Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties

Alferiev, Ivan S.; Stachelek, Stanley J.; Lu, Zhibin; Fu, Angela L.; Sellaro, Tiffany L.; Connolly, Jeanne M.; Bianco, Richard W.; Sacks, Michael S.; Levy, Robert J.

doi:10.1002/jbm.a.10896

Cited by 41 publications

(34 citation statements)

References 35 publications

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“…[9][10][11]15,19 However, advances in the field have been confounded by the lack of reactive groups within the elastomer. Novel chemical syntheses developed by our group showed the feasibility of covalently …”

Section: Intravascular Adenovirus Implants Sj Stachelek Et Almentioning

confidence: 99%

“…[8][9][10] Initial studies showed that prosthetic heart valves composed of polyurethane with the anticalcification agent, bisphosphonate, covalently linked to the modified polyurethane surface was capable of resisting calcification beyond 5 months in an in vivo juvenile sheep model. [8][9][10] Although these first studies with modified polyurethane cardiovascular implants involved appending thiol-containing bisphosphonates in the form of a tetrabutylammonium salt, any thiol-containing moiety could theoretically be covalently attached to the bromoalkylated polyurethane surface. This makes feasible the use of polyurethane as a delivery platform for gene therapy vectors.…”

Section: Intravascular Adenovirus Implantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] For example, this approach has proved highly successful for covalently attaching bisphosphonate groups at dosages sufficient to prevent polyurethane heart valve leaflet calcification in both subdermal and circulatory implants. [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.…”

Section: Introductionmentioning

confidence: 99%

“…[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. These thiol-reactive sites were then further reacted in each instance to attach antiadenovirus antibodies for vector tethering.…”

Section: Introductionmentioning

confidence: 99%

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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: Intravascular Adenovirus Implants Sj Stachelek Et Almentioning

confidence: 99%

Section: Intravascular Adenovirus Implantsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2003

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Miscibility, crystallization kinetics, and mechanical properties of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)(PHBV)/poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate)(P3/4HB) blends

Wang

Chen

et al. 2010

J of Applied Polymer Sci

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Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)/poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) blend films were prepared by solvent-cast method. The nonisothermal crystallization results showed that PHBV and P3/4HB are miscible due to a single glass transition temperature (T g ), which is dependent on blend composition. The isothermal crystallization results demonstrate that the crystallization rate of PHBV becomes slower after adding amorphous P3/4HB with 19.2 mol% 4HB, which could be proved through depression of equilibrium melt point (T C and 84 C, respectively. FTIR analysis showed that PHBV/P3/4HB blend films would maintain the helical structure, similar to pure PHBV. Meanwhile, with increasing P3/4HB content, the inter-and intrainteractions of PHBV and P3/4HB decrease gradually. Besides, a lower elastic modulus and a higher elongation at break were obtained, which show that the addition of P3/ 4HB would make the brittle PHBV to ductile materials.

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Improved adhesion of silicone rubber to polyurethane by surface grafting

Wang

Xia

Liu

et al. 2011

J of Applied Polymer Sci

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Polyurethane (PU) has widespread applications in implantable devices because of its excellent mechanical and biocompatible properties, whereas weak biostability limits its long-term implantation. The introduction of silicone rubber (SR) onto the PU surface is an effective method for improving the biostability of PU, but the adhesion of these two polymers is unsatisfactory. In this study, the surface modification of PU via grafting through the introduction of vinyl and SiAH groups onto the PU surface was attempted to improve the adhesion of PU to SR. Fourier transform infrared, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy were employed to investigate the graft reaction on the PU surface.The interfacial and surface morphology was characterized with scanning electron microscopy. Different PU/SR interfaces after oscillation and shear were compared as well. The results indicated that the PU surface was activated by diisocyanate, which generated free isocyanate groups for the further grafting of vinyl and SiAH groups. When additiontype, room-temperature-vulcanized SR was poured onto the PU surface, the vinyl and SiAH groups on the PU surface underwent an addition reaction, which improved the adhesion of PU and SR by connecting them with chemical bonds.

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Prevention of polyurethane valve cusp calcification with covalently attached bisphosphonate diethylamino moieties

Abstract: DBP polyurethane possesses physical (water absorption) and biomechanical properties comparable to unmodified polyurethane and can resist intrinsic heart-valve leaflet calcification in blood-stream implants.

Cited by 41 publications

References 35 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

Miscibility, crystallization kinetics, and mechanical properties of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)(PHBV)/poly(3‐hydroxybutyrate‐co‐4‐hydroxybutyrate)(P3/4HB) blends

Improved adhesion of silicone rubber to polyurethane by surface grafting

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