Multi-layered surgical prosthesis

Abstract

The invention relates to prostheses having a multi-layered sheet structure comprising at least two continuous polymer film layers. Also disclosed are methods of manufacturing the prostheses, as well as methods of treating a patient by implanting them into a patient. The prostheses are used in hernia repair, the repair of anatomical defects of the abdominal wall, diaphragm and chest wall, correction of defects in- the genitourinary system, and repair of traumatically damaged organs such as the spleen, liver or kidney.

1 . A prosthesis having a multi-layered sheet structure comprising at least two continuous polymer film layers, wherein the at least two continuous polymer film layers are integrally formed with no distinguished filaments or fibers within each layer, wherein the at least two continuous polymer film layers are in continuous contact with each other to form the multi-layered sheet structure. 
     
     
         2 . The prosthesis according to  claim 1 , wherein at least one layer of the multi-layered structure is a porous layer having pores. 
     
     
         3 . The prosthesis according to  claim 2 , wherein the pores extend from one surface of the porous layer to the second surface of the porous layer to form through-holes in the porous layer. 
     
     
         4 . The prosthesis according to  claim 2 , wherein the pores extend from one surface of the prosthesis to the other surface of the prosthesis to form through-holes in the multi-layered structure of the prosthesis. 
     
     
         5 . The prosthesis according to  claim 2 , wherein the porous layer has a high friction to enable a good anchoring to abdominal tissues. 
     
     
         6 . The prosthesis according to  claim 2 , wherein the porous layer has a high wetting ability to enable anchoring to abdominal tissues. 
     
     
         7 . The prosthesis according to  claim 2 , wherein the surface opposite to the surface of the porous layer has an anti-adhesion effect for visceral tissue. 
     
     
         8 . The prosthesis according to  claim 1 , additionally comprising an anti-adhesion coating layer on at least a part of one or both outer surface(s) of the prosthesis. 
     
     
         9 . The prosthesis according to  claim 8 , wherein the anti-adhesion coating layer comprises a biocompatible or bioresorbable polymer. 
     
     
         10 . The prosthesis according to  claim 8 , wherein the anti-adhesion coating layer comprises an anti-adhesion agent. 
     
     
         11 . The prosthesis according to  claim 10 , wherein the anti-adhesion agent is a carboxymethyl cellulose, collagen, omega-3 fatty acid, hyaluronic acid, oxidized regenerated cellulose, gelatin, polysaccharides, biocompatible surfactants like polyethylene glycols, polypropylene glycols or poloxamers, and derivatives and/or blends from these materials. 
     
     
         12 . The prosthesis according to  claim 1 , wherein each of the layers of the multi-layered structure comprises a biocompatible or bioresorbable polymer material. 
     
     
         13 . The prosthesis according to  claim 9 , wherein the biocompatible polymer material is any of polyvinylidene fluoride, polyamide, polyethylene, polypropylene, poly(ethylene terephtalate), polyurethane, polystyrene, polymethacrylate, polytetrafluoroethylene, and polymers or copolymers of p-dioxanone, trimethylene carbonate (1,3-dioxan-2-one) and alkyl derivatives thereof, valerolactone, butyrolactone, decalactone, hydroxybutyrate, hydroxyvalerate, 1,5-dioxepan-2-one, 1,4-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one or any polymer blend thereof. 
     
     
         14 . The prosthesis according to  claim 9 , wherein the bioresorbable polymer material is any of polyglycolide, polylactide and poly-co-glycolactide, polylactic acid, polyglycolic acid, poly(ethylene glycolide), polyethylene glycol, polycaprolactone like poly(ε-caprolactone), polydioxanone, polygluconate, polylactic acid-polyethylene oxide copolymers, polysaccharides, cellulose derivatives, hyaluronic acid based polymers, starch, gelatin, collagen, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(amino acids) or any polymer blends, copolymers, or derivatives thereof. 
     
     
         15 . The prosthesis according to  claim 2 , wherein the pores have an average pore size of about 0.5-5 mm. 
     
     
         16 . The prosthesis according to  claim 2  wherein the pores have an average pore size of about 1-4 mm. 
     
     
         17 . The prosthesis according to  claim 2 , wherein the pores have a regular or irregular shape. 
     
     
         18 . The prosthesis according to  claim 17 , wherein the pores having a regular shape have a circular, elliptical, oval or polygonal shape such as a triangular, square, pentagonal or rhomb-like shape. 
     
     
         19 . The prosthesis according to  claim 17 , wherein the pores having an irregular shape have a non-circular cross-section or a monosymmetric shape to provide an anisotropic pore structure. 
     
     
         20 . The prosthesis according to  claim 17 , wherein coplanar pores in the multi-layered structure have different pore diameters or pore shapes to provide an anisotropic pore structure. 
     
