Edwards Lifesciences Corporation

Baxter International Inc.

American Hospital Supply Corporation

Sophie M Carpentier

Alain F Carpentier

Lillian J Quintero

Stefan G Schreck

Michael N Helmus

Aws S Nashef

Crystal M Cunanan

Victor S Packham

H Chris Sarner

Jong H Wang

Christine Loshbaugh

Bioprosthetic tissues are treated by immersing or otherwise contacting fixed, unfixed or partially fixed tissue with a glutaraldehyde solution that has previously been heat-treated or pH adjusted prior to its contact with the tissue. The prior heat treating or pH adjustment of the glutaraldehyde solution causes its free aldehyde concentration to decrease by about 25% or more, preferably by as much as 50%, and allows a 'stabilized' glutaraldehyde solution to be obtained at the desired concentration and pH for an optimal fixation of the tissue at high or low temperature. This treatment results in a decrease in the tissue's propensity to calcify after being implanted within the body of a human or animal patient.

Treatment of bioprosthetic tissues to mitigate post implantation calcification

Bioprosthetic tissues and methods for making same, comprising fixing bioprosthetic implant tissue by treatment with 0.1 to 10 wt. % glutaraldehyde at elevated temperature, capping said fixed tissue by treatment with a diamine crosslinking agent, and treating said capped tissue with about 0.6 wt. % glutaraldehyde.

Double cross-linkage process to enhance post-implantation bioprosthetic tissue durability

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&#xb0; 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&#xb1;2.5&#xb0; 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.

Treating biological tissues to mitigate post-implantation calcification

An apparatus for treating fixed biological tissue to inhibit calcification of the biological tissue following implantation thereof in a mammalian body. The apparatus includes a container for placing the biological tissue in contact with a treatment solution, structure to induce relative tissue/solution movement, and structure to heat the solution. The relative movement may be induced by shaking a container in which the tissue is immersed in the treatment solution, or by stirring the solution within the container. The movement may also be induced by flowing a treatment solution past the tissue to be treated. The tissue may be free to move in the treatment container, or may be restrained from gross movements. The flow may be part of a circulation system having a reservoir, with a heater being provided to heat the treatment solution in the reservoir. Alternatively, a treatment apparatus, including a fluid circulation system if desired, may be enclosed in an incubator. The tissue may be mounted in a planar configuration generally parallel to the direction of fluid flow. A flow column having a plurality of sections divided by perforated baffles may be used to treat multiple tissues at once.

Apparatuses and methods for treating biological tissue to mitigate calcification

A method of treating a biological tissue including contacting the biological tissue with an aqueous sterilizing solution, and maintaining the aqueous sterilizing solution at a temperature of about 50&#xb0; C. for a time period of about 1 to 2 days. The method of treating a biological tissue may be utilized as 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. The aqueous sterilizing solution may be glutaraldehyde of about 0.625 weight percent buffered to a pH of about 7.4.

Method for treatment of biological tissues to mitigate post-implantation calcification and thrombosis

A method for treating fixed biological tissue inhibits calcification of the biological tissue following implantation thereof in a mammalian body. The method includes placing the biological tissue in contact with glutaraldehyde and then heating the glutaraldehyde. Alternatively, methods other than heating (e.g., chemical or mechanical means), for effecting polymerization of the glutaraldehyde may also be utilized. Alternatively, the tissue may be heat treated prior to fixing thereof. Alternatively, methods other than glutaraldehyde may also be used for fixing the tissue. The biological tissue may be so treated at any time prior to implantation thereof in a mammalian body.

Methods for treating implantable biological tissues to mitigate post&#x2014;implantation calcification

Bioprosthetic tissues are treated by immersing or otherwise contacting fixed, unfixed or partially fixed tissue with a glutaraldehyde solution that has previously been heat-treated or pH adjusted prior to its contact with the tissue. The prior heat treating or pH adjustment of the glutaraldehyde solution causes its free aldehyde concentration to decrease by about 25% or more, preferably by as much as 50%, and allows a 'stabilized' glutaraldehyde solution to be obtained at the desired concentration and pH for an optimal fixation of the tissue at high or low temperature. This treatment results in a decrease in the tissue's propensity to calcify after being implanted within the body of a human or animal patient. The heat-treated or pH adjusted glutaraldehyde solution may, in some cases, also be used as a terminal sterilization solution such that the calcification-decreasing treatment with the previously treated glutaraldehyde and a terminal sterilization may be carried out simultaneously and/or in a single container.

Methods for treating implantable biological tissues to mitigate the calcification thereof and bioprosthetic articles treated by such methods

A method for fixation of biological tissues, and bioprosthetic devices prepared by such method. The method generally comprises 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 terminal sterilization.

Method for fixation of biological tissues having mitigated propensity for post-implantation calcification and thrombosis and bioprosthetic devices prepared thereby

Apparatuses for treating biological tissue to mitigate calcification

A method for treating fixed biological tissue inhibits calcification of the biological tissue following implantation thereof in a mammalian body. The method includes placing the biological tissue in contact with a treatment solution, inducing relative tissue/solution movement, and heating the solution. The relative movement may be induced by shaking a container in which the tissue is immersed in the treatment solution, or by stirring the solution within the container. The movement may also be induced by flowing a treatment solution past the tissue to be treated. The tissue may be free to move in the treatment container, or may be restrained from gross movements. The flow may be part of a circulation system having a reservoir, with a heater being provided to heat the treatment solution in the reservoir. Alternatively, a treatment apparatus, including a fluid circulation system if desired, may be enclosed in an incubator. The tissue may be mounted in a planar configuration generally parallel to the direction of fluid flow. A flow column having a plurality of sections divided by perforated baffles may be used to treat multiple tissues at once.

Methods and apparatuses for treating biological tissue to mitigate

Calcification resistant bioprosthetic implants are made from tanned biological materials, such as porcine heart valves, bovine pericardium, human dura mater or the like, which has been impregnated with a calcification-mitigating effective amount of a ferric and/or stannic salt. The impregnated biological materials and processes are particularly advantageous for the preparation of bioprosthetic heart valves. These implants have been found to be highly resistant to calcification in vivo.

Calcification mitigation of bioprosthetic implants

A process for the preparation of implantable biological tissue, and in particular bioprosthetic heart valves, which are prone to calcification after implantation. The process includes treatment of tissue with solutions prior to implantation which have been found effective in reducing calcification of the implanted tissue.

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Paris, France

Sophie M Carpentier