Biomaterial system for in situ tissue repair

Abstract

A method, and related composition and apparatus for repairing a tissue site. The method involves the use of a curable polyurethane biomaterial composition having a plurality of parts adapted to be mixed at the time of use in order to provide a flowable composition and to initiate cure. The flowable composition can be delivered using minimally invasive means to a tissue site and there fully cured provide a permanent and biocompatible prosthesis for repair of the tissue site. Further provided are a mold apparatus, e.g., in the form of a balloon or tubular cavity, for receiving a biomaterial composition, and a method for delivering and filling the mold apparatus with a curable composition in situ to provide a prosthesis for tissue repair.

What is claimed is:  
     
         1 . A method for repairing a tissue site, the method comprising the steps of: 
 (a) providing a curable polyurethane biomaterial composition comprising a plurality of parts adapted to be mixed at the time of use in order to provide a flowable composition and to initiate cure,    (b) mixing the composition parts in order to initiate cure and employing minimally invasive means to deliver a quantity of the curing composition to the tissue site, and    © completely curing the delivered composition to provide a permanent repair of the tissue site.    
     
     
         2 . A method according to  claim 1  wherein the composition parts comprise: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts, 
 wherein the composition is sufficiently flowable to permit it to be delivered to the tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.  
 
     
     
         3 . A method according to  claim 2  wherein the composition provides improved cure characteristics and cured properties as compared to a comparable composition lacking the reactive hydrophobic additive component.  
     
     
         4 . A method according to  claim 3  wherein the improved cure characteristics include a significant reduction in the appearance of bubbles when cured in the presence of moisture.  
     
     
         5 . A method according to  claim 1  wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.  
     
     
         6 . A method according to  claim 1  wherein the method is used to repair an orthopedic joint selected from the group consisting of diarthroidal and amphiarthroidal joints.  
     
     
         7 . A method according to  claim 6  wherein the amphiarthroidal joints are selected from the group consisting of synphysoidal joints and syndemoidal joints.  
     
     
         8 . A method according to  claim 7  wherein the synphysiodal joints are intervertebral joints.  
     
     
         9 . A method according to  claim 6  wherein the method is performed using endoscopic/arthroscopic surgical instrumentation and under fiberoptic visualization.  
     
     
         10 . A method according to  claim 9  wherein the instrumentation comprises a static mixer and delivery cannula to mix and deliver the composition.  
     
     
         11 . A curable polyurethane composition comprising a plurality of parts capable of being mixed at the time of use in order to provide a flowable composition and to initiate cure, the parts comprising: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, and one or more catalysts, 
 wherein the composition is sufficiently flowable to permit it to be delivered to a tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.    
     
     
         12 . A composition according to  claim 11  wherein the composition provides improved cure characteristics and cured properties as compared to a comparable composition lacking the reactive hydrophobic additive  
     
     
         13 . A composition according to  claim 12  wherein the hydrophobic polymer additive is present at a concentration of between about 1% and about 50% by weight, and is selected from the group consisting of hydroxyl- or amine-terminated compounds selected from the group consisting of poybutadiene, polyisoprene, polyisobutylene, silicones, polyethylenepropylenediene, copolymers of butadiene with acryolnitrile, copolymers of butadiene with styrene, copolymers of isoprene with acrylonitrile, copolymers of isoprene with styrene, and mixtures thereof.  
     
     
         14 . A composition according to  claim 12  wherein the improved cure characteristics include a significant reduction in the appearance of bubbles when cured in the presence of moisture.  
     
     
         15 . A composition according to  claim 11  wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.  
     
     
         16 . A composition according to  claim 12  wherein the improved cured properties include a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.  
     
     
         17 . A composition according to  claim 13  wherein, within the prepolymer, the polyether component is present at a concentration of between about 2% and about 10%, by weight, based on the weight of the composition, and is selected from the group consisting of linear or branched polyols with polyether backbones of polyoxyethylene, polyoxypropylene, and polytetramethylene oxide (polyoxytetramethylene), and copolymers thereof.  
     
     
         18 . A composition according to  claim 17  wherein the polyol comprises one or more polytetramethylene oxides having molecular weights in the range of 250 to 2900.  
     
     
         19 . A composition according to  claim 13  wherein the isocyanate is present in excess in the prepolymer component and comprises an aromatic (poly)isocyanate selected from the group consisting of 2,2′-, 2,4′-, and 4,4′-diphenylmethanediisocyanate (MDI), and combinations thereof.  
     
     
         20 . A kit comprising a plurality of compositions according to  claim 11 , the compositions providing different hardnesses in their cured form, for use in preparing a heterogeneous implant.  
     
     
         21 . A method according to  claim 1 , wherein the method comprises the further steps of: 
 a) providing an implantable mold apparatus comprising an expandable cavity adapted to receive and contain the flowable biomaterial composition and a conduit adapted to connect the cavity to a source of curable, flowable biomaterial composition,    b) inserting the mold apparatus to the tissue site,    c) mixing and delivering biomaterial composition to the mold in order to fill the cavity to a desired extent,    d) permitting the biomaterial composition to completely cure, and    e) employing the molded biomaterial in situ as a prosthesis at the tissue site.    
     