     
         21 . The prosthesis according to  claim 2 , wherein the pores have an anisotropic shape in its cross-section. 
     
     
         22 . The prosthesis according to  claim 21 , wherein the anisotropic shape of the pores tapers from the upper surface of the porous layer to the inner part thereof or the opposite side of the prosthesis. 
     
     
         23 . The prosthesis according to  claim 19 , wherein the anisotropic pore structure or the anisotropic shape of the pores is adapted to the anisotropic anatomical nature of a site at which the prosthesis is to be inserted in a patient. 
     
     
         24 . The prosthesis according to  claim 1 , wherein one, two, or more of the layers of the multi-layered structure like the porous layer or the anti-adhesion coating layer are drug-releasing layers comprising one or more releasable drugs, therapeutic agents and/or pharmaceutically active substances. 
     
     
         25 . The prosthesis according to  claim 1 , further comprising an additional polymeric drug-releasing layer on one or both outermost layers of the prosthesis, comprising one or more releasable drugs, therapeutic agents and/or pharmaceutically active substances. 
     
     
         26 . The prosthesis according to  claim 24 , wherein the drug is selected from the group consisting of a small chemical molecule, a peptide, a protein a nucleic acid or any combination thereof. 
     
     
         27 . The prosthesis according to  claim 26 , wherein the protein is selected from an antibody or antibody binding fragment thereof, a growth factor such as an anti-microbial growth factor, and/or a cardiovascular therapeutic protein. 
     
     
         28 . The prosthesis according to  claim 26  wherein the small chemical molecule is selected from an anti-inflammatory agent, an analgetic agent, an anti-microbial agent, a wound-healing or scar formation preventing agent, and/or an anti-restenotic or immunodepressive agent. 
     
     
         29 . The prosthesis according to  claim 1 , wherein the prosthesis has memory effect properties. 
     
     
         30 . The prosthesis according to  claim 29  comprising two additional layers providing the memory effect properties in its multi-layered sheet structure. 
     
     
         31 . The prosthesis according to  claim 1 , wherein the multi-layered sheet structure is substantially flexible along the longitudinal axis of the sheet structure. 
     
     
         32 . The prosthesis according to  claim 1 , wherein the multi-layered sheet structure comprises at least two different pore structures wherein the first pore structure comprises through holes through the porous layer or through the prosthesis and the second pores structure comprises one or more wells or pot holes on those parts of the porous layer where the first pore structure is not provided, wherein the depth of the wells or pot holes is smaller as the thickness of the porous layer. 
     
     
         33 . A method of manufacturing a prosthesis having a multi-layered sheet structure, comprising integrally forming at least two continuous polymer film layers with no distinguished filaments or fibers within each layer, wherein the at least two continuous polymer film layers are in continuous contact with each other to produce the multi-layered sheet structure. 
     
     
         34 . The method according to  claim 33 , wherein the at least two layers are formed by molding methods like injection molding and compression molding; coating methods like dip coating or spin coating; solution casting; and/or an extrusion method like blow extrusion or film extrusion. 
     
     
         35 . The method according to  33 , wherein the outermost layer of the multi-layered sheet structure is formed by casting the polymer on a roughened mold to obtain a roughed surface, forming the additional layers thereon and, then, mechanically or chemically treating said roughed surface of the porous layer to increase its surface friction and wetting ability. 
     
     
         36 . The method according to  claim 35 , wherein the mechanical treatment of the roughed surface includes a plasma treatment, a sandblasting treatment, an embossing treatment, or a sizing treatment. 
     
     
         37 . The method according to  claim 35 , wherein the chemical treatment of the roughed surface comprises an etching treatment or a coating like a plasma polymerization coating or solution coating. 
     
     
         38 . The method according to  claim 33 , wherein the outermost layer of the multi-layered structure is made by dispersing inorganic or organic fine particles and/or inorganic/organic composite particles in the polymer mixture and then molding the respective layer to obtain a roughened surface. 
     
     
         39 . The method according to  claim 38 , wherein the inorganic particles include silica, titania, bentonite, clays or mixtures thereof. 
     
     
         40 . The method according to  claim 38 , wherein the organic particles include oligomers or polymers having a melting point higher than the polymer of the polymeric film. 
     
     
         41 . The method according to  claim 38 , wherein the inorganic/organic composite particles include particles of silica or titania in the core and a polymeric shell. 
     
     
         42 . The method according to  claim 33 , wherein pores are made in one or more layers of the multi-layered structure by using a matrix having a pore pattern. 
     
     
         43 . The method according to  claim 33 , wherein a porous layer is formed in the form of a solid layer as an outermost layer and then the porous structure is formed from this solid layer by means of a mechanical treatment. 
     
