Apparatus for biodegradable, osteogenic, bone graft substitute device

• US 5,366,508 A
• Filed: 07/07/1992
• Issued: 11/22/1994
• Est. Priority Date: 01/28/1986
• Status: Expired due to Term

• Current Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Original Assignee: THM Biomedical, Inc. (DSM-Firmenich AG)
• Inventors: Brekke, John H.
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): Nguyen, Dinh X.
• Application Number:
  US07/909,605
• Time in Patent Office: 868 Days
• Field of Search: 623/11, 623/12, 623/16, 623/18, 623/66, 424/422, 424/423, 424/424
• US Class Current: 623/23.58
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/30756 Cartilage endoprostheses A61F2/3603 takes precedence
• CPC Class Codes: A61F 2/3601 for replacing only the epiphyseal or metaphyseal parts of the femur, e.g. endoprosthetic femoral heads or necks directly fixed to the natural femur by internal fixation devices non-prosthetic internal fixation devices for the femoral head or neck A61B17/74
• CPC Class Codes: A61F 2/4601 for introducing bone substitute, for implanting bone graft implants or for compacting them in the bone cavity
• CPC Class Codes: A61F 2002/2817 Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
• CPC Class Codes: A61F 2002/2839 Bone plugs or bone graft dowels
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30261 parallelepipedal
• CPC Class Codes: A61F 2002/30461 sutured, ligatured or stitched
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/4649 Bone graft or bone dowel harvest sites
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2220/0075 sutured, ligatured or stitched, retained or tied with a rope, string, thread, wire or cable
• CPC Class Codes: A61F 2230/0082 parallelepipedal
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 27/36 containing ingredients of undetermined constitution or reaction products thereof , e.g. transplant tissue, natural bone, extracellular matrix isolated natural compounds, e.g. collagen A61L27/24
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/48 : with macromolecular fillers
• CPC Class Codes: A61L 27/54 : Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 : Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 : Materials at least partially resorbable by the body
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Device and method for treating mammalian bone deficiencies, defects, voids and conformational discontinuities produced by congenital deformities, osseous and/or soft tissue pathology, traumatic injuries and functional atrophy is described. The device is a one piece molded body member composed of four substances, each of which contributes to the device, a specific requirement (or requirements) for osteogenesis and/or osteoneogenesis. Taken as a whole, the functions of these device constituents are integrated into a single body member which, when implanted into a bone defect, has the capacity to restore functional architecture and mechanical integrity, initiate osteoinduction and osteogenesis, and maintain the biological process of bone formation and remodeling while the host organism is simultaneously biodegrading the body member. The ultimate result of the functioning is formation of healthy, viable bone tissue where there was not bone before, while, simultaneously, the entire device is hydrolyzed and completely metabolized by the host organism. The device comprises four disparate elements: POLYLACTIC ACID, HYALURONIC ACID BONE MORPHOGENETIC PROTEIN and BONE DERIVED GROWTH FACTOR. Working together, these elements provide the following five biological functions prerequisite to the processes of osteoneogenesis: structural competence (polylactic acid), chemotaxis (hyaluronic acid), electronegative field (hyaluronic acid and physical-chemical electrokinetic events), osteoinduction (bone morphogenetic protein), and osteogenesis (bone derived growth factor).

Claims

1. A biodegradable device for facilitating healing of structural voids in bone, cartilage as well as soft tissue comprising, in combination:

a. a porous macrostructure, formed from a biodegradable polymer, providing a porous architecture as well as structural and mechanical integrity to the structural void being treated, with the porous macrostructure including interconnecting voids; and

b. a porous microstructure, formed from a chemotactic ground substance and located in the interconnecting voids of the porous macrostructure and carried by and separate from the biodegradable polymer forming the porous macrostructure.

2. The device of claim 1 further comprising, in combination:

at least one biologically active agent carried at a location selected from the group consisting of in the porous macrostructure formed by the biodegradable polymer, in the porous microstructure formed by the chemotactic ground substance, and between the porous macrostructure and the porous microstructure.

