Bone graft material for osseous defects and method of making same

• US 4,394,370 A
• Filed: 09/21/1981
• Issued: 07/19/1983
• Est. Priority Date: 09/21/1981
• Status: Expired due to Term

• Current Assignee: Gensci Orthobiologics, Inc. (Orthofix Medical Inc.)
• Original Assignee: Steven R. Jefferies
• Inventors: Jefferies, Steven R.
• Primary Examiner(s): Morris, Theodore
• Application Number:
  US06/304,367
• Time in Patent Office: 666 Days
• Field of Search: 106/161, 106/122, 424/15, 424/14, 424/95
• US Class Current: 606/76
• CPC Class Codes: A61F 2002/2835 Bone graft implants for filling a bony defect or an endoprosthesis cavity, e.g. by synthetic material or biological material
• CPC Class Codes: A61F 2002/30059 differing in bone mineralization, e.g. made from both mineralized and demineralized adjacent parts
• CPC Class Codes: A61F 2310/00365 Proteins; Polypeptides; Degradation products thereof
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61L 27/24 Collagen
• CPC Class Codes: A61L 27/3608 Bone, e.g. demineralised bone matrix [DBM], bone powder
• CPC Class Codes: A61L 27/365 Bones
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: Y10S 530/84 Bones; tendons; teeth; cartilage

Abstract

Complexes of reconstituted collagen and demineralized bone particles or reconstituted collagen and a solubilized bone morphogenetic protein fabricated in a sponge suitable for in vivo implantation in osseous defects are disclosed. Both demineralized bone particles (DBP) and bone morphogenetic protein have demonstrated the ability to induce the formation of osseous tissue in animal and human experiments. Reconstituted collagen conjugate is highly biocapatible and can be fabricated in a variety of configurations, especially as a sponge. This material can be used as a grafting implant in plastic and reconstructive surgery, periodontal bone grafting, and in endodontic procedures. Structural durability is enhanced by cross-linking with glutaraldehyde which is also used to sterilize and disinfect the collagen conjugate prior to implantation.

Claims

1. A bone graft material capable of inducing the formation of osseous tissue in the animal in which it is implanted, said bone graft material consisting essentially of a collagen conjugate containing:

from about 65 to about 95 weight percent reconstituted collagen having dispersed substantially uniformly therein

from about 35 to about 5 weight percent of (a) demineralized bone particles, (b) solubilized bone morphogenic protein, or (c) mixtures of demineralized bone particles and solubilized bone morphogenic protein,

said bone graft material adapted to induce the formation of osseous tissue when implanted in an animal.

2. The bone graft material of claim 1 further including a cross-linking amount of glutaraldehyde to confer additional structural integrity to the bone graft material.

3. The bone graft material of claim 1 or 2 wherein the demineralized bone powder, when present, has a particle size of no greater than about 70 millimicrons.

4. A lyophilized sponge for in vivo implantation composed of the bone graft material of claim 1.

5. A lyophilized sponge for in vivo implantation composed of the bone graft material of claim 2.

6. A lyophilized sponge for in vivo implantation composed of the bone graft material of claim 3.

7. The bone graft material of claim 1 or 2 wherein the amount of reconstituted collagen is about 80 to about 90% and the amount of (a), (b) or (c) is about 20 to about 10%.

8. The bone graft material of claim 2 wherein the gluteraldehyde is present in an amount of about 1 to about 5 weight percent.

9. The bone graft material of claim 1, 2 or 8 wherein the reconstituted collagen is complexed with alkaline phosphatase.

10. A biocompatible bone graft material composed of a collagen conjugate and capable of inducing the formation of osseous tissue in the animal in which it is implanted, said bone graft material consisting essentially of, in weight percent:

(i) from about 65 to about 95% reconstituted collagen complexed with alkaline phosphatase, the collagen having dispersed substantially uniformly therein

(ii) from about 35% to about 5% of dimineralized bone particles, and

(iii) a cross-linking amount of gluteraldehyde to confer structural integrity to the bone graft material,

said bone graft material adapted to induce osteogenesis, substantially non-inflammatory and biocompatible with the tissue in the animal in which it is implanted.

12. The bone graft material of claim 10 or 11 wherein the amount of gluteraldehyde is from about 1 to about 5%.

11. A biocompatible bone graft material composed of a collagen conjugate and capable of inducing the formation of osseous tissue in the animal in which it is implanted, said bone graft material consisting essentially of, in weight percent:

(i) from about 65 to about 95% reconstituted collagen complexed with alkaline phosphatase, the collagen having dispersed substantially uniformly therein

(ii) from about 35 to about 5% of solubilized bone morphogenic protein, and

(iii) a cross-linking amount of gluteraldehyde to confer structural integrity to the bone graft material,

said bone graft material adapted to induce osteogenesis, substantially non-inflammatory and biocompatible with the tissue in the animal in which it is implanted.