Multi-step connective tissue stabilization method and stabilized tissue formed thereby
First Claim
1. A method for stabilizing ex vivo or in vitro a cardiac/heart valve connective tissue comprising:
- a first step including contacting the ex vivo or in vitro connective tissue with a neomycin trisulfate salt, the connective tissue including collagen, elastin, and one or more glycosaminoglycans;
a second step carried out subsequent to the first step, the second step including contacting the ex vivo or in vitro connective tissue with a solution comprising a first carbodiimide crosslinking reagent and pentagalloylglucose;
a third step carried out subsequent to the second step, the third step including contacting the ex vivo or in vitro connective tissue with a second carbodiimide crosslinking reagent.
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Abstract
A multi-step stabilization method for connective tissue is described. Stabilized tissues can exhibit increased resistance to degradation due to enzyme activity, fatigue and storage. The multi-step method includes a first step during which the tissue can be incubated with a glycosaminoglycanase inhibitor such as a sulfated oligosaccharide, one example of which being neomycin, a second step during which the tissue can be incubated with a crosslink activator such as a carbodiimide crosslink activator and/or a crosslinking agent such as a heterobifunctional crosslinking agent and/or a phenolic compound such as a tannin, examples of which include tannic acid and pentagalloylglucose, and a third step during which the tissue can be incubated with a second crosslink activator that can be the same or different as the first crosslink activator.
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Citations
18 Claims
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1. A method for stabilizing ex vivo or in vitro a cardiac/heart valve connective tissue comprising:
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a first step including contacting the ex vivo or in vitro connective tissue with a neomycin trisulfate salt, the connective tissue including collagen, elastin, and one or more glycosaminoglycans; a second step carried out subsequent to the first step, the second step including contacting the ex vivo or in vitro connective tissue with a solution comprising a first carbodiimide crosslinking reagent and pentagalloylglucose; a third step carried out subsequent to the second step, the third step including contacting the ex vivo or in vitro connective tissue with a second carbodiimide crosslinking reagent. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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- 14. A stabilized ex vivo or in vitro connective heart valve tissue comprising a neomycin trisulfate salt and a pentagalloylglucose.
Specification