Method of treating a knee meniscus with a cross-linking reagent to increase resistance to tearing or rupturing
A method of treatment of native, non-denatured tissue to increase resistance to tearing, fissuring, rupturing, and/or delamination, comprising the step of: contacting at least a portion of the tissue with an effective amount of a reagent that increases crosslinks in the tissue.
1. A method of treatment of native, non-denatured, knee meniscus collagenous tissue comprising the step of:
in a patient, contacting at least a portion of the tissue with a composition comprising an effective amount of a substantially non-cytotoxic reagent that increases crosslinks in the tissue so as to increase the resistance of the knee meniscus to tearing.
2. The method of claim 1 in which there is more than one crosslinking reagent.
3. The method of claim 1 in which the reagent is non-toxic.
4. The method of claim 1 in which the composition contains one or more of the following reagents at the concentration(s) indicated below:
at least 0.001% (0.01 mg/ml) of human recombinant transglutaminase;
at least 0.01% (0.1 mg/ml) of purified animal liver transglutaminase;
at least 0.25% genipin;
at least 0.1% proanthrocyanidin;
at least 100 mM EDC;
at least 50 mM non-enzymatic agent; or
at least 0.001% lysyl oxidase.
5. The method of claim 4 in which the reagent is a non-enzymatic reagent.
6. The method of claim 5 in which the composition further comprises an oxidant, a buffer, or a combination thereof.
7. The method of claim 6 in which the oxidant is hydrogen peroxide, sodium percarbonate, sodium borate, an amino acid hydroperoxide, or perborate, and wherein the buffer is sodium bicarbonate or phosphate.
8. The method of claim 4 in which the non-enzymatic agent is one or more of the following, at the following agent concentrations:
at least 100 mM ribose;
at least 100 mM L-threose;
at least 50 mM methylglyoxal; or
at least 50 mM glyoxal.
9. The method of claim 4 in which the reagent is in a 0.1 M urea solution.
10. The method of claim 4 in which the reagent is in a substantially non-cytotoxic carrier medium.
11. The method of claim 10 in which the pH of the carrier medium is adjusted to be substantially the same as that of a healthy tissue environment.
12. The method of claim 11 in which the carrier medium is a phosphate buffered saline solution.