Reactive Ion Plasma Modification of Poly(Vinyl‐Alcohol) Increases Primary Endothelial Cell Affinity and Reduces Thrombogenicity

Anderson, Deirdre E.J.; Pohan, Grace; Yim, Evelyn K.F.; Hinds, Monica T.

doi:10.1002/mabi.201800132

Cited by 16 publications

(28 citation statements)

References 36 publications

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“…In the whole blood ex vivo model without antiplatelet drugs, the plain PVA trended to the lowest platelet accumulation, supporting previous work that PVA has potential as a nonthrombogenic cardiovascular biomaterial. [14,33] An increase in platelet adhesion was seen for GFPGER-modified PVA compared to ePTFE, yet ePTFE had significantly more fibrin deposition when no antiplatelet drugs were used. To study the translatability of PVA with the endothelialization-promoting GFPGER modification, we tested the thrombogenicity of this material using clinically relevant antiplatelet therapies: ASA or DAPT.…”

Section: Discussionmentioning

confidence: 99%

“…After 48hrs of cell incubation, samples were stained using standard immunofluorescence procedures, as described previously. [33] Briefly, films were fixed and stained with Alexa Fluor ® 568 phalloidin, a primary VE-Cadherin antibody and secondary IgG1 Alexa-488, and DAPI. Films were mounted onto glass slides and imaged with a Nikon Ellipse TE-200U fluorescent microscope.…”

Section: Fluorescent Stainingmentioning

confidence: 99%

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Biomimetic modification of poly(vinyl alcohol): Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy

et al. 2019

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Poly(vinyl alcohol) (PVA) has shown promise as a biomaterial for cardiovascular application. However, its antifouling properties prevent in vivo endothelialization. This work examined the endothelialization and thrombogenicity of modified PVA with different concentrations of proteins and adhesion peptides: collagen, laminin, fibronectin, GFPGER, YIGSR, and cRGD. Material surface properties were quantified, and the endothelialization potential was determined with human endothelial colony forming cells. Additionally, platelet attachment was assessed in vitro with human platelet rich plasma, and promising samples were tested in an ex vivo shunt model. This well-established arteriovenous shunt model was used with and without clinically-relevant antiplatelet therapies, specifically acetylsalicylic acid (ASA) with and without clopidogrel to examine the minimum necessary treatment to prevent thrombosis. Collagen, laminin, and GFPGER biomolecules increased endothelialization, with GFPGER showing the greatest effect at the lowest concentrations. GFPGER-PVA tubes tested under whole blood did exhibit an increase in platelet (but not fibrin) attachment compared to plain PVA and clinical controls. However, application of ASA monotherapy reduced the thrombogenicity of GFPGER-PVA below the clinical control with the ASA. This work is significant in developing cardiovascular biomaterials-increasing endothelialization potential while reducing bleeding side effects by using an antiplatelet monotherapy, typical of clinical patients.

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Section: Discussionmentioning

confidence: 99%

Section: Fluorescent Stainingmentioning

confidence: 99%

Biomimetic modification of poly(vinyl alcohol): Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy

et al. 2019

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“…Previous in vitro cell adhesion studies with plasma treated PVA films have shown to improve endothelial cell attachment on the PVA treated with N 2 /H 2 , N 2 , O 2 , or Ar plasma (Ino et al, 2013; Cutiongco et al, 2016a; Jurney et al, 2018). These cell adhesion studies were conducted in a short term (2–6 days), and the plasma treatments were performed on flat surfaces or on the external surface of a tube.…”

Section: Introductionmentioning

confidence: 97%

“…The exposure of these surfaces to ionized gas leads to incorporation of chemical species, which results in surface functionalization. For example, it was previously reported that the wettability of plasma treated surfaces improves after the treatment to favor either bonding of coating material or cell adhesion (Nakagawa et al, 2006; Jacobs et al, 2012; Ino et al, 2013; Liu et al, 2014; Cutiongco et al, 2016a; Recek et al, 2016; Jurney et al, 2018). Depending on the gas type and the material that is interacting with the plasma, one can introduce different surface functional groups on the biomaterial surface.…”

Section: Introductionmentioning

confidence: 99%

Luminal Plasma Treatment for Small Diameter Polyvinyl Alcohol Tubular Scaffolds

Pohan

Chevallier

Anderson

et al. 2019

Front. Bioeng. Biotechnol.

