Osteogenic Device for Inducing Bone Formation in Clinical Contexts

Abstract

This invention relates to an osteogenic device for the de novo induction of bone formation in a mammal. The device contains a at least one transforming growth factor—&bgr;3 isoform and a retention matrix. The device is introduced by direct injection or surgical implantation into an area where de novo bone formation is desired and, once implanted, the retention matrix acts to retain the TGF-&bgr;3 isoform at its place of introduction and forms a scaffold for generated bone, the induction of which is promoted by the TGF-&bgr;3 isoform. The device may be used to induce bone growth where bone has been debrided in a surgical procedure and it may also be used to transform neoplastic primary and/or metastatic secondary masses into bone thus facilitating surgical debridement thereof.

1 : An osteogenic device for the de novo induction of bone formation in a mammal said osteogenic device comprising an effective concentration of a transforming growth factor (TGF) and a retention matrix, the device being introducible, in use, into a mammal at a site where de novo induction of bone is desired, the retention matrix acting to retain the TGF substantially at its place of introduction and to form a scaffold for generated bone, the induction of which is promoted by the TGF. 
     
     
         2 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is deliverable into the mammal by implantation into an area where de novo bone formation is desired. 
     
     
         3 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is deliverable into the mammal by direct injection. 
     
     
         4 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is deliverable into the mammal by surgical implantation. 
     
     
         5 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is used to generate bone orthotopically. 
     
     
         6 : The osteogenic device as claimed in  claim 5  in which the bone is generated at a site where bone has been removed. 
     
     
         7 : The osteogenic device as claimed in  claim 6  in which the bone was removed in a debridement procedure carried out to treat neoplastic or inflammatory or infective lesions. 
     
     
         8 : The osteogenic device as claimed in  claim 7  in which the bone was removed from the mandible of a human primate. 
     
     
         9 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is used to generate bone heterotopically. 
     
     
         10 : The osteogenic device as claimed in  claim 9  the bone is generated in the rectus abdominis muscle of a primate. 
     
     
         11 : The osteogenic device as claimed in  claim 1  in which the osteogenic device is injected directly into neoplastic primary and/or metastatic secondary masses causing direct neoplastic transformation of the mass into bone thus facilitating its surgical debridement. 
     
     
         12 : The osteogenic device as claimed in  claim 1  in which the osteogenic device includes morsellised muscle fragments. 
     
     
         13 : The osteogenic device as claimed in  claim 12  in which the muscle fragments are rectus abdominis muscle fragments, which contain large numbers of responding cells. 
     
     
         14 : The osteogenic device as claimed in  claim 13  in which the device also includes morsellized fragments of bone. 
     
     
         15 : The osteogenic device as claimed in  claim 1  in which the osteogenic device includes morsellized fragments of bone. 
     
     
         16 : The osteogenic device as claimed in  claim 15  in which the osteogenic device contains fragments of autogenous bone. 
     
     
         17 : The osteogenic device as claimed in  claim 16  in which the device also includes morsellised muscle fragments. 
     
     
         18 : The osteogenic device as claimed in  claim 1  in which the TGF is a TGF-β isoform. 
     
     
         19 : The osteogenic device as claimed in  claim 18  in which the TGF-β isoform is a TGF-β3 isoform. 
     
     
         20 : The osteogenic device as claimed in  claim 19  in which the TGF-β3 isoform is a human TGFβ3 isoform. 
     
     
         21 : The osteogenic device as claimed in  claim 20  in which the human TGFβ3 isoform is a recombinant isoform. 
     
     
         22 : A method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal, said method comprising combining an effective concentration of a TGF and a retention matrix to form a delivery vehicle which is introducible, in use, into a mammal at a site where de novo induction of bone is desired, the retention matrix acting to retain the TGF substantially at its place of introduction and to form a scaffold for generated bone, the induction of which is promoted by the TGF. 
     
     
         23 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which the osteogenic delivery vehicle is deliverable into the mammal by implantation into an area where de novo bone formation is desired. 
     
     
         24 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 23  in which the osteogenic delivery vehicle is deliverable into the mammal by direct injection. 
     
     
         25 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 23  in which the osteogenic delivery vehicle is deliverable into the mammal by surgical implantation. 
     
     
         26 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which the osteogenic delivery vehicle is used to generate bone orthotopically. 
     
     
         27 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 26  in which the bone is generated at a site where bone has been removed. 
     
     
         28 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 27  in which the bone was removed in a debridement procedure carried out to treat neoplastic or inflammatory or infective lesions. 
     
     
         29 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 28  in which the bone was removed from the mandible of a human primate. 
     
     
         30 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which the osteogenic device is used to generate bone heterotopically. 
     
     
         31 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 30  in which the bone is generated in the rectus abdominis muscle of a primate. 
     
     
         32 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which the osteogenic device is injected directly into neoplastic primary and/or metastatic secondary masses causing direct neoplastic transformation of the mass into bone thus facilitating its surgical debridement. 
     
     
         33 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which morsellized muscle fragments are added to the device. 
     
     
         34 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 33  in which the muscle fragments are rectus abdominis muscle fragments, which contain large numbers of responding cells. 
     
     
         35 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 34  in which the device also includes morsellized fragments of bone. 
     
     
         36 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  which includes adding morsellized fragments of bone. 
     
     
         37 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 36  in which the morsellized fragments of bone are autogenous bone. 
     
     
         38 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 37  in which morsellised muscle fragments are also added to the device. 
     
     
         39 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 22  in which the TGF is a TGF-β isoform. 
     
     
         40 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 39  in which the TGF-β isoform is a TGF-β3 isoform. 
     
     
         41 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 40  in which the TGF-β3 isoform is a human TGFβ3 isoform. 
     
     
         42 : The method of producing an osteogenic delivery vehicle for the de novo induction of bone formation in a mammal as claimed in  claim 41  in which the human TGFβ3 isoform is a recombinant isoform. 
     
     
         43 : The method of inducing de novo bone formation in a mammal comprising introducing an osteogenic device as claimed in  claim 1  into a mammal at a site where de novo formation of bone is desired. 
     
     
         44 : The method of inducing orthotopical de novo bone formation in a mammal as claimed in  claim 43  in which the device is introduced at a site where bone has been removed. 
     
     
         45 : The method of inducing orthotopical de novo bone formation in a mammal as claimed in  claim 44  in which the device is introduced into the mandible of a human primate where bone has been removed. 
     
     
         46 : The method of inducing heterotopical de novo bone formation in a mammal as claimed in  claim 43  in which the device is introduced at a site where heterotopical bone formation is desired. 
     
     
         47 : The method of inducing heterotopical de novo bone formation in a mammal as claimed in  claim 46  in which the device is introduced into the rectus abdominis muscle of a primate. 
     
     
         48 : The method of transforming neoplastic primary and/or metastatic secondary masses, to cause direct inductive transformation of the mass into bone thus facilitating surgical debridement thereof comprising injecting an osteogenic device as claimed in  claim 1  directly into said neoplastic primary and/or metastatic secondary masses. 
     
     
         49 : The method of treating cancer comprising injecting an osteogenic device as claimed in  claim 1  directly into neoplastic primary and/or metastatic secondary masses, waiting for transformation of the mass into bone and surgically debriding the transformed mass.