Treating biological tissues to mitigate post-implantation calcification
First Claim
1. A method of treating biological tissue for making a bioprosthesis which contains connective tissue protein to reduce the potential for post-implantation calcification and thrombogenicity, comprising:
- a) contacting the biological tissue with a first solution containing a surfactant and a denaturing agent selected from the group consisting of formaldehyde, ethanol, isopropanol, acetone, methyl ethyl ketone, a lower alkyl ether, a glycol, a chaotropic agent, and a highly concentrated salt solution;
b) fixing the tissue of step (a) by immersing said tissue in a buffered fixative solution containing a crosslinking agent for 0.5 hours to 14 days at 4-37°
C.;
c) contacting the fixed tissue of step (b) with more of said first solution,d) heating the tissue of step (c) in a buffered solution containing a crosslinking agent to about 50°
C.;
e) assembling a bioprosthesis by attaching any non-biological components of the prosthesis to the tissue of step (d);
f) contacting the assembled bioprosthesis of step (e) with more of said first solution, andg) sterilizing the bioprosthesis of step (f) by immersing the bioprosthesis in a sterilizing solution containing glutaraldehyde, and heating said sterilizing solution to 37.5±
2.5°
C. for a sterilizing period of time.
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Accused Products
Abstract
A method of treating a biological tissue including crosslinking with glutaraldehyde; immersing the biological tissue in a first solution containing glutaraldehyde and heat in the first solution to a temperature of about 50° C. for a first period of time; immersing the biological tissue in a second solution containing a mixture of a crosslinking agent, a denaturing agent and a surfactant; and immersing the biological tissue in a sterilizing solution containing glutaraldehyde and heating the sterilizing solution to a temperature of 37.5±2.5° C. for a sterilizing period of time. The method may include a terminal sterilization step in a method for fixation of biological tissues, and bioprosthetic devices may be prepared by such fixation method. The fixation method may include the steps of A) fixing the tissue, B) treating the tissue with a mixture of i) a denaturant, ii) a surfactant and iii) a crosslinking agent, C) fabricating or forming the bioprosthesis (e.g., forming the tissue and attaching any non-biological components thereto) and D) subjecting the bioprosthesis to the terminal sterilization method.
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Citations
9 Claims
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1. A method of treating biological tissue for making a bioprosthesis which contains connective tissue protein to reduce the potential for post-implantation calcification and thrombogenicity, comprising:
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a) contacting the biological tissue with a first solution containing a surfactant and a denaturing agent selected from the group consisting of formaldehyde, ethanol, isopropanol, acetone, methyl ethyl ketone, a lower alkyl ether, a glycol, a chaotropic agent, and a highly concentrated salt solution; b) fixing the tissue of step (a) by immersing said tissue in a buffered fixative solution containing a crosslinking agent for 0.5 hours to 14 days at 4-37°
C.;c) contacting the fixed tissue of step (b) with more of said first solution, d) heating the tissue of step (c) in a buffered solution containing a crosslinking agent to about 50°
C.;e) assembling a bioprosthesis by attaching any non-biological components of the prosthesis to the tissue of step (d); f) contacting the assembled bioprosthesis of step (e) with more of said first solution, and g) sterilizing the bioprosthesis of step (f) by immersing the bioprosthesis in a sterilizing solution containing glutaraldehyde, and heating said sterilizing solution to 37.5±
2.5°
C. for a sterilizing period of time. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
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Specification