Use of non-toxic crosslinking reagents to improve fatigue resistance and reduce mechanical degradation of intervertebral disc and other collagenous tissues
A method of improving the resistance of collagenous tissue to mechanical degradation in accordance with the present invention comprises the step of contacting at least a portion of a collagenous tissue with an effective amount of a crosslinking reagent. The crosslinking reagent includes a crosslinking agent such as genipin and/or proanthrocyanidin. Further, the crosslinking reagent may include a crosslinking agent in a carrier medium. The collagenous tissue to be contacted with the crosslinking reagent is preferably a portion of an intervertebral disc or articular cartilage. The contact between the tissue and the crosslinking reagent is effected by injections directly into the select tissue using a needle. Alternatively, contact between the tissue and the crosslinking reagent is effected by placement of a time-release delivery system such as a gel or ointment, or a treated membrane or patch directly into or onto the target tissue. Contact may also be effected by, for instance, soaking.
1. A method of improving the resistance of a collagenous tissue having naturally occurring cross links to mechanically-induced degradation comprising the steps of:
contacting at least a portion of a load bearing collagenous tissue within a human body with an effective amount of a crosslinking reagent comprised of a carrier medium and at least one crosslinking agent under conditions within physiologic limits to prevent tissue overheating, wherein the collagenous tissue is an intervertebral disc.
2. The method of claim 1 , wherein the at least one crosslinking agent is comprised of genipin.
3. The method of claim 1 , wherein the at least one crosslinking agent is comprised of proanthocyanidin.
4. The method of claim 1 , wherein the crosslinking agent is selected from the group consisting of genipin and proanthrocyanidin and the carrier medium is a buffered saline solution.
5. The method of claim 1 , wherein the crosslinking agent is genipin, the carrier medium is a buffered saline solution, and a concentration of the genipin in the buffered saline solution is greater than 0.033%.
6. The method of claim 1 , wherein the contact between the collagenous tissue and the crosslinking reagent is effected by injections directly into the portion of the collagenous tissue with a needle.
7. The method of claim 1 , wherein the contact between the collagenous tissue and the crosslinking reagent is effected by placement of a time-release delivery system directly into or onto the portion of the collagenous tissue.
8. The method of claim 7 , wherein the time-release delivery system is a gel or ointment.
9. The method of claim 7 , wherein the time-release delivery system is a treated membrane or patch.
10. The method of claim 7 , wherein the time-release delivery system is a treated patch.
11. The method of claim 1 , wherein the contact between the collagenous tissue and the crosslinking reagent is effected by soaking.
12. The method of claim 1 , wherein the contact between the collagenous tissue and the crosslinking reagent is effected by spraying.
13. The method of claim 1 , further comprising the step of contacting collagenous tissue adjacent to the load bearing collagenous tissue.
14. The method of claim 1 , further comprising the step of:
periodically re-contacting the portion of the collagenous tissue with an effective amount of a crosslinking reagent.