Biodegradable tissue composition with biodegradable cross-linkers

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 bioprosthesis comprising:
 an implantable tissue of biological origin that is decellularized and/or crosslinked, wherein the implantable tissue comprises a groove or hole, wherein said groove and/or said hole comprises a drug delivery composition having a drug; and   a coating coated on the biological implantable tissue, the coating having a composition selected from a group consisting of covalently crosslinked hydrogel and non-polymeric coating materials.   
     
     
         2 . The bioprosthesis of  claim 1 , wherein the hydrogel comprises polymers formed on the tissue by condensation polymerization. 
     
     
         3 . The bioprosthesis of  claim 1 , wherein the hydrogel is biodegradable. 
     
     
         4 . The bioprosthesis of  claim 1 , wherein the hydrogel is formed by crosslinking and polymerization of polyethylene glycol based water soluble macromonomers. 
     
     
         5 . The bioprosthesis of  claim 1 , wherein the tissue is fully coated with the coating. 
     
     
         6 . The bioprosthesis of  claim 1 , wherein the coating has a thickness of between about 5 micron to about 2 mm thick. 
     
     
         7 . The bioprosthesis of  claim 1 , wherein the tissue comprises bovine pericardium, porcine pericardium, equine pericardium, porcine submucosa, arterial tissue, vein tissue, corneal tissue, meniscus tissue, ligaments, bladder tissue, tendons, cartilage, heart valve tissue, demineralized bone, placenta, or umbilical cord tissue. 
     
     
         8 . The bioprosthesis of  claim 1 , further comprising the tissue having the drug therein for release after implantation. 
     
     
         9 . The bioprosthesis of  claim 1 , 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; wound healing agents; analgesics and analgesic combinations; local anesthetic agents; antihistamines; sedatives; angiogenesis-promoting agents; angiogenesis-inhibiting agents; and tranquilizers. 
     
     
         10 . The bioprosthesis of  claim 1 , wherein the drug delivery composition is liquid or solid, and the drug delivery composition comprises a bioerodable polymer or biodegradable polymer. 
     
     
         11 . The bioprosthesis of  claim 1  wherein the coating coats only a portion of the tissue. 
     
     
         12 . The bioprosthesis of  claim 1  wherein the coating is the non-polymeric material that is solid or liquid. 
     
     
         13 . The bioprosthesis of  claim 1  wherein the coating is the non-polymeric material that 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. 
     
     
         14 . The bioprosthesis of  claim 1 , wherein the biological implantable tissue is non-crosslinked and biodegradable. 
     
     
         15 . The bioprosthesis of  claim 1 , the coating comprising an enzyme that degrades tissue. 
     
     
         16 . The bioprosthesis of  claim 1 , the coating comprising a first layer having a drug and a second layer without the drug. 
     
     
         17 . The bioprosthesis of  claim 1 , the coating comprising a radiopaque material. 
     
     
         18 . The bioprosthesis of  claim 1  configured as a heart valve, vascular patch, vascular graft, tissue covered stent, stent graft, drug delivery patch, catheter, catheter part, strips, braided structure, weaved structure, ligament substitute, corneal implant, contact lens, intraocular lens, tissue scaffold, adhesive patch, meniscus implant, or bone implant. 
     
     
         19 . A bioprosthesis comprising:
 a biodegracable implantable tissue of biological origin that is decellularized and not crosslinked; and   a coating coated on the biological implantable tissue, the coating having a composition selected from a group consisting of covalently crosslinked hydrogel and non-polymeric coating materials.   
     
     
         20 . A bioprosthesis comprising:
 an implantable tissue of biological origin that is decellularized and/or crosslinked; and   a coating coated on the biological implantable tissue, the coating having a composition selected from a group consisting of covalently crosslinked hydrogel and non-polymeric coating materials, wherein the coating includes an enzyme that degrades tissue.