The influence of surface micro-structure on endothelialization under supraphysiological wall shear stress

Robotti, Francesco; Franco, Davide; Bänninger, Livia; Wyler, J.; Starck, Christoph; Falk, Volkmar; Poulikakos, Dimos; Ferrari, Aldo

doi:10.1016/j.biomaterials.2014.06.046

Cited by 40 publications

(69 citation statements)

References 32 publications

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“…37 As shown now, EC seeded onto this surface (reference material) not only formed a confluent monolayer but also rearranged to align themselves to the direction of flow, thus establishing a characteristic polarization that is observable both in vivo and in vitro. [53][54][55] However, the Elastollan Õ material did not fulfill the mechanical properties required for usage in arterial grafts or a pump chambers in ventricular assist devices (data not shown). Instead, the PCU from the present study was more compatible as graft material, but after seeding of EC onto untreated and modified PCU grafts, shear stress caused loss of cell-cell-interactions of ECs which resulted in partial or complete removal of the cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to a compatible surface treatment for stable endothelialization, control of shear forces is inalienable in biocompatibility analysis of bioengineered grafts and vascular assist devices. 55 Future studies must include not only static tests but also standardized bioreactor systems that produced physiological flow streams before implantation into animals or humans. 60 The present study has some limitations.…”

Section: Discussionmentioning

confidence: 99%

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Plasma functionalization of polycarbonaturethane to improve endothelialization—Effect of shear stress as a critical factor for biocompatibility control

Lukas

Thomas²,

Gessner

et al. 2016

J Biomater Appl

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Medical devices made of polycarbonaturethane (PCU) combine excellent mechanical properties and little biological degradation, but restricted hemocompatibility. Modifications of PCU might reduce platelet adhesion and promote stable endothelialization. PCU was modified using gas plasma treatment, binding of hydrogels, and coupling of cellactive molecules (modified heparin, anti-thrombin III (ATIII), argatroban, fibronectin, laminin-nonapeptide, peptides with integrin-binding arginine-glycine-aspartic acid (RGD) motif). Biocompatibility was verified with static and dynamic cell culture techniques. Blinded analysis focused on improvement in endothelial cell (EC) adhesion/proliferation, antithrombogenicity, reproducible manufacturing process, and shear stress tolerance of ECs. EC adhesion and antithrombogenicity were achieved with 9/35 modifications. Additionally, 6/9 stimulated EC proliferation and 3/6 modification processes were highly reproducible for endothelialization. The latter modifications comprised immobilization of ATIII (A), polyethyleneglycole-diamine-hydrogel (E) and polyethylenimine-hydrogel connected with modified heparin (IH). Under sheer stress, only the IH modification improved EC adhesion within the graft. However, ECs did not arrange in flow direction and cell anchorage was restricted. Despite large variation in surface modification chemistry and improved EC adhesion under static culture conditions, additional introduction of shear stress foiled promising preliminary data. Therefore, biocompatibility testing required not only static tests but also usage of physiological conditions such as shear stress in the case of vascular grafts.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Plasma functionalization of polycarbonaturethane to improve endothelialization—Effect of shear stress as a critical factor for biocompatibility control

Lukas

Thomas²,

Gessner

et al. 2016

J Biomater Appl

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“…However, these approaches have had either partial or negligible effects on in-stent restenosis and thrombosis, 22 possibly because they led to incomplete endothelialization and/or because the restored EC layer was dysfunctional. Thus new strategies are required to promote endothelialization of stented arteries including novel surface chemistries 23 , 24 and compounds that enhance migration of EC to the stented segment.…”

Section: Discussionmentioning

confidence: 99%

Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase

Hsiao¹,

Spencer²,

Boldock³

et al. 2016

Cardiovasc Res

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AimsStent deployment causes endothelial cells (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow perturbation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration, we identified an intervention that promotes endothelial repair in stented arteries.Methods and ResultsIn vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (P < 0.01). To more closely mimic the in vivo situation, we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 μm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (P < 0.05). We investigated the effects of ROCK inhibition on re-endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re-endothelialization of stented carotid arteries (P < 0.05).ConclusionsStent struts delay endothelial repair by generating localized bidirectional flow which traps migrating EC. ROCK inhibitors accelerate endothelial repair of stented arteries by enhancing EC polarity and migration through regions of bidirectional flow.

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“…ECs exposed to high, physiological WSS (between 4 and 6 Pa) in the fully inflated state aligned perpendicular to the flow which is in agreement with what was previously reported (ref. 45 and Fig. 8).…”

Section: Resultsmentioning

confidence: 85%

“…Current endothelialization strategies that can be tested in the novel reactor system include rationally-designed surface topographies4345 promoting endothelial adhesion and migration (which can be introduced on the elastomeric membrane by means of standard soft lithography49, coatings with matrix proteins cross-linked to the elastomer50, or intervening layers of polymers deposited by means of electrospinning and directly bonded to the PDMS51). …”

Section: Discussionmentioning

confidence: 99%

A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces

Bachmann

Bernardi

Loosli

et al. 2016

Sci Rep

Self Cite

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The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.

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The influence of surface micro-structure on endothelialization under supraphysiological wall shear stress

Cited by 40 publications

References 32 publications

Plasma functionalization of polycarbonaturethane to improve endothelialization—Effect of shear stress as a critical factor for biocompatibility control

Plasma functionalization of polycarbonaturethane to improve endothelialization—Effect of shear stress as a critical factor for biocompatibility control

Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase

A Novel Bioreactor System for the Assessment of Endothelialization on Deformable Surfaces

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