Blood coagulation on biomaterials requires the combination of distinct activation processes

Sperling, Claudia; Fischer, Marion; Maitz, Manfred F.; Werner, Carsten

doi:10.1016/j.biomaterials.2009.05.044

Cited by 243 publications

(253 citation statements)

References 57 publications

Supporting

Mentioning

247

Contrasting

Order By: Relevance

“…FXI, to induce thrombus formation. Artificial surfaces, including tygon tubing used in the vascular shunt, promote fibrinogen and platelet deposition along with activation of intrinsic coagulation [40,41]. The strong antithrombotic activity of BMS-262084 in the AVST model may be related to FXIa formation and participation in thrombus formation in this setting.…”

Section: Discussionmentioning

confidence: 96%

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

Wong

Crain

Watson

et al. 2011

J Thromb Thrombolysis

View full text Add to dashboard Cite

BMS-262084 is a 4-carboxy-2-azetidinone-containing irreversible inhibitor of FXIa, which is selective over other coagulation proteases. We evaluated the in vitro and in vivo properties of BMS-262084 in rabbits. Studies were conducted in arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), electrolytic-mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. BMS-262084 was infused IV from 1 h before thrombus induction or cuticle transection to the end of the experiment. In vitro, BMS-262084 prolonged activated partial thromboplastin time (aPTT) with EC(2x) (concentration required to double aPTT) of 10.6 μM in rabbit plasma, and did not prolong prothrombin time (PT), thrombin time (TT) and HepTest. In vivo, BMS-262084 produced dose-dependent antithrombotic effects in rabbits with antithrombotic ED(50) (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT of 0.4, 0.7 and 1.5 mg/kg/h IV, respectively. BMS-262084 increased ex vivo aPTT dose-dependently without changes in PT and TT. The antithrombotic effect of BMS-262084 was significantly correlated with its ex vivo aPTT, supporting the use of ex vivo aPTT as a pharmacodynamic biomarker. BMS-262084 did not alter ex vivo rabbit platelet aggregation to ADP and collagen. BT (fold-increase) determined at 3 and 10 mg/kg/h of BMS-262084 were 1.17 ± 0.04 and 1.52 ± 0.07*, respectively (*P < 0.05 vs. control). This study demonstrated that BMS-262084 prevented experimental thrombosis at doses with low BT effects in rabbits, and suggests that a small molecule FXIa inhibitor may represent a promising antithrombotic therapy.

show abstract

Section: Discussionmentioning

confidence: 96%

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

Wong

Crain

Watson

et al. 2011

J Thromb Thrombolysis

View full text Add to dashboard Cite

show abstract

“…Ordered and well-controlled surface functional groups (-CH 3 , -COOH, -OH and -NH 2 ) grafted on SAMs induced changes of wettability and were used to study cell adhesion behaviour and correlate it with the FAK signalling pathway [34], and adsorption and activation of plasma proteins (fibrinogen and albumin) [37]. According to these studies [38], the surfaces prepared with different concentrations (100/0, 34/66, 50/50, 83/17, 0/100) of two kinds of thiol (HS-(CH 2 ) 10 -CH 3 and HS-(CH 2 ) 10 -COOH) had contact angles from 111 + 3.58 to 21 + 7.18, which were in a similar range to that of the SiO x :H plasma nanocoating surfaces used in the present study. The literature results showed that the number of adhered HUVECs reached a maximum on CH 3 /OH-mixed SAMs with a water contact angle of 408, while cell adhesion decreased with increasing water contact angle up to 60-708, suggesting that cell adhesion is mainly determined by surface wettability, but is also affected by the surface functional groups, their surface density and the cell type [13].…”

Section: Discussionmentioning

confidence: 99%

Surface wettability of plasma SiO _x :H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways

Shen

Wang

Huang

et al. 2011

J. R. Soc. Interface.

View full text Add to dashboard Cite

Vascular endothelial cell (EC) adhesion and migration are essential processes in re-endothelialization of implanted biomaterials. There is no clear relationship and mechanism between EC adhesion and migration behaviour on surfaces with varying wettabilities. As model substrates, plasma SiO x :H nanocoatings with well-controlled surface wettability (with water contact angles in the range of 98.5 + 2.38 to 26.3 + 4.08) were used in this study to investigate the effects of surface wettability on cell adhesion/migration and associated protein expressions in FAK-Rho GTPases signalling pathways. It was found that EC adhesion/migration showed opposite behaviour on the hydrophilic and hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397 site of FAK could significantly inhibit cell adhesion/migration, suggesting that EC adhesion and migration on surfaces with different wettabilities involve ( p)FAK and its downstream signalling pathways. Western blot results suggested that the FAK-Rho GTPases signalling pathways were correlative to EC migration on hydrophobic plasma SiO x :H surfaces, but uncertain to hydrophilic surfaces. This work demonstrated that surface wettability could induce cellular behaviours that were associated with different cellular signalling events.

show abstract

“…[8] The interaction between blood constituents and polymer materials has been addressed by numerous authors. [9][10][11][12][13][14] Although the exact mechanisms are not known, recent advances allow formation of a simplified picture. Immediately after polymer material contacts human blood the molecules present in blood will interact with the polymer surfaces.…”

Section: Introductionmentioning

confidence: 99%

Morphology Transformations of Platelets on Plasma Activated Surfaces

Modić

Junkar

Stana‐Kleinschek

et al. 2014

Plasma Processes & Polymers

View full text Add to dashboard Cite

Improved hemocompatibility from the perspective of platelets adhesion and activation on polyethylene terephthalate surfaces has been addressed. The activation stage of platelets has been determined from their size and morphology using scanning electron microscopy (SEM). The activation of platelets on untreated polymer materials was very intensive. Polymer materials were treated with weakly ionized oxygen plasma in order to repel platelet adhesion. Already short treatment times (3s) showed significant reduction of the total number and of highly activated forms of adhered platelets. Possible mechanisms of different behaviour of blood platelets on plasma treated polymer were discussed in terms of surface adhesion and changes in morphology.

show abstract

Blood coagulation on biomaterials requires the combination of distinct activation processes

Cited by 243 publications

References 57 publications

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

Surface wettability of plasma SiO _x :H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways

Morphology Transformations of Platelets on Plasma Activated Surfaces

Contact Info

Product

Resources

About

Blood coagulation on biomaterials requires the combination of distinct activation processes

Cited by 243 publications

References 57 publications

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

A small-molecule factor XIa inhibitor produces antithrombotic efficacy with minimal bleeding time prolongation in rabbits

Surface wettability of plasma SiO x :H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways

Morphology Transformations of Platelets on Plasma Activated Surfaces

Contact Info

Product

Resources

About

Surface wettability of plasma SiO _x :H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways