Use of hydrogels to fix bone replacements

• US 5,645,592 A
• Filed: 04/27/1995
• Issued: 07/08/1997
• Est. Priority Date: 05/20/1992
• Status: Expired due to Term

• Current Assignee: M.U.R.S.T.
• Original Assignee: Murst Italian Ministry For Universities and Scientific and Technological Research
• Inventors: Netti, Paolo Antonio, Nicolais, Luigi, Ambrosio, Luigi, Callegaro, Lanfranco
• Primary Examiner(s): Prebilic, Paul B.
• Application Number:
  US08/341,541
• Time in Patent Office: 803 Days
• Field of Search: 623/16, 606/63, 606/66, 606/68, 606/71, 606/70, 606/76, 604/266
• US Class Current: 606/63
• CPC Class Codes: A61B 17/58 for osteosynthesis, e.g. bone plates, screws , setting implements or the like A61B17/14, A61B17/16 take precedence
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/127 containing fillers of phosphorus-containing inorganic materials
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08L 33/10 Homopolymers or copolymers of methacrylic acid esters
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

Provided are orthopedic fasteners and replacements such as nails, screws, pins, hip and knee replacements, etc., coated with hydrogels and other biocompatible/biodegradable materials which expand in the presence of liquids. Swelling of such coatings causes the fastener or replacement to be securely fixed into position once inserted into bone material. Useful coating materials include methacrylates, hyaluronic acid esters, and crosslinked esters of hyaluronic acid resulting from the esterification of hyaluronic acid with polyhydric alcohols. Also provided is a method for fixing a bone or bone replacement in position employing such coated orthopedic fasteners or replacements.

Claims

1. An orthopedic fastener or replacement, covered with a second coating comprising a hydrogel or other biocompatible, biodegradable material which expands in the presence of a liquid, wherein said hydrogel or other biocompatible, biodegradable material is a member selected from the group consisting of polyhydroxyethylmethacrylate, a semi-interpenetrating polymer network composed of crosslinked poly(2-hydroxyethylmethacrylate) and poly(caprolactone), a copolymer of 2-hydroxyethylmethacrylate and methylmethacrylate, poly(2-hydroxyethylmethacrylate), a hyaluronic acid ester, and a crosslinked ester of hyaluronic acid resulting from the esterification of hyaluronic acid with polyhydric alcohols;

and

wherein said fastener or replacement is first coated with a first coating of a non-swelling polymer possessing groups chemically and/or physically related to those of said hydrogel or said biocompatible, biodegradable material before coating said fastener or replacement with either said hydrogel or said biocompatible, biodegradable material.

2. The orthopedic fastener or replacement of claim 1, wherein said fastener or replacement is in the form selected from the group consisting of a nail, a screw, a pin, a hip replacement, a knee replacement, and an angle replacement.

3. The orthopedic fastener or replacement of claim 1, wherein said hydrogel or other biocompatible, biodegradable material possesses hydrophilic and hydrophobic groups in its polymeric network.

4. The orthopedic fastener or replacement of claim 1, wherein said fastener or replacement is made of stainless steel, a metal alloy, titanium, or cobalt-chromium.

5. The orthopedic fastener or replacement of claim 1, wherein said second coating is formed from a crosslinked material and wherein the degree of crosslinking of said second coating is controlled by the temperature at which polymerization is conducted.

6. The orthopedic fastener or replacement of claim 1, wherein unreacted monomers are removed from said second coating by immersing the coated fastener or replacement in water.

7. The orthopedic fastener or replacement of claim 1, wherein said poly(2-hydroxyethylmethacrylate) and said poly(caprolactone) are present in said second coating in a ratio of 90:

10, w/w.

8. The orthopedic fastener or replacement of claim 1, wherein the mechanical performance of said crosslinked poly(2-hydroxyethylmethacrylate) and said poly(caprolactone) in said second coating is varied by varying the amount of poly(caprolactone) in the mixture.

9. The orthopedic fastener or replacement of claim 1, wherein said 2-hydroxyethylmethacrylate and said methylmethacrylate are present in said second coating in a ratio of 50:

50, w/w.

10. The orthopedic fastener or replacement of claim 1, wherein the second coating has a thickness in the range of from about 0.5 mm to 2 mm.

11. The orthopedic fastener or replacement of claim 1, wherein said hydrogel or other biocompatible, biodegradable material in said second coating further comprises a rigid organic or inorganic filler.

12. The orthopedic fastener or replacement of claim 11, wherein said rigid inorganic filler is a member selected from the group consisting of glass beads and hydroxyapatite crystals.

13. The orthopedic fastener or replacement of claim 1, wherein said poly(2-hydroxyethylmethacrylate) further comprises glass bead composites.

14. The orthopedic fastener or replacement of claim 1, wherein said non-swelling polymer is linear polymethylmethacrylate.

15. The orthopedic fastener or replacement of claim 1, wherein said hydrogel or other biocompatible, biodegradable material is impregnated with at least one pharmacologically active substance.

16. The orthopedic fastener or replacement of claim 15, wherein said pharmacologically active substance is at least one member selected from the group consisting of an antibiotic, an antiviral agent, an anti-infective agent, an antibacterial agent, and a disinfectant.