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Plasma-based surface modification is recognized as an effective way to activate biomaterial surfaces, and modulate their interactions with cells, extracellular matrix proteins, and other materials. However, treatment of a luminal surface of a tubular scaffold remains non-trivial to perform in small diameter tubes. Polyvinyl alcohol (PVA) hydrogel, which has been widely used for medical applications, lacks functional groups to mediate cell attachment. This poses an issue for vascular applications, as endothelialization in a vascular graft lumen is crucial to maintain long term graft patency. In this study, a Radio Frequency Glow Discharges (RFGD) treatment in the presence of NH 3 was used to modify the luminal surface of 3-mm diameter dehydrated PVA vascular grafts. The grafted nitrogen containing functional groups demonstrated stability, and in vitro endothelialization was successfully maintained for at least 30 days. The plasma-modified PVA displayed a higher percentage of carbonyl groups over the untreated PVA control. Plasma treatment on PVA patterned with microtopographies was also studied, with only the concave microlenses topography demonstrating a significant increase in platelet adhesion. Thus, the study has shown the possibility of modifying a small diameter hydrogel tubular scaffold with the RFGD plasma treatment technique and demonstrated stability in ambient storage conditions for up to 30 days.

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“…Our group has used a whole blood, ex vivo shunt model for many decades to evaluate the hemocompatibility of cardiovascular biomaterials [8][9][10][11][12][13]. The ability to control flow rate and local or systemic drugs makes the ex vivo whole blood shunt model very powerful for potential clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Quantifying Physical Thrombus Characteristics on Cardiovascular Biomaterials Using MicroCT

Gupta

Johnston

Hinds

et al. 2020

MPs

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Hemocompatibility is a critical consideration when designing cardiovascular devices. Methods of assessing hemocompatibility range from in vitro protein adsorption and static platelet attachment to in vivo implantation. A standard preclinical assessment of biomaterial hemocompatibility is ex vivo quantification of thrombosis in a chronic arteriovenous shunt. This technique utilizes flowing blood and quantifies platelet accumulation and fibrin deposition. However, the physical parameters of the thrombus have remained unknown. This study presents the development of a novel method to quantify the 3D physical properties of the thrombus on different biomaterials: expanded polytetrafluoroethylene and a preclinical hydrogel, poly(vinyl alcohol). Tubes of 4–5 mm inner diameter were exposed to non-anticoagulated blood flow for 1 hour and fixed. Due to differences in biomaterial water absorption properties, unique methods, requiring either the thrombus or the lumen to be radiopaque, were developed to quantify average thrombus volume within a graft. The samples were imaged using X-ray microcomputed tomography (microCT). The methodologies were strongly and significantly correlated to caliper-measured graft dimensions (R2 = 0.994, p < 0.0001). The physical characteristics of the thrombi were well correlated to platelet and fibrin deposition. MicroCT scanning and advanced image analyses were successfully applied to quantitatively measure 3D physical parameters of thrombi on cardiovascular biomaterials under flow.

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Reactive Ion Plasma Modification of Poly(Vinyl‐Alcohol) Increases Primary Endothelial Cell Affinity and Reduces Thrombogenicity

Cited by 16 publications

References 36 publications

Biomimetic modification of poly(vinyl alcohol): Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy

Biomimetic modification of poly(vinyl alcohol): Encouraging endothelialization and preventing thrombosis with antiplatelet monotherapy

Luminal Plasma Treatment for Small Diameter Polyvinyl Alcohol Tubular Scaffolds

Quantifying Physical Thrombus Characteristics on Cardiovascular Biomaterials Using MicroCT

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