Crosslinker enhanced repair of knee meniscus
A method of treating a tear in a knee meniscus of a patient. The method includes exposing the torn knee meniscus to a protein crosslinker during surgery to repair the tear. Also provided is a fixation device for the surgical repair of tears of the meniscus of the knee, where the device contains one or more protein crosslinking reagents.
1. A method of treating a tear in a knee meniscus of a patient, comprising contacting a torn knee meniscus with a delivery device comprising a protein crosslinking agent during surgery to repair the tear, wherein the crosslinking agent increases the number of covalent crosslink bonds between native tissue proteins in the knee meniscus.
2. The method of claim 1 , wherein the delivery device comprises a patch or fixation device comprising the crosslinking agent.
3. The method of claim 2 , wherein the fixation device is an arrow, dart, tack or suture.
4. The method of claim 2 , wherein the patch or fixation device is biodegradable.
5. The method of claim 2 , wherein the patch or fixation device further comprises a basic salt.
6. The method of claim 5 , wherein the basic salt is calcium carbonate, calcium hydroxyapatite, sodium bicarbonate, 2-Amino-2-hydroxymethyl-propane-1,3-diol (Tris) or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES).
7. The method of claim 2 , wherein the patch is non-biodegradable.
8. The method of claim 2 , wherein the patch is porous and the crosslinking agent is embedded within the pores.
9. The method of claim 2 , wherein the crosslinking agent is adhered to one side of the patch as part of a semi-solid formulation.
10. The method of claim 2 , wherein the patch or fixation device is coated with one or more layers of crosslinking agent-containing biodegradable polymer.
11. The method of claim 10 , wherein each layer comprises a basic salt.
12. The method of claim 11 , wherein the salt is calcium carbonate, calcium hydroxyapatite, sodium bicarbonate, 2-Amino-2-hydroxymethyl-propane-1,3-diol (Tris) or 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES).
13. The method of claim 10 , wherein the patch or fixation device is coated with multiple layers of crosslinking agent-containing biodegradable polymer, and the crosslinking agent varies from layer to layer.
14. The method of claim 2 , wherein the patch is affixed to the meniscus with a bio-compatible adhesive.
15. The method of claim 14 , wherein the adhesive is poly(glycerol-co-sebacate acrylate), an oleic methyl ester or an alkyl ester cyanoacrylate.
16. The method of claim 2 , wherein the patch is affixed to the meniscus by an associated fixation device.
17. The method of claim 16 , wherein the associated fixation device is an arrow, dart, tack or suture.
18. The method of claim 16 , wherein the associated fixation device comprises a crosslinking agent.
19. The method of claim 1 , wherein the protein crosslinking agent is genipin, D- or L-threose, methylglyoxal, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, proanthrocyanidin, or glutaraldehyde.
20. The method of claim 13 , wherein the crosslinking agent comprises any combination of two or more compounds selected from the group consisting of genipin, D- or L-threose, methylglyoxal, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, proanthrocyanidin, and glutaraldehyde.
21. The method of claim 2 , wherein the fixation device contains about 1 to 10 mg of genipin or methylglyoxal.
22. The method of claim 2 , wherein the patch contains genipin at a level of about 1 to 250 mg.
23. The method of claim 4 , wherein the patch or fixation device contains genipin or methylglyoxal at a level of about 0.1 to 10% by weight of the polymer.
24. The method of claim 10 , wherein the one or more layers contain genipin or methylglyoxal at a level of about 0.1 to 10% by weight of the polymer.