Hydrogel Network Dynamics Regulate Vascular Morphogenesis

Zhao, Wei; Schnellmann, Rahel; Pruitt, Hawley C.; Gerecht, Sharon

doi:10.1016/j.stem.2020.08.005

Cited by 104 publications

(88 citation statements)

References 94 publications

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“…Facilitating sprout-mediated matrix remodeling by modulating synthetic hydrogel degradability could augment sprout diameters via proteolysis but at the cost of also enhancing resorption rates. Viscoelastic hydrogels could take advantage of proteolysis-independent methods of space generation via cell force-mediated pushing forces, as previous studies have demonstrated plastic deformation of hydrogels with viscoelastic behavior ( Chaudhuri et al, 2020 ; Wei et al, 2020 ). As increased EC proliferation resulted in enhanced sprout diameters, incorporating matrix cues that additionally enhance proliferation in 3D synthetic hydrogel settings would also be beneficial.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Endothelial Stalk Cell–Matrix Interactions Regulate Angiogenic Sprout Diameter

Wang

Jarman

Lin

et al. 2021

Front. Bioeng. Biotechnol.

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Angiogenesis is a complex, multicellular process that involves bidirectional interactions between extracellular matrix (ECM) and collectively invading endothelial cell (EC) sprouts that extend the microvasculature during development, wound healing, and disease processes. While many aspects of angiogenesis have been well studied, the relationship between endothelial sprout morphology and subsequent neovessel function remains relatively unknown. Here, we investigated how various soluble and physical matrix cues that regulate endothelial sprouting speed and proliferation correspond to changes in sprout morphology, namely, sprout stalk diameter. We found that sprout stalk cells utilize a combination of cytoskeletal forces and proteolysis to physically compact and degrade the surrounding matrix, thus creating sufficient space in three-dimensional (3D) ECM for lateral expansion. As increasing sprout diameter precedes lumenization to generate perfusable neovessels, this work highlights how dynamic endothelial stalk cell–ECM interactions promote the generation of functional neovessels during sprouting angiogenesis to provide insight into the design of vascularized, implantable biomaterials.

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Section: Discussionmentioning

confidence: 99%

Dynamic Endothelial Stalk Cell–Matrix Interactions Regulate Angiogenic Sprout Diameter

Wang

Jarman

Lin

et al. 2021

Front. Bioeng. Biotechnol.

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“…Besides, viscoelastic hydrogel network regulated vascular morphogenesis‐related phenotype changes (Figure 13C). [ 207 ] Human endothelial colony‐forming cells (ECFCs) were encapsulated in elastic non‐dynamic network hydrogels (N‐hydrogels) and viscoelastic dynamic networked hydrogels (D‐hydrogels), respectively. Although vacuoles formed in both N‐ and D‐hydrogels within 4–8 h, sprouting and branching of ECFCs markedly differed after 1 day, showing differently modulated phenotype changes of ECFCs.…”

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior Andmentioning

confidence: 99%

Section: Viscoelastic Cell Microenvironment Affects Cell Behavior Andmentioning

confidence: 99%

“…Recently, it has been gradually revealed some pathways associated with cellular responses to viscoelastic microenvironment ( Figure ). [ 18,51,197,207,208 ] However, most pathways have focused on integrin‐based mechanosensitive receptor, actomyosin contractility, and YAP/TAZ nuclear localization. In fact, mechanosensing and mechanotransduction processes are definitely more complicated.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Han

Yang

et al. 2021

Adv Funct Materials

Self Cite

112

121

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The native extracellular matrix (ECM) generally exhibits dynamic mechanical properties and displays time‐dependent responses to deformation or mechanical loading, in terms of viscoelastic behaviors (e.g., stress relaxation and creep). Viscoelasticity of the ECM plays a critical role in development, homeostasis, and tissue regeneration, and its implication in disease progression has also been recognized recently. Hydrogels with tunable viscoelastic properties hold a great promise to recapitulate such time‐dependent mechanics found in native ECM, which have been recently used to regulate cell behavior and guide cell fate. Here the importance of tissue viscoelasticity is first highlighted, the molecular mechanisms of hydrogel viscoelasticity are summarized, and characterization techniques used at the macroscale and microscale are reviewed. Then, recent advances in developing novel hydrogels with tunable viscoelasticity through varying crosslinking strategies, engineering of viscoelastic cell microenvironment and its substantial effects on cell behavior and fate are described, and the underlying mechanobiology mechanisms are subsequently discussed. Finally, the ongoing challenges and future perspectives on the design and modulation of viscoelastic hydrogels and the mechanobiology mechanisms on cellular responses to viscoelastic cell microenvironment are proposed.

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“…Matrix stiffness and cyclic compression could increase angiogenesis via inducing secretion of VEGF from human mesenchymal stem cells via Yes-associated protein (YAP) pathway ( Bandaru et al, 2020 ). Dynamic hydrogels could induce clustering of integrin β1 and MMP expression to promote angiogenesis ( Wei et al, 2020 ). Metastasis-associated fibroblasts could increase ECM stiffness ( Shen et al, 2020 ).…”

Section: Aats and Aat Resistance Mechanismsmentioning

confidence: 99%

Resistance Mechanisms of Anti-angiogenic Therapy and Exosomes-Mediated Revascularization in Cancer

Zeng

2020

Front. Cell Dev. Biol.

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Anti-angiogenic therapies (AATs) have been widely used for cancer treatment. But the beneficial effects of AATs are short, because AAT-induced tumor revascularization facilitates the tumor relapse. In this mini-review, we described different forms of tumor neovascularization and revascularization including sprouting angiogenesis, vessel co-option, intussusceptive angiogenesis, and vasculogenic mimicry, all of which are closely mediated by vascular endothelial growth factor (VEGF), angiopoietins, matrix metalloproteinases, and exosomes. We also summarized the current findings for the resistance mechanisms of AATs including enhancement in pro-angiogenic cytokines, heterogeneity in tumor-associated endothelial cells (ECs), crosstalk between tumor cells and ECs, masking of extracellular vesicles, matrix stiffness and contributions from fibroblasts, macrophages and adipocytes in the tumor microenvironment. We highlighted the revascularization following AATs, particularly the role of exosome stimulating factors such as hypoxia and miRNA, and that of exosomal cargos such as cytokines, miRNAs, lncRNAs, and circRNAs from the tumor ECs in angiogenesis and revascularization. Finally, we proposed that renormalization of tumor ECs would be a more efficient cancer therapy than the current AATs.

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Hydrogel Network Dynamics Regulate Vascular Morphogenesis

Cited by 104 publications

References 94 publications

Dynamic Endothelial Stalk Cell–Matrix Interactions Regulate Angiogenic Sprout Diameter

Dynamic Endothelial Stalk Cell–Matrix Interactions Regulate Angiogenic Sprout Diameter

Viscoelastic Cell Microenvironment: Hydrogel‐Based Strategy for Recapitulating Dynamic ECM Mechanics

Resistance Mechanisms of Anti-angiogenic Therapy and Exosomes-Mediated Revascularization in Cancer

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