Biodegradable implant for fracture nonunions

• US 5,492,697 A
• Filed: 03/13/1995
• Issued: 02/20/1996
• Est. Priority Date: 03/05/1990
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Heckman, James D., Agrawal, Chandra M., Boyan, Barbara D.
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US08/403,513
• Time in Patent Office: 344 Days
• Field of Search: 424/422, 424/426, 623/11
• US Class Current: 623/16.11
• CPC Class Codes: A61F 2/28 Bones joints A61F2/30
• CPC Class Codes: A61F 2/3094 Designing or manufacturing processes
• 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 2002/30004 the prosthesis being made from materials having different values of a given property at different locations within the same prosthesis
• CPC Class Codes: A61F 2002/30062 (bio)absorbable, biodegradable, bioerodable, (bio)resorbable, resorptive
• CPC Class Codes: A61F 2002/30065 thermoplastic, i.e. softening or fusing when heated, and hardening and becoming rigid again when cooled
• CPC Class Codes: A61F 2002/30113 circular
• CPC Class Codes: A61F 2002/302 toroidal, e.g. rings
• CPC Class Codes: A61F 2002/30225 Flat cylinders, i.e. discs
• CPC Class Codes: A61F 2002/30677 Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
• CPC Class Codes: A61F 2002/30785 parallel
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2210/0071 thermoplastic
• CPC Class Codes: A61F 2230/0006 circular
• CPC Class Codes: A61F 2230/0065 toroidal, e.g. ring-shaped, doughnut-shaped
• CPC Class Codes: A61F 2230/0069 cylindrical
• CPC Class Codes: A61F 2250/0014 having different values of a given property or geometrical feature, e.g. mechanical property or material property, at different locations within the same prosthesis
• CPC Class Codes: A61L 2430/02 for reconstruction of bones; weight-bearing implants
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: C08J 2367/04 : Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 9/28 : by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A biodegradable implant for placement in nonunion bone fractures as a substitute for bone graft material is provided which is a flat plate or disk having a thickness of between about 1 mm and about 15% of the length of the bone, interconnected micropores, and canals substantially equivalent in size and spacing to naturally-occurring Haversian canals. The implant may additionally comprise additives such as growth factors, including bone morphogenic protein. In a preferred embodiment the implant is formed from a biodegradable polymer such as a polylactic acid-polyglycolic acid copolymer by a gel casting technique followed by solvent extraction to precipitate the implant as a microporous solid.

Claims

1. An implant for placement in nonunion bone fractures comprising:

a. interconnected pores having an average diameter of between about 5 μ

m and about 20 μ

m constituting a void volume of between about 40 and about 85 percent of said implant;

b. canals having a size, shape and spacing substantially corresponding to Haversian canals;

c. having a thickness of between about 1 mm and about 15% of the length of the bone;

d. having a perimeter shaped to substantially correspond to the cross-section of the ends of said nonunion bone fracture;

e. having a carvable, non-friable consistency.

2. The implant of claim 1 composed of a bioerodible polymer.

3. The implant of claim 2 composed of a bioerodible polymer comprising PLA.

4. The implant of claim 3 composed of a bioerodible polymer comprising a copolymer of PLA and PGA.

5. The implant of claim 1 having a substantially circular perimeter.

6. The implant of claim 1 also comprising a central channel therethrough having a diameter of between about 7 and about 35 mm.

7. The implant of claim 1 further comprising an additive selected from the group consisting of therapeutically active substances, degradation enhancers, degradation retardants, antibiotics, growth hormones, enzymes, immune modulators, vaccines, and medicaments.

8. The implant of claim 1 also comprising BMP.

9. The implant of claim 7 further comprising a degradation retardant which is a non-immunogenic protein having a molecular weight at least about 15,000.

10. The implant of claim 1 produced by a polymer gel casting method.

11. The implant of claim 10 comprising a PLA:

PGA copolymer having a molecular weight of between about 45,000 and about 200,000.

12. The implant of claim 10 formed by a process comprising:

a. solubilizing said polymer in an organic solvent to form a solution;

b. allowing said solution to gel in a mold to form said implant;

c. removing said gel from said mold;

d. removing said organic solvent from said gel.

13. The implant of claim 12 made by a process wherein said organic solvent is removed from said gel by means of solvent extraction.

14. The implant of claim 7 designed to release between about half and about two-thirds of said additive within the first two days of implantation in vivo and thereafter to continuously release a substantially constant amount of said additive over the degradation period of said implant.

15. A method for treating a nonunion bone fracture comprising placing into said fracture an implant comprising:

a. interconnected pores having an average diameter of between about 5 μ

m and about 20 μ

m constituting a void volume of between about 40 and about 85 percent of said implant;

b. canals having a size, shape and spacing substantially corresponding to Haversian canals;

c. having a thickness of between about 1 mm and about 15% of the length of the bone;

d. having a perimeter shaped to substantially correspond to the cross-section of the ends of said nonunion bone fracture;

e. having a carvable, non-friable consistency.

16. A method of making an implant for treating a nonunion bone fracture comprising:

a. solubilizing a biodegradable polymer precursor in an organic solvent to form a solution;

b. allowing said solution to gel in a mold comprising tines spaced to form canals in said implant having a size, shape and spacing substantially corresponding to Haversian canals;

c. removing said gel from said mold;

d. removing said organic solvent from said gel by solvent extraction whereby said polymer precipitates as a microporous solid implant having pores about 5 to about 20 μ

m and forming a void volume between about 40 and about 85 percent of said implant.

17. The method of claim 16 also comprising adding an additive selected from the group consisting of therapeutically active substances, degradation enhancers, degradation retardants, antibiotics, and growth hormones to said solution of step a. prior to allowing said solution to gel.

18. The method of claim 17 comprising rotating said mold during step b. whereby said active substance remains evenly distributed throughout said solution during gel formation.