초록 ▼

Methods, devices and compositions for fusing adjacent vertebrae, and otherwise localizing bone growth, are provided. In one form of the invention, a method for fusing adjacent vertebrae includes preparing a disc space for receipt of an intervertebral disc implant in an intervertebral disc space betw

Methods, devices and compositions for fusing adjacent vertebrae, and otherwise localizing bone growth, are provided. In one form of the invention, a method for fusing adjacent vertebrae includes preparing a disc space for receipt of an intervertebral disc implant in an intervertebral disc space between adjacent vertebrae, inserting the implant into the intervertebral disc space and providing an osteoinductive composition that includes an osteoinductive factor in a pharmaceutically acceptable carrier. The carrier is advantageously substantially impermeable to efflux of the osteoinductive factor and is released as the carrier is resorbed or biodegraded. Preferred carriers include a hardened, resorbable carrier, such as a calcium phosphate cement that retains at least about 50% of the osteoinductive factors greater than about 2 days. Preferred osteoinductive factors are growth factors and include bone morphogenetic proteins and LIM mineralization proteins. In alternative forms of the invention, the method may be performed without utilization of a load-bearing spinal implant by disposing the osteoinductive composition in the disc space. The method is advantageously performed on lumbar vertebrae by a posterior approach. Intervertebral fusion devices and methods for their preparation are also provided.

대표청구항 ▼

1. A method of generating a bone mass to fuse adjacent vertebrae in a spine of a patient, comprising: preparing a flowable composition for generating said bone mass, said composition including an osteoinductive substance homogeneously entrained within a slow release biodegradable calcium phosphate c

1. A method of generating a bone mass to fuse adjacent vertebrae in a spine of a patient, comprising: preparing a flowable composition for generating said bone mass, said composition including an osteoinductive substance homogeneously entrained within a slow release biodegradable calcium phosphate cement carrier that hardens so as to be impermeable to efflux of the osteoinductive substance in vivo sufficiently that the formed bone mass is confined to the volume of the carrier when implanted, and wherein the carrier gradually exposes the entrained osteoinductive substance at said location as it degrades, and further wherein the osteoinductive substance comprises a bone morphogenic protein present in an amount of from about 2 mg/ml to about 4 mg/ml of the calcium phosphate cement carrier; and introducing said composition in a location between the said vertebrae, wherein said carrier comprises collagen fibers and has a calcium to phosphate ratio of about 0.4 to about 0.6 and the calcium phosphate comprises amorphous calcium phosphate. 2. The method of claim 1, wherein said bone morphogenetic protein is a recombinant human protein. 3. The method of claim 2, wherein said recombinant protein is selected from rhBMP-2, rhBMP-7, heterodimers thereof and combinations thereof. 4. The method of claim 1, wherein said bone morphogenetic protein is selected from the group consisting of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, heterodimers thereof and combinations thereof. 5. The method of claim 1, wherein said osteoinductive substance comprises an osteoinductive factor selected from the group consisting of LIM mineralization protein, growth and differentiation factors, cartilage-derived morphogenic proteins, transforming growth factors, insulin-like growth factors, epidermal growth factors, platelet-derived growth factors and fibroblast growth factors. 6. The method of claim 1, wherein said carrier has a substantially closed porous structure having internal cells, and said osteoinductive substance is trapped within said cells, so that the erosion of said carrier exposes said cells and said osteoinductive composition is released from said cells. 7. The method of claim 1, wherein said carrier has an initial volume, and said bone mass replaces said initial volume of said carrier as said carrier is resorbed. 8. The method of claim 1, wherein said preparing includes adding said osteoinductive substance in a liquid form to said calcium phosphate cement in a powder form and mixing to a putty-like consistency. 9. The method of claim 1, wherein said composition is flowable at a temperature of about 45 degrees Celsius or higher and hardens at about body temperature, and said introducing is performed when said composition is at a temperature of about 45 degrees Celsius or higher. 10. A method for fusing adjacent vertebrae in a patient by a posterior or transforaminal fusion approach, comprising: preparing a disc space for receipt of an intervertebral disc implant in an intervertebral space between adjacent vertebrae, said implant configured to retain an osteoinductive composition, wherein said preparing is by a posterior or transforaminal approach that exposes a hematoma site or scar tissue site susceptible to contact by a diffusible osteoinductive factor; and introducing a flowable composition for generating bone mass in a location between the said vertebrae, said composition including an osteoinductive substance homogeneously entrained within a slow release biodegradable calcium phosphate cement carrier that hardens so as to be impermeable to efflux of the osteoinductive substance in vivo sufficiently that the formed bone mass is confined to the volume of the carrier when implanted, and wherein the carrier gradually exposes the entrained osteoinductive substance at said location as it degrades, and further wherein the osteoinductive substance comprises a bone morphogenic protein in an amount of from about 2 mg/ml to about 4 mg/ml of the calcium phosphate cement carrier, wherein said carrier comprises collagen fibers and has a calcium to phosphate ratio of about 0.4 to about 0.6 and the calcium phosphate comprises amorphous calcium phosphate. 11. The method of claim 10, wherein said introducing step includes providing an implant having a chamber for retaining said composition and placing said composition inside said implant chamber. 12. The method of claim 11, wherein said implant is biodegradable or resorbable. 13. The method of claim 10, wherein said bone morphogenetic protein is a recombinant human protein. 14. The method of claim 13, wherein said recombinant protein is selected from rhBMP-2, rhBMP-7, heterodimers thereof and combinations thereof. 15. The method of claim 10, wherein said bone morphogenetic protein is selected from the group consisting of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14, BMP-15, BMP-16, BMP-17, BMP-18, heterodimers thereof and combinations thereof. 16. The method of claim 10, wherein said osteoinductive substance comprises an osteoinductive factor selected from the group consisting of LIM mineralization protein, growth and differentiation factors, cartilage-derived morphogenic proteins, transforming growth factors, insulin-like growth factors, epidermal growth factors, platelet-derived growth factors and fibroblast growth factors. 17. The method of claim 10, wherein less than about 50% by weight of the osteoinductive substance is released from the carrier after about 2 days post implantation. 18. The method of claim 17, wherein less than about 50% by weight of the osteoinductive substance is released from the carrier after about 7 days post implantation. 19. A spinal fusion device, comprising: a composition comprising an osteoinductive composition present in an amount effective to induce bone growth to form a bone mass in a location for fusing adjacent vertebrae, said osteoconductive composition entrained within a slow release biodegradable calcium phosphate cement carrier, wherein said carrier comprises collagen fibers and has a calcium to phosphate ratio of about 0.4 to about 0.6 that hardens so as to be substantially impermeable to efflux of the osteoinductive composition in vivo sufficiently that the formed bone mass is confined to the volume of the carrier when implanted; wherein the carrier gradually exposes the entrained osteoinductive composition at said location as it degrades, and further wherein the osteoinductive composition comprises a bone morphogenic protein present in an amount of from about 2 mg/ml to about 4 mg/ml of the calcium phosphate cement carrier and the calcium phosphate comprises amorphous calcium phosphate; and a spinal fusion cage.