Abstract: Oxidation resistant bioprosthetic tissues and oxidation resistant bioprosthetic heart valve leaflets are described. Also provided are methods for preparing the oxidation resistant bioprosthetic tissues and bioprosthetic heart valve leaflets, and methods for preventing oxidative degeneration in bioprosthetic tissues, including immobilizing covalently an effective amount of an antioxidant to the bioprosthetic tissue.

Abstract: A water-soluble photo-activatable polymer including: a photo-activatable group adapted to be activated by an irradiation source and to form a covalent bond between the water-soluble photo-activatable polymer and a matrix having at least one carbon; a reactive group adapted to covalently react with a biomaterial for subsequent delivery of the biomaterial to a cell; a hydrophilic group; and a polymer precursor. A composition including a monomolecular layer of the water-soluble photo-activatable polymer and a matrix having at least one carbon, wherein the monomolecular layer is covalently attached to the matrix by a covalent bond between the photo-activatable group and the at least one carbon. The composition further includes a biomaterial having a plurality of active groups, wherein the biomaterial is covalently attached to the monomolecular layer by covalent bonding between the active groups and reactive groups. Also provided is a method for delivery of a biomaterial to a cell.

Abstract: The present invention relates to methods for treating or preventing a mitral valve disease in a subject in need thereof, comprising administering to the subject an effective amount of a therapeutic agent. The therapeutic agent is capable of suppressing serotonin receptor signaling. The methods may be combined with a mitral valve surgery, serotonin transporter polymorphism genotyping, MV disease diagnosis, and/or an adjunct assay. Also provided are related medicaments, pharmaceutical compositions, and methods for preparing the medicaments.

Abstract: An apparatus for preloading magnetic particles or cells onto a medical device includes a device carrier and a particle carrier attached over the device carrier. At least one magnet is inserted into the device carrier, the at least one magnet extending inside a section of the device carrier, over which the particle carrier is attached, to attract magnetic particles or cells to the particle carrier when the apparatus is placed in a suspension of magnetic particles or cells. A method for preloading magnetic particles or cells onto a medical device includes attaching one or more magnets to a device carrier, attaching a particle carrier to the device carrier in proximity to the one or more magnets, and inserting the device carrier with the attached particle carrier and the one or more magnets into a suspension containing magnetic particles or cells to preload the particle carrier with magnetic particles or cells.

Abstract: A therapeutic particle comprises a particle comprising one or more therapeutic agents and one or more fibrin-avid peptide variants attached to the surface of the particle. A method for magnetically targeting a therapeutic agent toward a device in a subject, such as a temporarily introduced magnetizable catheter or an implanted stent, comprises administering the therapeutic particles to the subject and generating a magnetic field, which targets the magnetic particles toward the device. The affinity peptide-modified therapeutic particles may comprise an effective amount of an anti-proliferative agent, such as paclitaxel, to inhibit or prevent in-stent restenosis.

Abstract: A prodrug according to formula (I) wherein R2 is a residue of a drug, said drug having a hydroxyl group by which the COOR2 group is formed; Z is O or NH; m is 0 or 1; and R3 is an organic moiety comprising a lipophilic group or a residue of a polymer, provided that Z is 0 if the polymer is carboxymethyl dextran. A system includes a plurality of magnetic nanoparticles including a prodrug as described above, a stent and a source of uniform magnetic field capable of producing temporary magnetization of the stent and/or the magnetic nanoparticles. A method of treating a medical condition with a drug includes administering to a patient in need of the drug a prodrug as described above, the prodrug being capable of releasing the drug in the patient after the administration step.

Abstract: The present invention relates to a hybrid graft and methods of generating the hybrid graft. The hybrid graft comprises an exterior surface and a luminal surface. The luminal surface comprises a micropattern of grooves to which cells adhere and orient along. The exterior surface comprises electrospun microfibers wherein the microfibers provide mechanical properties to the graft. The hybrid graft is capable supporting endothelial cell attachment, endothelial cell alignment, cell proliferation, and maintaining their in vivo function. The graft of the invention can recapitulate the in vivo morphology and function of natural vascular endothelium.

Abstract: Methods for protecting biomaterials comprise attaching CD47 or Ig domain thereof to the surface of the biomaterial, thereby inhibiting or reducing immune cell attachment and/or immune cell-mediated damage to the biomaterial. Also provided are kits for practicing these methods and the protected biomaterials.

Abstract: A therapeutic particle comprises a particle comprising one or more therapeutic agents and one or more fibrin-avid peptide variants attached to the surface of the particle. A method for magnetically targeting a therapeutic agent toward a device in a subject, such as a temporarily introduced magnetizable catheter or an implanted stent, comprises administering the therapeutic particles to the subject and generating a magnetic field, which targets the magnetic particles toward the device. The affinity peptide-modified therapeutic particles may comprise an effective amount of an anti-proliferative agent, such as paclitaxel, to inhibit or prevent in-stent restenosis.

