Implantable tissue compositions and method

Abstract

Novel implantable tissue fixation methods and compositions are disclosed. Methods and compositions of tissue, fixed using polymeric and/or variable length crosslinks, and di- or polymercapto compounds are described. Also described are the methods and compositions wherein the tissue is fixed using biodegradable crosslinkers. Methods and compositions for making radio-opaque tissue are also described. Methods and compositions to obtain a degradable implantable tissue-synthetic biodegradable polymer composite are also described. Compositions and methods of incorporating substantially water-insoluble bioactive compounds in the implantable tissue are also disclosed. The use of membrane-like implantable tissue to make an implantable drug delivery patch are also disclosed. Also described are the compositions and methods to obtain a coated implantable tissue. Medical applications implantable tissue such as heart valve bioprosthesis, vascular grafts, meniscus implant, drug delivery patch are also disclosed.

1 . A bioprosthetic article comprising an implantable tissue coated with a composition selected from a group consisting of covalently crosslinked hydrogel and non-polymeric coating materials. 
     
     
         2 . The article of  claim 1  wherein the implantable tissue, before coating, is chosen from the group consisting of decellularized tissue, chemically modified tissue, and crosslinked tissue. 
     
     
         3 . The article of  claim 2  wherein the crosslinked tissue is obtained by a process chosen from the group consisting of glutaraldehyde crosslinking, ethyl-3-(3-dimethylaminopropyl carbodiimide (EDC) crosslinking, dye mediated photooxidation crosslinking, and hexamethylene diisocyanate crosslinking. 
     
     
         4 . The article of  claim 1  wherein the hydrogel comprises polymers formed on the tissue by condensation polymerization. 
     
     
         5 . The article of  claim 1  wherein the hydrogel comprises a reaction product of reactive precursor species that comprise nucleophilic functional groups and reactive precursor species that comprise electrophilic functional groups. 
     
     
         6 . The article of  claim 1  wherein the hydrogel comprises polymers formed on the tissue by free radical polymerization. 
     
     
         7 . The article of  claim 6  wherein the hydrogel comprises a polymer polymerized from a monomer chosen from the group consisting of acrylates, methacrylates, acrylamides, methacrylamide vinyl ethers, and n-vinyl pyrrolidinone. 
     
     
         8 . The article of  claim 1  wherein the hydrogel is biodegradable. 
     
     
         9 . The article of  claim 8  wherein the hydrogel comprises a polymer polymerized from a monomer chosen from the group consisting of lactide, glycolide, and caprolactone. 
     
     
         10 . The article of  claim 1  wherein the hydrogel is formed by crosslinking and polymerization of polyethylene glycol based water soluble macromonomers. 
     
     
         11 . The article of  claim 1  wherein the tissue is has two opposing sides joined by a thickness, with the coating being on each of the two opposing sides. 
     
     
         12 . The article of  claim 1  wherein the coating has a thickness of between about 5 micron to about 2 nm thick. 
     
     
         13 . The article of  claim 1  wherein the tissue comprises bovine pericardium, porcine pericardium, equine pericardium, porcine submucosa arterial tissue, vein tissue, ureter tissue, corneal tissue, an aortic root, meniscus tissue, ligaments, basal membrane, bladder tissue, tendons, cartilage, heart valve tissue, demineralized bone, placenta, umbilical cord tissue, skin tissue, cadaver tissue, and dura mater. 
     
     
         14 . The article of  claim 1  further comprising a drug for release after implantation. 
     
     
         15 . The article of  claim 14  wherein a drug is selected from the group consisting of antiviral agents; antiinfectives, antibiotics; antipruritics; antipsychotics; cholesterol- or lipid-reducing agents; cell cycle inhibitors; anticancer agents; antiparkinsonism drugs; HMG-CoA inhibitors; antirestenosis agents; antiinflammatory agents; antiasthmatic agents; anthelmintic; immunosuppressives; muscle relaxants; antidiuretic agents; vasodilators; nitric oxide; nitric oxide-releasing compounds; beta-blockers; hormones; antidepressants; decongestants; calcium channel blockers; growth factors, bone growth factors, bone morphogenic proteins; wound healing agents; analgesics and analgesic combinations; local anesthetic agents; antihistamines; sedatives; angiogenesis-promoting agents; angiogenesis-inhibiting agents; and tranquilizers. 
     
     
         16 . The article of  claim 1  wherein the tissue comprises a groove or hole, wherein said groove and/or said hole comprises a drug delivery composition. 
     
     
         17 . The article of  claim 16  wherein the drug delivery composition comprises a member chosen from the group consisting of a bioerodible polymer, a biodegradable polymer, a solid drug matrix, and a liquid drug. 
     
     
         18 . The article of  claim 1  wherein the coating coats only a portion of the tissue. 
     
     
         19 . A process of preparing a bioprosthetic article comprising applying monomers or polymers to a surface of an implantable tissue and reacting the monomers or polymers on the surface to form a hydrogel. 
     
     
         20 . The process of  claim 19  wherein the implantable tissue, before coating, is chosen from the group consisting of decellularized tissue, chemically modified tissue and crosslinked tissue. 
     
     
         21 . The process of  claim 19  wherein the reaction comprises condensation polymerization of the polymers. 
     
     
         22 . The process of  claim 19  wherein the reaction comprises free radical polymerization of the monomers. 
     
     
         23 . The process of  claim 19  wherein the hydrogel is biodegradable. 
     
     
         24 . The process of  claim 19  wherein the hydrogel is formed by crosslinking and polymerization of polyethylene glycol based water soluble macromonomers. 
     
     
         25 . The article of  claim 1  wherein the non-polymeric material is solid or liquid. 
     
     
         26 . The article of  claim 1  wherein the non-polymeric material is selected from the group consisting of bone wax, fatty acids, stearic acid. oleic acid, sugar derivatives, sucrose acetate, mineral oil, peanut oil, cotton seed oil, tocopherol, vitamin E, vitamin E acetate and polyethylene glycol. 
     
     
         27 . A method of treating a patient comprising applying the bioprosthetic article of  claim 1  to the patient for post operative adhesion prevention or as a hernia patch.