Mimicking the endothelial glycocalyx through the supramolecular presentation of hyaluronan on patterned surfaces

Pang, Xinqing; Li, Weiqi; Landwehr, Eliane; Yuan, Yichen; Wang, Wen; Azevedo, Helena S.

doi:10.1039/c9fd00015a

Cited by 14 publications

(39 citation statements)

References 54 publications

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“…Of note, age-related reduction in HA in the Bruch's membrane have been observed in human eyes [69]. Consistent with reports where short-chain HA deposits can direct and drive endothelial cell migration [68,70], our data shows that HYAL1 levels can mediate endothelial cell migration. Both increased barrier permeability and endothelial cell migration are processes linked to overall vascular instability.…”

Section: Discussionsupporting

confidence: 91%

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy

Yeo

et al. 2021

Preprint

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Background: Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis. Results: We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity through activation of Kruppel-like factor 2, a flow-responsive transcription factor, which in turn modulated PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples. Conclusions: Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.

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Section: Discussionsupporting

confidence: 91%

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy

Yeo

et al. 2021

Preprint

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“…For example, many groups have used poly(ethylene glycol) or glycosaminoglycans (GAGs) common to the glycocalyx, such as heparin (HEP), chondroitin sulfate (CS), and hyaluronan (HA), by conjugating them to substrate surfaces. [ 16,17,20–25 ] While these are multifunctional chemistries, studies using them are generally focused on only one important cell‐material interaction. Advancements have been made in the preparation of dual‐feature surfaces.…”

Section: Introductionmentioning

confidence: 99%

Blood‐Compatible Materials: Vascular Endothelium‐Mimetic Surfaces that Mitigate Multiple Cell‐Material Interactions

Vlcek

Hedayati

Melvin

et al. 2021

Adv Healthcare Materials

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When flowing whole blood contacts medical device surfaces, the most common blood–material interactions result in coagulation, inflammation, and infection. Many new blood‐contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood‐contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet‐, leukocyte‐, and bacteria‐surface interactions. This work demonstrates that new blood‐compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood‐contacting medical devices.

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“…Despite the known importance of the structural role, most of the studies supplement the cell culture medium with HA and thus examine HA in its soluble form. Cultivation of endothelial cells in gelatin/HA hydrogels or on HA coated surfaces revealed enhanced cell motility, robust cytoskeleton formation and altered CD44 expression ( Khanmohammadi et al, 2017 ; Pang et al, 2019 ). Next to the mode of presentation, the molecular weight (MW) of HA determines the complex physicochemical and biological properties of HA and its effects on angiogenesis and endothelial cell function.…”

Section: Discussionmentioning

confidence: 99%

Natural Presentation of Glycosaminoglycans in Synthetic Matrices for 3D Angiogenesis Models

Zapp

Mundinger

Boehm

2021

Front. Cell Dev. Biol.

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Glycosaminoglycans (GAGs) are long, linear polysaccharides that occur in the extracellular matrix of higher organisms and are either covalently attached to protein cores, as proteoglycans or in free form. Dependent on their chemical composition and structure, GAGs orchestrate a wide range of essential functions in tissue homeostasis. Accordingly, GAG-based biomaterials play a major role in tissue engineering. Current biomaterials exploit crosslinks between chemically modified GAG chains. Due to modifications along the GAG chains, they are limited in their GAG-protein interactions and accessibility to dissect the biochemical and biophysical properties that govern GAG functions. Herein, a natural presentation of GAGs is achieved by a terminal immobilization of GAGs to a polyethylene glycol (PEG) hydrogel. A physicochemical characterization showed that different end-thiolated GAGs can be incorporated within physiological concentration ranges, while the mechanical properties of the hydrogel are exclusively tunable by the PEG polymer concentration. The functional utility of this approach was illustrated in a 3D cell culture application. Immobilization of end-thiolated hyaluronan enhanced the formation of capillary-like sprouts originating from embedded endothelial cell spheroids. Taken together, the presented PEG/GAG hydrogels create a native microenvironment with fine-tunable mechanobiochemical properties and are an effective tool for studying and employing the bioactivity of GAGs.

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Mimicking the endothelial glycocalyx through the supramolecular presentation of hyaluronan on patterned surfaces

Abstract: Self-assembled monolayers of hyaluronan (HA)-binding peptide allow immobilization of HA for studying the function of the endothelial glycocalyx.

Cited by 14 publications

References 54 publications

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy

Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy

Blood‐Compatible Materials: Vascular Endothelium‐Mimetic Surfaces that Mitigate Multiple Cell‐Material Interactions

Natural Presentation of Glycosaminoglycans in Synthetic Matrices for 3D Angiogenesis Models

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