Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules. A medical condition at a localized site is treated by applying a polymerization initiator and then applying a substantially water-soluble, degradable macromer of at least 200 mw and having at least two crosslinkable substituents, and polymerizing the macromer to form a crosslinked polymeric material at the site.

Abstract: Herein is disclosed a method of cross-linking a tissue, comprising treating the tissue under effective cross-linking conditions with a diunsaturated organic compound comprising structure I: 1

Abstract: Methods and compositions are provided for preparing protein concentrates from protein comprising aqueous compositions. In the subject methods, an initial protein comprising aqueous compositions, such as whole blood or a derivative thereof, is contacted with a non-protein denaturant hydrogel under conditions sufficient for a substantial amount of water present in the composition to be absorbed by the hydrogel, resulting in the production of a protein concentrate, such as a fibrinogen rich composition. Of particularl interest is the use of the subject methods to prepare fibrinogen rich compositions, where such compositions produced according to the subject invention are useful in fibrin sealants, drug delivery vehicles and in a number of other diverse applications.

Abstract: A method of cross-linking a tissue, comprising treating the tissue under effective cross-linking conditions with a fluid comprising a compound comprising P(CH2OH)3Xn, wherein X is selected from C1-C10 carboxyl, sulfonic acid, sulfonic acid salts, C1-C10 alcohol, or halogens, and n is an integer from 0 to 2, inclusive, and all —X and —CH2OH groups are bonded to the phosphorus atom. In one embodiment, the compound is &bgr;-(tris(hydroxymethyl)phosphino)proprionic acid (THPP).

Abstract: Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Abstract: Gel-forming macromers including at least four polymeric blocks, at least two of which are hydrophobic and at least one of which is hydrophilic, and including a crosslinkable group are provided. The macromers can be covalently crosslinked to form a gel on a tissue surface in vivo. The gels formed from the macromers have a combination of properties including thermosensitivity and lipophilicity, and are useful in a variety of medical applications including drug delivery and tissue coating.

Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a “glue” to cause more than one biological substance to adhere together, or as carriers for biologically active species.

Abstract: An impoved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, tissue is stained with a photoinitiator, then the polymer solution or gel having added thereto a defined amount of the same or a different photoinitiator is applied to the tissue. On exposure to light, the resulting system polymerizes at the surface, giving excellent adherence, and also forms a gel in the rest of the applied volume. Thus a gel barrier of arbitrary thickness can be applied to a surface while maintaining high adherence at the interface. This process is referred to herein as “priming”. The polymerizable barrier materials are highly useful for sealing tissue surfaces and junctions against leaks of fluids. In another embodiment, “priming” can be used to reliably adhere preformed barriers to tissue or other surfaces, or to adhere tissue surfaces to each other.

Abstract: A method for treating biological tissue is provided in which a cross-linked biological tissue containing free aldehyde groups is reacted with a suitable neutralization agent in order to chemically block the aldehyde groups from reactivity toward cellular proteins. Also provided is the cross-linked biological tissue so produced which is substantially free of reactive aldehyde groups and, as a result, exhibits reduced toxicity and improved biocompatibility.

Abstract: Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Abstract: A method for alleviating the symptoms of a cosmetic or dermatologic skin condition is described. An effective amount of a poly(hydroxy acid)/polymer conjugate in a pharmaceutically or cosmetically acceptable vehicle is provided. Topical compositions of the conjugates with another cosmetic or dermatological agent, and compounds of the conjugates having attached physiologically active functional groups, are also provided.

Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a “glue” to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization.

Abstract: Gel-forming macromers including at least four polymeric blocks, at least two of which are hydrophobic and at least one of which is hydrophilic, and including a crosslinkable group are provided. The macromers can be covalently crosslinked to form a gel on a tissue surface in vivo. The gels formed from the macromers have a combination of properties including thermosensitivity and lipophilicity, and are useful in a variety of medical applications including drug delivery and tissue coating.

Abstract: A method for cross-linking biological tissue is provided which uses as a cross-linking agent a low molecular weight, substantially monomeric polyfunctional aldehyde formed in situ or just prior to cross-linking. The polyfunctional aldehyde is essentially free of the undesirable heterogeneous polymeric species that result from polyfunctional aldehyde self-reactivity. Also provided is biological tissue that is cross-linked with a substantially monomeric glutaraldehyde.

Abstract: A method and apparatus for molding polymeric structures in vivo is disclosed. The structures comprise polymers that may be heated to their molding temperature by absorption of visible or near-visible wavelengths of light. By providing a light source that produces radiation of the wavelength absorbed by the polymeric material, the material may be selectively heated and shaped in vivo without a corresponding heating of adjacent tissues or fluids to unacceptable levels. The apparatus comprises a catheter having a shaping element positioned near its distal end. An emitter provided with light from at least one optical fiber is positioned within the shaping element. The emitter serves to provide a moldable polymeric article positioned on the shaping element with a substantially uniform light field, thereby allowing the article to be heated and molded at a desired treatment site in a body lumen.

Abstract: Collagen-containing tissue is cross-linked to provide tissue suitable for use in production of bioprosthetic devices. A cross-linking agent is used having an aliphatic component containing about 8 to 40 carbon atoms and two collagen-reactive groups such as isocyanate, epoxy or n-hydroxysuccinimide. The cross-linking agent may be produced by dimerizing fatty acids, and modifying carboxylic acid group of the fatty acids before or after dimerization to contain collagen-reactive groups. The cross-linked tissue has desirable mechanical and biocompatibility features and a reduced susceptibility to calcification.

Abstract: The disclosed invention relates to the process of fixating tissue to obtain tissue for bioprosthetic applications. The fixating process comprises exposing the tissue to a fluid comprising activated difunctional or polyfunctional acids that can react with amino groups in tissue under mild conditions. Activating moieties include disuccinimidyl moieties, n-hydroxy disuccinimidyl moieties, sulfo-disuccinimidyl moieties, and mixtures thereof. The acid is preferably aliphatic difunctional or polyfunctional acids, more preferably a naturally occurring aliphatic difunctional or polyfunctional acids. Even more preferred is an acid consisting of glutaric, suberic acid, sebacic acid, tartaric acid, or mixtures thereof. The activated difunctional or polyfunctional acids are esters comprising the difunctional or polyfunctional acids and the activating moieties.

Abstract: An impoved barrier or drug delivery system which is highly adherent to the surface to which it is applied is disclosed, along with methods for making the barrier. In the preferred embodiment, tissue is stained with a photoinitiator, then the polymer solution or gel having added thereto a defined amount of the same or a different photoinitiator is applied to the tissue. On exposure to light, the resulting system polymerizes at the surface, giving excellent adherence, and also forms a gel in the rest of the applied volume. Thus a gel barrier of arbitrary thickness can be applied to a surface while maintaining high adherence at the interface. This process is referred to herein as "priming". the polymerizable barrier materials are highly useful for sealing tissue surfaces and junctions against leaks of fluids. In another embodiment, "priming" can be used to reliably adhere preformed barriers to tissue or other surfaces, or to adhere tissue surfaces to each other.

Abstract: Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.

Abstract: Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.