Resorbable Bioceramic Compositions of Poly-4-Hydroxybutyrate and Copolymers

Abstract

Compositions for making implants comprising high levels of resorbable bioceramics have been developed. These compositions comprise P4HB and copolymers thereof filled with bioceramics, and can be prepared with high levels of bioceramic without the compositions becoming too brittle for the intended application. A preferred embodiment comprises P4HB filled with β-TCP.

We claim: 
     
         1 . A biocompatible composition comprising poly-4-hydroxybutyrate polymer or copolymer thereof, wherein the poly-4-hydroxybutyrate polymer or copolymer has a weight average molecular weight between 1,000 and 800,000 Da, and a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition. 
     
     
         2 . The composition of  claim 1  wherein the bioceramic is α-tricalcium phosphate (TCP), β-TCP, a combination of α- and β-TCP, biphasic calcium phosphate (BCP), hydroxylapatite, calcium sulfate, calcium carbonate, or a calcium phosphate salt-based bioceramic. 
     
     
         3 . The composition of  claim 1  wherein the composition comprises a blend of one or more polymers with poly-4-hydroxybutyrate polymer or copolymer thereof. 
     
     
         4 . The composition of  claim 3  wherein the polymers are resorbable. 
     
     
         5 . The composition of  claim 4  wherein the one or more polymers are derived from glycolic acid, glycolide, lactic acid, lactide, p-dioxanone, trimethylene carbonate, or ε-caprolactone monomers. 
     
     
         6 . The composition of  claim 5  wherein the polymer is poly-L-lactic acid or poly-DL-lactic acid. 
     
     
         7 . A medical device comprising a biocompatible composition of  claim 1 , wherein the poly-4-hydroxybutyrate polymer or copolymer thereof has a weight average molecular weight between 1,000 and 800,000 Da, and a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition. 
     
     
         8 . The device of  claim 7  wherein the device is formed by injection molding of the composition, extrusion of the composition, or by machining a modeled form of the composition. 
     
     
         9 . The device of  claim 8  selected from the group consisting of a suture anchor, screw, pin, bone plate, interference screw, tack, fastener, rivets, staples, tissue engineering scaffold, rotator cuff repair device, meniscus repair device, guided tissue repair/regeneration device, articular cartilage repair device, tendon repair device, ligament repair device, fixation device for an implant, fixation device for a plastic surgery device including facial and breast cosmetic and reconstructive devices, fixation device for a surgical mesh, facial reconstructive device, spinal fusion device, device for treatment of osteoarthritis, imaging device, and bone graft substitute. 
     
     
         10 . The device of  claim 7  having a tensile modulus of >50,000 psi (>0.34 MPa). 
     
     
         11 . The device of  claim 9  wherein the fixation device is used to fix surgical mesh to bone. 
     
     
         12 . The device of  claim 9  wherein the fixation device is used for a brow-lift. 
     
     
         13 . The device of  claim 7  wherein the device further comprises a bioactive agent, contrast agent, radiopaque marker and/or a radioactive substance. 
     
     
         14 . The bioactive agent of  claim 13  wherein the bioactive agent is a small-molecule drug, peptide, protein, antibody, sugar, polysaccharide, nucleotide, oligonucleotide, hyaluronic acid or derivatives thereof, aptamer, siRNA, or nucleic acid. 
     
     
         15 . A method of preparing a biocompatible composition comprising poly-4-hydroxybutyrate polymer or copolymer thereof, wherein the polymer or copolymer has a weight average molecular weight between 1,000 and 800,000 Da, and a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition, comprising providing powder or pellets of the poly-4-hydroxybutyrate polymer or copolymer thereof and the bioceramic, heating to a melt temperature in the range of 150 to 300° C., and extruding the melted composition. 
     
     
         16 . A method of preparing a biocompatible composition comprising injection molding at a melt temperature in the range of 150 to 300° C., a poly-4-hydroxybutyrate polymer or copolymer thereof, wherein the polymer or copolymer has a weight average molecular weight between 1,000 and 800,000 Da, together with a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition. 
     
     
         17 . A method of preparing a biocompatible composition comprising solvent blending a poly-4-hydroxybutyrate polymer or copolymer thereof, wherein the polymer or copolymer has a weight average molecular weight between 1,000 and 800,000 Da, together with a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition. 
     
     
         18 . A method of preparing a device comprising a biocompatible composition comprising a poly-4-hydroxybutyrate polymer or copolymer thereof, wherein the polymer or copolymer has a weight average molecular weight between 1,000 and 800,000 Da, together with a resorbable bioceramic comprising up to 70% by weight or 50% by volume of the composition, comprising machining a molded rod of the composition to produce the required device design. 
     
     
         19 . The device of  claim 7  wherein the device is formed by extrusion of the composition or by machining an extruded form of the composition.