Methods for pre-stressing and capping bioprosthetic tissue
First Claim
1. A method of treating bioprosthetic implant tissue to reduce in vivo calcification, comprising:
- at least partially cross-linking bioprosthetic implant tissue with glutaraldehyde or other aldehyde containing agents;
then stressing the cross-linked tissue by repeatedly flexing it, wherein the stressing is performed to expose potential binding sites for calcification; and
applying a calcification mitigant to the stressed, cross-linked tissue, thereby reducing in vivo calcification of the bioprosthetic implant.
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Abstract
A treatment for bioprosthetic tissue used in implants or for assembled bioprosthetic heart valves to reduce in vivo calcification is disclosed. The method includes preconditioning, pre-stressing, or pre-damaging fixed bioprosthetic tissue in a manner that mimics the damage associated with post-implant use, while, and/or subsequently applying a calcification mitigant such as a capping agent or a linking agent to the damaged tissue. The capping agent suppresses the formation of binding sites in the tissue that are exposed or generated by the damage process (service stress) and otherwise would, upon implant, attract calcium, phosphate, immunogenic factors, or other precursors to calcification. The linking agent will act as an elastic reinforcement or shock-absorbing spring element in the tissue structure at the site of damage from the pre-stressing. In one method, tissue leaflets in assembled bioprosthetic heart valves are preconditioned by simulating actual flow conditions for a predetermined number of cycles, during or after which the valve is exposed to the capping agent.
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Citations
50 Claims
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1. A method of treating bioprosthetic implant tissue to reduce in vivo calcification, comprising:
- at least partially cross-linking bioprosthetic implant tissue with glutaraldehyde or other aldehyde containing agents;
then stressing the cross-linked tissue by repeatedly flexing it, wherein the stressing is performed to expose potential binding sites for calcification; and
applying a calcification mitigant to the stressed, cross-linked tissue, thereby reducing in vivo calcification of the bioprosthetic implant. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 37)
- at least partially cross-linking bioprosthetic implant tissue with glutaraldehyde or other aldehyde containing agents;
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24. A method of treating bioprosthetic implant tissue to reduce in vivo calcification, comprising:
- cyclically stressing a glutaraldehyde or other aldehyde-fixed bioprosthetic implant tissue by repeatedly flexing it to produce additional acid binding sites until the rate of acid production in the bioprosthetic implant tissue decreases by at least 10%;
then applying a calcification mitigant to the stressed tissue, thereby reducing in vivo calcification of the bioprosthetic implant. - View Dependent Claims (25, 26, 27, 28, 29, 38, 40)
- cyclically stressing a glutaraldehyde or other aldehyde-fixed bioprosthetic implant tissue by repeatedly flexing it to produce additional acid binding sites until the rate of acid production in the bioprosthetic implant tissue decreases by at least 10%;
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30. A method of treating a bioprosthetic heart valve to reduce in vivo calcification, comprising:
- mounting a bioprosthetic heart valve comprising a pericardial tissue in a simulated fluid flow system;
subjecting the bioprosthetic heart valve to at least 100 cycles of pulsed fluid flow to cause the pericardial tissue to repeatedly flex and to produce additional acid binding sites on the pericardial tissue; and
applying a calcification mitigant to the bioprosthetic heart valve, thereby reducing in vivo calcification of the bioprosthetic heart valve. - View Dependent Claims (31, 32, 33, 34, 35, 36, 39)
- mounting a bioprosthetic heart valve comprising a pericardial tissue in a simulated fluid flow system;
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41. A method of treating a biological implant tissue to reduce in vivo calcification comprising:
- at least partially-crosslinking biological implant tissue with glutaraldehyde or other aldehyde containing agents;
stressing the biological implant tissue by subjecting the tissue to pulsed fluid flow to cause the tissue to repeatedly flex and to produce acid binding sites on the tissue; and
applying a calcification mitigant to the tissue, thereby reducing in vivo calcification of the biological implant. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50)
- at least partially-crosslinking biological implant tissue with glutaraldehyde or other aldehyde containing agents;
Specification