초록 ▼

A malleable implant for implantation into living tissue is prepared having access means for cells into the interior of the implant. The implant is capable of being deformed under pressure required to insert the implant into an implant site. The access means can be hollow or solid. The solid comprise

A malleable implant for implantation into living tissue is prepared having access means for cells into the interior of the implant. The implant is capable of being deformed under pressure required to insert the implant into an implant site. The access means can be hollow or solid. The solid comprises a material that more rapidly resorbs in vivo than the malleable implant to provide channels, or comprises a mechanically weak material that fractures under force at an implant site to produce channels or cracks. The access means may be inserted in the malleable implant at an implant site. A multilaminar structure may be formed having layers of malleable implant and layers of access means, or the access means may be heterogeneously distributed throughout the malleable implant. A kit can contain a powder such as calcium phosphate for making a paste implant material, and an access means insertable into the paste.

대표청구항 ▼

A malleable implant for implantation into living tissue is prepared having access means for cells into the interior of the implant. The implant is capable of being deformed under pressure required to insert the implant into an implant site. The access means can be hollow or solid. The solid comprise

A malleable implant for implantation into living tissue is prepared having access means for cells into the interior of the implant. The implant is capable of being deformed under pressure required to insert the implant into an implant site. The access means can be hollow or solid. The solid comprises a material that more rapidly resorbs in vivo than the malleable implant to provide channels, or comprises a mechanically weak material that fractures under force at an implant site to produce channels or cracks. The access means may be inserted in the malleable implant at an implant site. A multilaminar structure may be formed having layers of malleable implant and layers of access means, or the access means may be heterogeneously distributed throughout the malleable implant. A kit can contain a powder such as calcium phosphate for making a paste implant material, and an access means insertable into the paste. comprising calcium which is substantially not bound to albumin. 9. The structure of claim 1 being substantially free of albumin. 10. The structure of claim 1 is substantially pyrogen free. 11. The structure of claim 3 further comprising a binding agent on at least a part of the surface of the cells. 12. The structure of claim 1 further comprising an additive being selected from the group consisting of antibody, antimicrobial agent, agent for improving the biocompatibility of the structure, proteins, anticoagulants, anti-inflammatory compounds, compounds reducing graft rejection, living cells, cell growth inhibitors, agents stimulating endothelial cells, antibiotics, antiseptics, analgesics, antineoplastics, polypeptides, protease inhibitors, vitamins, cytokine, cytotoxins, minerals, interferons, hormones, polysaccharides, genetic materials, proteins promoting the growth of endothelial cells on the fibrin, growth factors, cell growth factors, growth factors for heparin bond, substances against cholesterol, pain killers, collagen, osteoblasts, chondroblasts, chondrocytes, osteoclasts, hematpoeitic cells, stromal cells, osteoprogenitor cells, drugs, anti coagulants, poly DL lactate, alginate, recombinant material, triglycerides, fatty acids, C12-C24fatty acids, collagen, and mixtures thereof. 13. The structure of claim 1, having a ratio of volume of the porous structure in its substantially dry form to the structure in its hydrated form of about 1. 14. The structure of claim 1 further comprising bone chips having a particle size of less than 2 mm. 15. The structure of claim 1 defining a powder having a grain size of less than about 1 mm. 16. A process for preparing a fibrin structure comprising the steps of: providing a solution containing at least about 5 mg/ml fibrin or fibrinogen; providing a calcium inhibiting agent; polymerizing the solution in the presence of the calcium inhibiting agent to cause at least partial cross-linking of the fibrin or fibrinogen materials to define a partially cross-linked fibrin or fibrinogen material; lyophilizing the partially cross-linked, fibrin or fibrinogen material to define a porous structure having the following physical characteristics: in its substantially dry form, a compression strain of less than 8% and a creep modulus higher than 1.5×106Pa, the compression strain and creep modulus being measured for a sample having a diameter of 5 mm on which a compression of 2500 milli Newtons is exerted with a compression ramp of 500 milli Newtons per minute, after a compression release step following an initial compression of 2500 milli Newtons with a compression ramp of 500 milli Newtons per minute, and after hydration, a porosity such that at least 50% by volume of the total porosity is formed by channels with an open cross section of more than 500 μm2. 17. The process of claim 16, wherein the calcium inhibiting agent is present in an amount sufficient for reducing the cross-linking rate so as to obtain after the lyophilizing step a plurality of spaced walls defining therebetween channels, the channels having after rehydration in cross section an open section greater than 1000 μm2. 