Abstract: Apparatus for sealing a puncture communicating with a blood vessel includes a porous carrier formed from lyophilized hydrogel or other material. The plug may include at least first and second hydrogel precursors and a pH adjusting agent carried by the porous carrier in an unreactive state prior to exposure to an aqueous physiological environment. Once exposed to bodily fluids, the carrier expands as the lyophilized material hydrates to enhance and facilitate rapid hemostasis of the puncture. When the plug is placed into the puncture, the natural wetting of the plug by bodily fluids (e.g., blood) causes the first and second precursors to react and cross-link into an adhesive or “sticky” hydrogel that aids in retaining the plug in place within the puncture.

Abstract: Pharmaceutically acceptable hydrogel polymers of natural, recombinant or synthetic origin, or hybrids thereof, are introduced in a dry, less hydrated, or substantially deswollen state and rehydrate in a physiological environment to undergo a volumetric expansion and to affect sealing, plugging, or augmentation of tissue, defects in tissue, or of organs. The hydrogel polymers may deliver therapeutic entities by controlled release at the site. Methods to form useful devices from such polymers, and to implant the devices are provided.

Abstract: An embodiment is a medical prosthesis for blocking or reducing tear flow through a punctum or canaliculus of a human eye and delivering a drug to the eye that comprises a dehydrated covalently crosslinked synthetic hydrophilic polymer hydrogel with dimensions to pass through a puncta lacrimali, with the dehydrated hydrogel absorbing physiological water to swell to at least 1 mm in cross-sectional width and conformably fit a canaliculus, with the hydrogel comprising a therapeutic agent dispersed through the hydrogel for release to an eye, with the hydrogel having a water content of at least about 50% by weight or volume when allowed to fully hydrate in vitro in physiological saline.

Abstract: Methods and apparatus of forming hydrogel systems in situ are provided using a delivery system configured to deliver two or more fluent prepolymer solutions without premature crosslinking. The delivery system comprises separate first and second lumens coupling first and second inlet ports and first and second outlet ports, respectively, and may include a balloon, flexible distal region, mixing chamber or steerable distal end. Multi-component hydrogel systems suitable for use with the inventive methods and apparatus are also described.

Abstract: Pharmaceutically acceptable hydrogel polymers of natural, recombinant or synthetic origin, or hybrids thereof, are introduced in a thy, less hydrated, or substantially deswollen state and rehydrate in a physiological environment to undergo a volumetric expansion and to affect sealing, plugging, or augmentation of tissue, defects in tissue, or of organs. The hydrogel polymers may deliver therapeutic entities by controlled release at the site. Methods to form useful devices from such polymers, and to implant the devices are provided.

Abstract: Pharmaceutically acceptable hydrogel polymers of natural, recombinant or synthetic origin, or hybrids thereof, are introduced in a dry, less hydrated, or substantially deswollen state and rehydrate in a physiological environment to undergo a volumetric expansion and to affect sealing, plugging, or augmentation of tissue, defects in tissue, or of organs. The hydrogel polymers may deliver therapeutic entities by controlled release at the site. Methods to form useful devices from such polymers, and to implant the devices are provided.

Abstract: Some aspects of this disclosure relate to a method for crosslinking a biological fluid comprising combining a biological fluid with a crosslinker to covalently crosslink proteins endogenous to the biological fluid to form a crosslinked gel. Examples of a biological fluid are blood, plasma, or serum.

Abstract: Some aspects of this disclosure relate to a method of treating an opthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel in situ at a peri-ocular, intra-ocular, or intra-vitreal site for controlled release of a therapeutic agent.

Abstract: Some aspects of this disclosure relate to a method for crosslinking a biological fluid comprising combining a biological fluid with a crosslinker to covalently crosslink proteins endogenous to the biological fluid to form a crosslinked gel. Examples of a biological fluid are blood, plasma, or serum.

Abstract: Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants. Visualization agents may be included with the crosslinked polymers.

Abstract: Certain embodiments include a surgical delivery system for a medical sealant including a packaging system with a detachable a sterile surface for mixing the sealant as needed for application.

Abstract: Some aspects of this disclosure relate to a method of treating an opthalmic disease affecting an eye of a patient comprising forming a covalently-crosslinked hydrogel in situ at a peri-ocular, intra-ocular, or intra-vitreal site for controlled release of a therapeutic agent.

Abstract: Compositions and methods are provided to control the release of relatively low molecular weight therapeutic species through hydrogels by first dispersing or dissolving such therapeutic species within relatively hydrophobic rate modifying agents to form a mixture. The mixture is formed into microparticles that are dispersed within bioabsorbable hydrogels, so as to release the water soluble therapeutic agents in a controlled fashion. Methods of using the compositions of the present invention in therapeutic systems 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: Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable, or not, are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants. Visualization agents may be included with the crosslinked polymers. Embodiments that include hydrogels having isolated hydrolytically degradable esters are set forth.

Abstract: Some aspects of the present disclosure relate to a surgical treatment for treating a tissue inside a vertebral column by forming a low-swelling biodegradable hydrogel in situ adherent to a tissue inside the vertebral column and substantially exterior to a theca in the vertebral column.

Abstract: Biocompatible crosslinked polymers, and methods for their preparation and use, are disclosed in which the biocompatible crosslinked polymers are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body. Applications for such biocompatible crosslinked polymers and their precursors include controlled delivery of drugs, prevention of post-operative adhesions, coating of medical devices such as vascular grafts, wound dressings and surgical sealants. Visualization agents may be included with the crosslinked polymers.

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: Compositions and methods are provided to control the release of relatively low molecular weight therapeutic species through hydrogels by first dispersing or dissolving such therapeutic species within relatively hydrophobic rate modifying agents to form a mixture. The mixture is formed into microparticles that are dispersed within bioabsorbable hydrogels, so as to release the water soluble therapeutic agents in a controlled fashion. Methods of using the compositions of the present invention in therapeutic systems are also provided.

Abstract: Methods and compositions for polymerizing materials with the process of making the material causing precipitation of an agent that is subsequently released by the material. In some aspects, controlled delivery of bioactive substances from biodegradable hydrogels is disclosed. In certain embodiments, biodegradable hydrogels formed in situ comprise entrapped precipitated proteins that are ordinarily water soluble. The dissolving and release of the bioactive substance is impeded by the hydrogel structure and takes place at a slow rate, thus controlling the release of said bioactive substance from the hydrogel. Thus a bioactive substance that would normally be rapidly dissolved in a physiological surrounding is, instead, released in a controlled manner. The hydrogel phase also serves to protect the bioactive agent from cells and enzymes present in physiological surroundings.