     
         44 . The method of  claim 43 , wherein the mechanical treatment is a grinding process, a laser cutting process, an electrical discharge machining, stamping or a mechanical abrading process. 
     
     
         45 . The method according to  claim 33 , wherein an anti-adhesion coating layer is formed on at least a part of one or both outer surface(s) of the prosthesis. 
     
     
         46 . The method according to  claim 45 , wherein the anti-adhesion coating layer comprises a biocompatible or bioresorbable polymer. 
     
     
         47 . The method according to  claim 45 , wherein the anti-adhesion coating layer comprises an anti-adhesion agent. 
     
     
         48 . The method according to  claim 33 , wherein the multi-layered structure is made of at least two layers comprising a biocompatible or bioresorbable polymer material. 
     
     
         49 . The method according to  claim 46 , wherein the biocompatible polymer material is any of polyvinylidene fluoride, polyamide, polyethylene, polypropylene, poly(ethylene terephtalate), polyurethane, polystyrene, polymethacrylate, polytetrafluoroethylene, and polymers or copolymers of p-dioxanone, trimethylene carbonate and alkyl derivatives thereof, valerolactone, butyrolactone, decalactone, hydroxybutyrate, hydroxyvalerate, 1,5-dioxepan-2-one, 1,4-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one or any polymer blend thereof. 
     
     
         50 . The method according to  claim 46 , wherein the bioresorbable polymer material is any of polyglycolide, polylactide and poly-co-glycolactide, polylactic acid, polyglycolic acid, poly(ethylene glycolide), polyethylene glycol, polycaprolactone like poly(ε-caprolactone), polydioxanone, polygluconate, polylactic acid-polyethylene oxide copolymers, polysaccharides, cellulose derivatives, hyaluronic acid based polymers, starch, gelatin, collagen, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(amino acids) or any polymer blends, copolymers, or derivatives. 
     
     
         51 . The method according to  claim 33 , wherein at least one layer is provided with pores having an average pore size of about 0.5-5 mm. 
     
     
         52 . The method according to  claim 33 , wherein at least one layer is provided with pores having an average pore size of about 1-4 mm. 
     
     
         53 . The method according to  claim 33 , wherein at least one layer is provided with pores having a regular or irregular shape. 
     
     
         54 . The method according to  claim 53 , wherein the pores having a regular shape have a circular, elliptical, oval or polygonal shape such as a triangular, square, pentagonal or rhomb-like shape. 
     
     
         55 . The method according to  claim 53 , wherein the pores having an irregular shape have a non-circular cross-section or a monosymmetric shape to provide an anisotropic pore structure. 
     
     
         56 . The method according to  claim 53 , wherein coplanar pores in the multi-layered structure have different pore diameters or pore shapes to provide an anisotropic pore structure. 
     
     
         57 . The method according to  claim 33 , wherein at least one layer is provided with pores having an anisotropic shape in its cross-section. 
     
     
         58 . The method according to  claim 57 , wherein the anisotropic shape of the pores tapers from the upper surface of the porous layer to the inner part thereof or the opposite side of the prosthesis. 
     
     
         59 . The method according to  claim 53 , wherein the anisotropic pore structure or the anisotropic shape of the pores is adapted to the anisotropic anatomical nature of a site at which the prosthesis is to be inserted in a patient. 
     
     
         60 . The method according to  claim 33 , wherein one, two, or more of the layers of the multi-layered structure like the porous layer or the anti-adhesion coating layer are made as drug-releasing layers by adding one or more releasable drugs, therapeutic agents and/or pharmaceutically active substances in the respective layers before molding the layers or by impregnating them into the molded layers. 
     
     
         61 . The method according to  claim 33 , further comprising the step of forming an additional polymeric drug-releasing layer on one or both outermost layers of the prosthesis, comprising one or more releasable drugs, therapeutic agents and/or pharmaceutically active substances. 
     
     
         62 . The method according to  claim 33 , wherein two layers in the multi-layered sheet structure are formed to provide a memory effect. 
     
     
         63 . The method according to  claim 62 , wherein these two layers are formed of a polymeric material as two additional layers providing the memory effect properties in the multi-layered sheet structure of the prosthesis. 
     
     
         64 . A method of treating a patient by implanting the prosthesis according to  claim 1 . 
     
     
         65 . The method according to  claim 64 , wherein the prosthesis is implanted for strengthening abdominal wall hernia defects. 
     
     
         66 . The method according to  claim 64 , wherein the prosthesis is implanted for repairing an anatomical defect of the abdominal wall, diaphragm and/or chest wall. 
     
     
         67 . The method according to  claim 64 , wherein the prosthesis is implanted for correction of defects in the genitourinary system. 
     
     
         68 . The method according to  claim 64 , wherein the prosthesis is implanted for repairing traumatically damaged organs such as the spleen, liver, kidney, lung, bladder or heart.