18. The process of claim 16, wherein the calcium inhibiting agent is present in an amount sufficient for obtaining after the lyophilizing step a wall thickness of less than 100 μm. 19. The process of claim 16, wherein the calcium inhibiting agent is selected from the group consisting of: citrate salts, phosphate salts, oxalate salts and mixtures thereof. 20. The process of claim 16, wherein the polymerizing step includes an effective amount of the calcium inhibiting agent sufficient for increasing the clotting time to more than 30 seconds, said clotting time being measured at 37° C. in a stirred cuvette containing 0.5 ml of the fibrin or fibrinogen material. 21. The process of claim 16, wherein the lyophilizing step is carried out at a temperatur e of less than 40° C. and at a pressure of less than 0.4×105Pa. 22. The process of claim 16 further including the step of adding a phosphate salt to the solution in an amount sufficient for having a Ca/P ratio from about 0.5 to about 5. 23. The process of claim 16 wherein the solution is substantially free of albumin. 24. The process of claim 16 further comprising the step of adding to the solution prior to, during or after the polymerizing step a compound selected from the group consisting of: antibody, antimicrobial agent, agent for improving the biocompatibility of the structure, proteins, anticoagulants, anti-inflammatory compounds, compounds reducing graft rejection, living cells, cell growth inhibitors, agents stimulating endothelial cells, antibiotics, antiseptics, analgesics, antineoplastics, polypeptides, protease inhibitors, vitamins, cytokine, cytotoxins, minerals, interferons, hormones, polysaccharides, genetic materials, proteins promoting or stimulating the growth and/or attachment of endothelial cells on the cross-linked fibrin, growth factors, cell growth factors, growth factors for heparin bond, substances against cholesterol, pain killers, collagen, osteoblasts, chondroblasts, chondrocytes, osteoclasts, hematpoeitic cells, stromal cells, osteoprogenitor cells, drugs, anti coagulants, poly DL lactate, alginate, recombinant material, triglycerides, fatty acids, C12-C24fatty acids, and mixtures thereof or a solution containing at least one of said compound. 25. The process of claim 16 further comprising the step of after the lyophylizing step adding to the porous structure a compound selected from the group consisting of antibody, antimicrobial agent, agent for improving the biocompatibility of the structure, proteins, anticoagulants, anti-inflammatory compounds, compounds reducing graft rejection, living cells, cell growth inhibitors, agents stimulating endothelial cells, antibiotics, antiseptics, analgesics, antineoplastics, polypeptides, protease inhibitors, vitamins, cytokine, cytotoxins, minerals, interferons, hormones, polysaccharides, genetic materials, proteins promoting or stimulating the growth and/or attachment of endothelial cells on the cross-linked fibrin, growth factors, cell growth factors, growth factors for heparin bond, substances against cholesterol, pain killers, collagen, osteoblasts, chondroblasts, chondrocytes, osteoclasts, hematpoeitic cells, stromal cells, osteoprogenitor cells, anti coagulants, poly DL lactate, alginate, recombinant material, triglycerides, fatty acids, C12-C24fatty acids, drugs, and mixtures thereof or a solution containing at least one of said compound. 26. The process of claim 16, wherein during the polymerizing step less than about 50% by weight of the fibrin or fibrinogen material is cross-linked. 27. The process of claim 16, wherein the calcium inhibiting agent is an antibiotic having anticoagulant property. 28. The process of claim 16, wherein the step of polymerizing is carried out at a pH from about 6 to about 10, and at a temperature from about 0° C. to about 60° C. 29. The process of claim 16, wherein the structure can be sterilized at a temperature below 0° C. by gamma radiation at a dosage of at least about 25 kGys. 30. The process of claim 16, wherein the porous material has an osmolarity greater than 175 mosm. 31. The process of claim 16, further comprising the step of spray-freeze drying the porous structure. 32. A kit for preparing a bone substitute, said kit comprising a first chamber containing an aqueous solution containing BMP and a second container containing a fibrin or fibrinogen material having the following physical characteristics: in its substantially dry form, a compression strain of less than 8%, and a creep modulus higher than 1.5 106Pa, said compression strain and creep modulus being measured for a sample having a diameter of 5 mm on which a compression of 2500 mil li Newtons is exerted with a compression ramp of 500 milli Newtons per minute, after a compression release step following an initial compression of 2500 milli Newtons with a compression ramp of 500 milli Newtons per minute; and after hydration, such a porosity that at least 50% by volume of the total porosity is formed by channels with an open cross section of more than 500 μm2. 33. A cement for use with bones comprising: a solution containing a fibrin powder, and bone particles, the fibrin powder having the following physical characteristics: in its substantially dry form, a compression strain of less than 8%, and a creep modulus higher than 1.5×106Pa, said compression strain and creep modulus being measured for a sample having a diameter of 5 mm on which a compression of 2500 milli Newtons is exerted with a compression ramp of 500 milli Newtons per minute, after a compression release step following an initial compression of 2500 milli Newtons with a compression ramp of 500 milli Newtons per minute; and after hydration, such a porosity that at least 50% by volume of the total porosity is formed by channels with an open cross section of more than 500 μm2.