3. The device of claim 2 wherein said chemotactic ground substance is selected from the group consisting of compounds of glycoproteins and compounds of glycosaminoglycans.

4. The device of claim 2 wherein the interconnecting voids of the porous macrostructure are defined by the biodegradable polymer formed into incomplete partitions having exposed surfaces, wherein said biologically active agent is incorporated into the macrostructural polymer, thus residing in part on the exposed surfaces of the incomplete partitions and in part within the incomplete partitions.

5. The device of claim 2 wherein the interconnecting voids of the porous macrostructure are defined by the biodegradable polymer formed into incomplete partitions having surfaces, wherein said biologically active agent is adhered to the macrostructural polymer and resides exclusively on the surfaces of the incomplete partitions.

6. The device of claim 2 wherein said biologically active agent is incorporated into the chemotactic ground substance.

7. The device of claim 2 wherein the porous microstructure includes voids having interstices, and wherein said biologically active agent is carried by entrapment in the interstices of the porous microstructure.

8. The device of claim 2 wherein the interconnecting voids of the porous macrostructure are defined by the biodegradable polymer formed into incomplete partitions, wherein said biologically active agent is carried by entrapment between the incomplete partitions and the porous microstructure.

9. The device of claim 2 wherein said biodegradable polymer is selected from the group consisting of a homogeneous poly(hydroxy) acid and a copolymer of at least two poly(hydroxy) acids.

10. The device of claim 2 in which the biologically active agent is osteoinductive and osteogenic agents selected from the consisting of bone morphogenetic proteins and bone derived growth factor.

11. The device of claim 1 wherein said device is in the form of a bone substitute.

12. The device of claim 1 wherein said device is in the form of a cartilage substitute.

13. The device of claim 1 wherein said device is in the form of a soft tissue substitute.

14. The device of claim 1 wherein said chemotactic ground substance is derived from the group consisting of compounds of glycoproteins and compounds of glycosaminoglycans.

15. The device of claim 14 in which the chemotactic ground substance microstructure is selected from the group consisting of glycosamino glycans, glycoproteins, lamin and type IV collagen.

16. The device of claim 1 wherein the biodegradable polymer is preformed into the porous macrostructure prior to the introduction of the chemotactic ground substance.

17. The device of claim 16 wherein the chemotactic ground substance is selected from the group consisting of a velour, felting and loosely woven sheet, prior to the introduction of the chemotactic ground substance into the porous macrostructure, wherein said velour, felting, or loosely woven sheet are adhered to the preformed porous macrostructure of the biodegradable polymer within the interconnecting voids of the porous macrostructure.

18. The device of claim 16 wherein the interconnecting voids of the porous macrostructure are randomly shaped, sized and positioned in the porous macrostructure, with the interconnecting voids of the porous macrostructure being formed by incomplete partitions of the biodegradable polymer.

19. The device of claim 18 in which the chemotactic ground substance is in a form selected from the group consisting of:

a. a solid sheet adhered to the preformed incomplete partitions of the biodegradable polymer;

b. an open laced network of strands adhered to the preformed biodegradable polymer incomplete partitions;

c. a velour, felting or loosely woven sheet adhered to the preformed biodegradable polymer incomplete partitions; and

,

d. an open cell meshwork mass that is carried within the interconnected voids of the porous macrostructure and is only incidentally adhered to the preformed biodegradable polymer incomplete partitions.

20. The device of claim 1 wherein said biodegradable polymer is selected from the group consisting of a homogeneous poly(hydroxy) acid and a copolymer of at least two poly(hydroxy) acids.

22. The device of claim 1 wherein said device is a carrier for at least one of the group consisting of drugs, biological modifiers, proteins, and angigens.

21. The device of claim 2o wherein said biodegradable polymer is selected from the group consisting of D,L-polylactic acid, L-polylactic acid, glycolic acid and co-polymers thereof.