-FKFEFKFE-CONH2), which has previously been reported not to support cell adhesion or MVN formation, and KFE-RGD ((acetyl)-GRGDSP-GG-FKFEFKFE-CONH2), which is a similar sequence that incorporates the RGD integrin binding site. Storage modulus for these gels ranged from ~60 to 6000 Pa, depending on their composition and concentration. Atomic force microscopy revealed ECM-like fiber microarchitecture of gels consisting of both pure KFE and pure KFE-RGD as well as mixtures of the two peptides. This system was used to study the contributions of both matrix stiffness and adhesiveness on microvascular network (MVN) formation of endothelial cells and the morphology of human mesenchymal stem cells (hMSC). When endothelial cells were encapsulated within 3-D gel matrices without binding sites, little cell elongation and no network formation occurred, regardless of the stiffness. In contrast, matrices containing the RGD binding site facilitated robust MVN formation, and the extent of this MVN formation was inversely proportional to matrix stiffness. Compared with a matrix of the same stiffness with no binding sites, a matrix containing RGD-functionalized peptides resulted in a ~2.5-fold increase in the average length of network structure, which was used as a quantitative measure of MVN formation. Matrices with hMSC facilitated an increased number and length of cellular projections at higher stiffness when RGD was present, but induced a round morphology at every stiffness when RGD was absent. Taken together, these results demonstrate the ability to control both substrate stiffness and binding site density within 3-D cell-populated gels and reveal an important role for both stiffness and adhesion on cellular behavior that is cell-type specific.

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Three-dimensional 10% cyclic strain reduces bovine aortic endothelial cell angiogenic sprout length and augments tubulogenesis in tubular fibrin hydrogels

Cited by 10 publications

References 38 publications

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Angiogenic microenvironment augments impaired endothelial responses under diabetic conditions

Mechanical regulation of vascular network formation in engineered matrices

A self-assembling peptide matrix used to control stiffness and binding site density supports the formation of microvascular networks in three dimensions

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