In vitro blood compatibility of surface-modified polyurethanes

Bernacca, G M; Gulbransen, M.J.; Wilkinson, Ray; Wheatley, D. J.

doi:10.1016/s0142-9612(98)00016-7

Cited by 82 publications

(50 citation statements)

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“…[8][9][10] Polyurethane calcification is one of the major causes of device failure in experimental studies of polyurethane prosthetic heart valves, and ventricular assist systems. [11][12][13][14][15] Our polyurethane bisphosphonate derivatization studies demonstrated that covalent attachment of bisphosphonates effectively inhibited polyurethane mineralization, and had essentially no effect on the biomechanical properties of the polyurethane heart valve leaflets. 9,10,16 In the present studies, we utilized polyurethane films in order to investigate two unique surfaces for use in gene delivery studies: (1) Attaching a collagen coating to the surface of polyurethane films, with subsequent derivatization of the collagen coating with thiol-based attachment of anti-adenovirus antibodies, and (2) using alkyl-thiol-activated polyurethane films to directly attach anti-adenovirus antibodies to the surface of polyurethane surfaces.…”

Section: Introductionmentioning

confidence: 99%

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

et al. 2003

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The present study investigated a novel approach for gene therapy of heart valve disease and vascular disorders. We formulated and characterized implantable polyurethane films that could also function as gene delivery systems through the surface attachment of replication defective adenoviruses using an anti-adenovirus antibody tethering mechanism. Our hypothesis was that we could achieve site-specific gene delivery to cells interacting with these polyurethane implants, and thereby demonstrate the potential for intravascular devices that could also function as gene delivery platforms for therapeutic vectors. Previous research by our group has demonstrated that polyurethane elastomers can be derivatized post-polymerization through a series of chemical reactions activating the hard segment amide groups with alkyl bromine residues, which can enable a wide variety of subsequent chemical modifications. Furthermore, prior research by our group investigating gene delivery intravascular stents has shown that collagen-coated balloon expandable stents can be configured with anti-adenovirus antibodies via thiol-based chemistry, and can then tether adenoviral vectors at doses that lead to high levels of localized arterial neointima expression, but with virtually no distal spread of vector. Thus, we sought to create two-device configurations for our investigations building on this previous research. (1) Polyurethane films coated with Type I collagen were thiol activated to permit covalent attachment of anti-adenovirus antibodies to enable gene delivery via vector tethering. (2) We also formulated polyurethane films with direct covalent attachment of anti-adenovirus antibodies to polyurethane hard segments derivatized with alkyl-thiol groups, thereby also enabling tethering of replication-defective adenoviruses. Both formulations demonstrated highly localized and efficient transduction in cell culture studies with rat arterial smooth muscle cells. In vivo experiments with collagen-coated polyurethane films investigated an abdominal aorta implant model in pigs using a button configuration that simulated the blood contacting environment of a vascular graft. One week explants of the collagen-coated polyurethane films demonstrated 14.372.5% of neointimal cells on the surface of the implant transduced with green fluorescent protein -adenovirus (AdGFP) vector loadings of 1 Â 10 8 PFU. PCR studies demonstrated no detectable vector DNA in blood or distal organs. Similarly, polyurethane films with direct attachment of antivector antibodies to the surface were used in sheep pulmonary valve leaflet replacement studies, simulating the blood contacting environment of a prosthetic heart valve cusp. Polyurethane films with antibody tethered AdGFP vector (10 8 PFU) demonstrated 25.175.7% of attached cells transduced in these 1 week studies, with no detectable vector DNA in blood or distal organs. In vivo GFP expression was confirmed with immunohistochemistry. It is concluded that site-specific intravascular delivery of adenoviral vectors for g...

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Section: Introductionmentioning

confidence: 99%

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

et al. 2003

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“…Perhaps these findings are due to the fact that the results of the untreated P(3HB) are already within the range of the plasma-chemical modified PCL, which was observed in the literature [2], [14]. Furthermore, several interactions can occur between blood and foreign materials like the intrinsic coagulation pathway or the complement system [15]. Both pathways can also influence platelet activation and perhaps cause the higher β-thromboglobulin activity of untreated PCL compared to untreated P(3HB).…”

Section: Biocompatibilitymentioning

confidence: 85%

Surface functionalization of poly(ε-caprolactone) and poly(3-hydroxybutyrate) with VEGF

Teske¹,

Sternberg²

2017

BioNanoMaterials

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Abstract:In this study, surface modifications for the biodegradable polymers poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate) [P(3HB)] were developed in order to improve their suitability as scaffold material for bioartificial vessel prostheses. The challenge of wet-chemical surface modifications is to avoid bulk adjustments resulting in undesired changes in mechanical properties of these polymers. Nevertheless subsequent immobilization and controlled release of potent angiogenic biomolecules like vascular endothelial growth factor (VEGF) from the polymer surface is required. In order to improve the biocompatibility of PCL and P(3HB), terminal hydroxyl groups on the surface of these polymers were generated via oxygen (O 2 ) and carbon dioxide (CO 2 ) plasma. Then, the immobilization of VEGF was achieved through hydrolysable ester bonds using the crosslinker N,N′-disuccinimidyl carbonate (DSC). Our studies demonstrated that the plasma surface activations have no negative influence on the viability of L929 mouse fibroblasts and hemocompatibility. The immobilization of VEGF on the modified polymers via DSC is improved compared to the untreated reference. For the CO 2 plasma-chemical activated surfaces we observed the highest VEGF surface immobilization. Our release studies also reveal the highest cumulative release using CO 2 plasma-chemical activated samples.

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“…Polyurethanes have been extensively used in biomedical research [18] and offer excellent mechanical properties [11,12] and biocompatibility [15,[18][19][20][21]. Van Minnen et al [19] evaluated short-term (1, 4, 12 weeks) in vitro and in vivo biocompatibility aspects of a PU foam and found that the PU showed good in vitro and in vivo biocompatibility in these short-term experiments.…”

Section: Discussionmentioning

confidence: 99%

“…For example, this approach has proved highly successful for covalently attaching bisphosphonate groups at dosages sufficient to prevent PU heart valve leaflet calcification in both subdermal and circulatory implants [10][11][12]. PU calcification is one of the major causes of device failure in experimental studies of PU prosthetic heart valves, and ventricular assist systems [13][14][15][16]. Our PU bisphosphonate derivatization studies demonstrated that covalent attachment of bisphosphonates effectively inhibited PU mineralization, and had essentially no effect on the biomechanical properties of the PU heart valve leaflets [11,12].…”

Section: Introductionmentioning

confidence: 99%

Immobilization of gene vectors on polyurethane surfaces using a monoclonal antibody for localized gene delivery

Mei

Jin

Song

et al. 2006

The Journal of Gene Medicine

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In vitro blood compatibility of surface-modified polyurethanes

Cited by 82 publications

References 0 publications

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

Localized gene delivery using antibody tethered adenovirus from polyurethane heart valve cusps and intra-aortic implants

Surface functionalization of poly(ε-caprolactone) and poly(3-hydroxybutyrate) with VEGF

Immobilization of gene vectors on polyurethane surfaces using a monoclonal antibody for localized gene delivery

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