     
         22 . A method according to  claim 21  wherein the steps of inserting the mold apparatus, delivering the biomaterial composition, and curing the composition are each performed by minimally invasive means.  
     
     
         23 . A method according to  claim 21  wherein the cavity is provided in the form of an inflatable balloon and the method is used to prepare an intact prosthesis.  
     
     
         24 . A method according to  claim 23  wherein the method is used to repair an intervertebral disc.  
     
     
         25 . A method according to  claim 23  wherein the method is used to resurface a knee.  
     
     
         26 . A method according to  claim 21  wherein the cavity is provided in tubular form and the method is used to prepare a tubular implant.  
     
     
         27 . A method according to  claim 26  wherein the tubular implant is used to form an implant selected from the group consisting of stents, shunts and grafts.  
     
     
         28 . A method according to  claim 27  wherein the tubular implant comprises a prosthetic implant for repairing an abdominal aortic aneurysm.  
     
     
         29 . A method according to  claim 21  wherein the composition parts comprise: (1) a quasi-prepolymer component comprising the reaction product of one or more polyether polyols, one or more isocyanates, and one or more reactive hydrophobic additives, and (2) a curative component comprising one or more polyether polyols, one or more chain extenders, one or more catalysts, wherein the composition is sufficiently flowable to permit it to be delivered to the tissue site by minimally invasive means and there undergo complete cure in situ under physiologically acceptable conditions in order to provide a biocompatible material.  
     
     
         30 . A method according to  claim 29  wherein the curing composition provides an induction period of about thirty seconds to two minutes and a set time of about 3 minutes to about 15 minutes following mixing.  
     
     
         31 . A mold apparatus for forming a prosthesis in situ, the apparatus comprising an implantable, expandable cavity adapted to receive and contain a flowable, curable biomaterial, and a removable conduit adapted to connect the cavity to a source of flowable biomaterial.  
     
     
         32 . An apparatus according to  claim 31 , wherein the apparatus is adapted for use by minimally invasive means and the cavity is a provided in the form of an inflatable balloon for use in preparing an intact prosthesis.  
     
     
         33 . An apparatus according to  claim 32  wherein the balloon is adapted for use in repairing an intervertebral disc.  
     
     
         34 . An apparatus according to  claim 33  wherein the apparatus further comprises an air passageway positioned to vent the balloon in the course of filling with biomaterial.  
     
     
         35 . An apparatus according to  claim 33  further comprising distal control valves for the biomaterial conduit and air passageway, respectively.  
     
     
         36 . An apparatus according to  claim 32  wherein the balloon provides a knee prosthesis and is adapted to be permanently positioned and filled in apposition to subchondral bone.  
     
     
         37 . An apparatus according to  claim 36  wherein the balloon comprises a surface for contact with subchondral bone, the surface being provided with one or more foot pads adapted to be implanted into corresponding anchor points drilled within subchondral bone.  
     
     
         38 . An apparatus according to  claim 36  wherein the balloon comprises a surface for contact with subchondral bone, the surface being fenestrated in order to permit the passage of biomaterial from the cavity to contact with the subchondral bone.  
     
     
         39 . A surgical kit comprising an apparatus according to  claim 37  in combination with a template for use in drilling anchor points in subchondral bone at positions corresponding to those of foot pads on the apparatus.  
     
     
         40 . A surgical kit for use in preparing a prosthesis in vivo, the kit comprising (a) an implantable mold apparatus comprising an expandable cavity adapted to receive and contain a flowable, curable biomaterial, and a removable conduit adapted to connect the cavity to a source of curable, flowable biomaterial and (b) a supply of a curable, flowable polyurethane biomaterial composition.  
     
     
         41 . A prosthesis for repairing an intervertebral disc, the prosthesis comprising an expanded mold cavity containing a cured, biocompatible, polyurethane biomaterial composition, the prosthesis providing a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.  
     
     
         42 . A prosthesis for repairing the surface of a knee joint, the prosthesis comprising a cured, biocompatible, polyurethane biomaterial composition providing a hardness of about 60 Shore to about 95 Shore, and a tensile strength (measured in the dry stage) of between about 6,000 psi and about 10,000 psi.  
     
     
         43 . A prosthesis according to  claim 42  wherein the prosthesis is heterogeneous, comprising a plurality of cured polyurethane compositions, in order to provide layers having one or more different properties.  
     
     
         44 . A prosthesis according to  claim 42  wherein the cured biomaterial is provided within a mold cavity and the prosthesis is adapted to be permanently positioned in apposition to subchondral bone.  
     
     
         45 . A prosthesis according to  claim 43  wherein the mold cavity is provided in the form of a balloon comprising a surface for contact with subchondral bone, the surface being provided with one or more foot pads adapted to be implanted into corresponding anchor points drilled within subchondral bone.