Abstract: The present invention relates to a hybrid graft and methods of generating the hybrid graft. The hybrid graft comprises an exterior surface and a luminal surface. The luminal surface comprises a micropattern of grooves to which cells adhere and orient along. The exterior surface comprises electrospun microfibers wherein the microfibers provide mechanical properties to the graft. The hybrid graft is capable supporting endothelial cell attachment, endothelial cell alignment, cell proliferation, and maintaining their in vivo function. The graft of the invention can recapitulate the in vivo morphology and function of natural vascular endothelium.

Abstract: Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Also provided are bioresorbable nanoparticles prepared without the use of organic solvents, and methods for therapeutically using such bioresorbable nanoparticles.

Abstract: A treatment system includes a magnetic targeting catheter and a plurality of MNP. The MNP may include one or more magnetic field-responsive agents and one or more therapeutic agents. The catheter may include an inner shaft having at least one lumen and a fluid delivery balloon adapted to administer a fluid from the inner shaft into a space surrounding the catheter. An expandable mesh formed of a magnetizable material may surround the fluid delivery balloon. The catheter may further include one or more occlusion balloons for controlling blood flow through a vessel in which the catheter is placed. A method of treating a medical condition may include advancing a magnetic targeting catheter to a site, deploying an expandable mesh connected to the catheter, applying a magnetic field to the mesh and depositing a plurality of MNP or cells loaded with MNP near the mesh.

Abstract: Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Therapeutic particles can comprise antioxidant enzymes, and can be targeted to cells to protect the cells from oxidative damage.

Abstract: An ester of ArOH according to the formula R—X—CO—OAr, wherein ArOH is a pharmaceutically active compound selected from the group consisting of SN-38, PI-103, etoposide and fenretinide, wherein a) R is a residue of cholesterol, sitosterol, SN-38, PI-103, etoposide or fenretinide and X is O—CO-L, wherein L is either a direct bond or a linking group including a branched or unbranched hydrocarbyl moiety that may optionally include in-chain or pendant heteroatom substituents and/or cyclic moieties; b) R—X—CO-0 is an all-trans retinoate radical or the 9-cis or 13-cis isomer thereof; or c) R—X— is a branched or unbranched, saturated or unsaturated hydrocarbyl moiety comprising at least 5 carbon atoms and optionally including at least one in-chain or pendant heteroatom substituent and/or cyclic moiety.

Abstract: Methods for inhibiting a biomaterial-associated thrombotic event comprise reducing the number of platelets that bind to the biomaterial, or inhibiting platelet activation, by attaching CD47 or the Ig domain thereof to the surface of the biomaterial. Methods of the present invention inhibit thrombi formation on or near a biomaterial that is on the surface of an implant, medical device, tube, or therapeutic delivery vehicle. Also provided are kits for practicing these methods and the modified biomaterials.

Abstract: Oxidation resistant bioprosthetic tissues and oxidation resistant bioprosthetic heart valve leaflets are described. Also provided are methods for preparing the oxidation resistant bioprosthetic tissues and bioprosthetic heart valve leaflets, and methods for preventing oxidative degeneration in bioprosthetic tissues, including immobilizing covalently an effective amount of an antioxidant to the bioprosthetic tissue.

Abstract: Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Also provided are bioresorbable nanoparticles prepared without the use of organic solvents, and methods for therapeutically using such bioresorbable nanoparticles.

Abstract: A polymer is provided according to structure I wherein Y is a thiol-reactive group and Z is an ionogenic group. The surface of a polymeric substrate is modified by contacting the surface with a polymer according to structure II or structure III and exposing the surface to ultraviolet light, optionally followed by contacting the modified surface with the polymer according to structure I.

Abstract: A method and a composition for delivery of a biomaterial to an animal cell or a tissue, the composition includes (a) a biomaterial; (b) a biodegradable cross-linker portion having a hydrolyzable bond, wherein the biodegradable cross-linker portion is covalently bound to the biomaterial; and (c) a substrate, wherein the substrate is covalently bound to the biodegradable cross-linker portion, provided that the biodegradable cross-linker is adapted to hydrolyze by breaking the hydrolyzable bond and thereby release and deliver the biomaterial. A process of making the composition is also provided.

Abstract: A prodrug according to formula (I) wherein R2 is a residue of a drug, said drug having a hydroxyl group by which the COOR2 group is formed; Z is O or NH; m is 0 or 1; and R3 is an organic moiety comprising a lipophilic group or a residue of a polymer, provided that Z is 0 if the polymer is carboxymethyl dextran. A system includes a plurality of magnetic nanoparticles including a prodrug as described above, a stent and a source of uniform magnetic field capable of producing temporary magnetization of the stent and/or the magnetic nanoparticles. A method of treating a medical condition with a drug includes administering to a patient in need of the drug a prodrug as described above, the prodrug being capable of releasing the drug in the patient after the administration step.