Method and apparatus for biodegradable, osteogenic, bone graft substitute device

• US 5,755,792 A
• Filed: 06/07/1995
• Issued: 05/26/1998
• 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): ISABELLA, DAVID J
• Application Number:
  US08/484,649
• Time in Patent Office: 1,084 Days
• Field of Search: 623/1, 623/11, 623/12, 623/15, 623/17, 623/16, 623/66
• US Class Current: 128/898
• 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 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• 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 2300/438 Antigens
• 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 processes 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 method for treating a structural tissue deficiency, comprising the steps of:

a) forming a porous macrostructure comprised of a biodegradable polymer in the form of a porous structure having voids;

b) forming a porous microstructure in the voids of the formed porous macrostructure with the microstructure located in the voids and being carried and supported by the porous macrostructure to form a marco-microstructure complex;

c) introducing into the complex a substance, selected from the group consisting of active and therapeutic agents; and

d) inserting the complex into the structural deficiency.

2. The method of claim 1, wherein the agent is introduced into the complex prior to the step of inserting the complex into the structural deficiency.

3. The method of claim 1, wherein the microstructure is a carrier for the substance, selected from the group consisting of active and therapeutic agents, for transporting such agent into the cavities.

4. The method of claim 3, wherein the microstructure is in the form of a meshwork of randomly shaped, positioned and sized voids.

5. The method of claim 3, wherein the agent is evenly distributed in the microstructure.

6. The method of claim 3, wherein the substance is selected from the group consisting of drugs, biological modifiers, proteins, and antigens.

7. The method of claim 1, wherein the microstructure is a chemotactic substance for causing cell migration to and aggregation into the cavities by chemotaxis.

8. The method of claim 7, wherein the chemotactic substance is hyaluronic acid.

9. The method of claim 1, wherein the microstructure has incorporated therein a solution containing the substance selected from the group consisting of active and therapeutic agents for promoting growth of tissue in the cavities when the complex is inserted into the structural deficiency.

10. The method of claim 1, wherein the microstructure is an electronegative substance which provides an electronegative environment with respect to the structural tissue deficiency for promoting growth of tissue in the voids.

11. The method of claim 1, wherein the microstructure is a biologically active substance for promoting growth of tissue in the cavities.

12. The method of claim 1, wherein the microstructure is a hydrophilic substance for attracting body fluid to the cavities.

13. The method of claim 1, wherein the voids interconnect with each void communicating with all the others and with substantially the entire exterior of the porous macrostructure.

14. A method for treating a structural tissue deficiency, comprising the steps of:

a) forming a porous macrostructure comprised of a biodegradable polymer having interconnecting voids, generally with each void communicating with all the others and with substantially the entire exterior of the porous macrostructure;

b) forming a microstructure in the interconnecting voids of the porous macrostructure with the microstructure being carried and supported by the porous macrostructure to form a marco-microstructure complex;

c) introducing into the complex a substance from the group consisting of active and therapeutic agents; and

d) inserting the complex into the structural deficiency.

15. The method of claim 14, wherein the microstructure is a carrier for the substance, selected from the group consisting of active and therapeutic agents, for transporting such agent into the cavities.

16. The method of claim 15, wherein the microstructure is in the form of a meshwork of randomly shaped, positioned and sized voids.

17. The method of claim 14, wherein the microstructure is a chemotactic substance for causing cell migration to and aggregation into the cavities by chemotaxis.

18. The method of claim 17, wherein the chemotactic substance is hyaluronic acid.

19. The method of claim 14, wherein the microstructure has incorporated therein a solution containing the substance selected from the group consisting of active and therapeutic agents for promoting growth of tissue in the cavities when the complex is inserted into the structural deficiency.

20. The method of claim 14, wherein the microstructure is a hydrophilic substance for attracting body fluid to the cavities.