17. The orthopedic fastener or replacement of claim 16, wherein said antibiotic is at least one member selected from the group consisting of an aminoglucoside, a macrolide, a tetracycline, and a peptide.

18. The orthopedic fastener or replacement of claim 16, wherein said antibiotic is at least one member selected from the group consisting of gentamicin, neomycin, streptomycin, dihydrostreptomycin, kanamycin, amikacin, tobramycin, spectinomycin, erythromycin, aureomycin, oleandomycin, carbomycin, spiramycin, oxytetracycline, rolitetracycline, bacitracin, polymyxin B, gramicidin, colistin, chloramphenicol, thiamphenicol, lincomycin, vancomycin, novobiocin, ristocetin, clindamycin, amphotericin B, griseofulvin, nystatin, and a physiologically acceptable salt thereof.

19. The orthophedic fastener or replacement of claim 16, wherein said antiviral agent is at least one member selected from the group consisting of iododeoxyuridine, adenine arabinoside, trifluorothymidine, acyclovir, ethyldeoxyuridine, bromovinyldeoxyuridine, and 5-iodo-5'"'"'-amino-2'"'"', 5'"'"'-dideoxyuridine.

20. The orthopedic fastener or replacement of claim 16, wherein said anti-infective agent is at least one member selected from the group consisting of diethylcarbamazine, mebendazole, and a sulfamide.

21. The orthopedic fastener or replacement of claim 16, wherein said antibacterial is at least one member selected from the group consisting of nitrofurazone, mafenids, chlorhexidine, and a derivative of 8-hydroxyquinoline.

22. The orthopedic fastener or replacement of claim 1, wherein said hyaluronic acid ester is at least one member selected from the group consisting of the partial propyl ester of hyaluronic acid (HY) having 50% esterified carboxylic groups, and 50% sodium salified carboxylic groups;

the partial isopropyl ester of HY having 50% esterified carboxylic groups, and 50% sodium salified carboxylic groups;

the partial ethyl ester of HY having 75% esterified carboxylic groups, and 25% sodium salified carboxylic groups;

the partial methyl ester of HY having 75% esterified carboxylic groups, and 25% sodium salified carboxylic groups;

the methyl ester of HY;

the ethyl ester of HY;

the propyl ester of HY;

the partial butyl ester of HY having 50% esterified carboxylic groups, and 50% sodium salified carboxylic groups;

the partial ethoxycarbonylmethyl ester of HY having 75% esterified carboxylic groups, and 25% sodium salified carboxylic groups the n-pentyl ester of HY;

the isopentyl ester of HY;

the benzyl ester of HY;

the β

-phenylethyl ester of HY;

the benzyl ester of HY;

the partial propyl ester of HY having 85% esterified carboxylic groups, and 15% sodium salified carboxylic groups the n-octyl ester of HY;

the isopropyl ester of HY;

the 2,6-dichlorobenzyl ester of HY;

the 4-[terbutylbenzyl] tertbutylbenzyl ester of HY;

the heptadecyl ester of HY;

the octadecyl ester of HY;

the 3-phenylpropyl ester of HY;

the 3,4,5-trimethoxybenzyl ester of HY;

the cinnamyl ester of HY;

the decyl ester of HY; and

the nonyl ester of HY.

23. The orthopedic fastener or replacement of claim 1, wherein said crosslinked ester of hyaluronic acid is at least one member selected from the group consisting of the crosslinked esters listed in the following Table

26. The orthopedic fastener or replacement of claim 1, wherein said fastener or replacement is in the form selected from the group consisting of an intramedullar nail, a spiral screw, and an intracortical screw.

24. A method for fixing a bone or bone replacement in position, comprising the steps of:

(a) providing a hole in existing bone to accommodate a fastener;

(b) locating a bone or bone replacement adjacent to said existing bone, said bone or bone replacement having a hole therein to accommodate a fastener;

(c) providing an orthopedic fastener or replacement, covered with a second coating comprising a hydrogel or other biocompatible, biodegradable material which expands in the presence of a liquid, wherein said hydrogel or other biocompatible, biodegradable material is a member selected from the group consisting of polyhydroxyethylmethacrylate, a semi-interpenetrating polymer network composed of crosslinked poly(2-hydroxyethylmethacrylate) and poly(caprolactone), a copolymer of 2-hydroxyethylmethacrylate and methylmethacrylate, poly(2-hydroxyethylmethacrylate), a hyaluronic acid ester, and a crosslinked ester of hyaluronic acid resulting from the esterification of hyaluronic acid with polyhydric alcohols; and

wherein said fastener or replacement is first coated with a first coating of a non-swelling polymer possessing groups chemically and/or physically related to those of said hydrogel or said biocompatible, biodegradable material before coating said fastener or replacement with either said hydrogel or said biocompatible, biodegradable material; and

(d) inserting said fastener of step (c) into the holes in said existing bone and said bone or bone replacement such that said coating absorbs fluid and swells, thereby securely fixing said bone or bone replacement in position.

25. The method of claim 24, wherein the secure fixing of step (d) is accomplished by the swelling of said coating to fill gaps between said fastener and said existing bone, and between said fastener and said bone or bone replacement.