Polymer incorporation into implantable biological tissue to inhibit calcification

Claim 2

A process for treating animal biological tissue prior to implantation in an animal to reduce calcification of said tissue after implantation comprising the steps of: (a) fixing said tissue under tissue fixing conditions; (b) contacting said fixed tissue with a first solution of a monomer capable of further polymerization for a time sufficient to covalently bind said monomer directly to the tissue; and (c) contacting said tissue with a second monomer solution under polymerization conditions such that said second monomer polymerizes with said first monomer bound to said tissue in an amount effective in reducing calcification of said tissue after implantation.

Claim 3

The process of claim 1 further comprising the step of removing non-covalently bound monomer from said tissue between steps (b) and (c).

Claim 4

The process of claim 1 wherein said first monomer is acrylic acid or methacrylic acid.

Claim 5

The process of claim 1 wherein said second monomer solution comprises acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide.

Claim 6

The process of claim 1 wherein said first monomer is acrylic acid or methacrylic acid, and said second monomer solution comprises acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide.

Claim 7

The process of claim 1 wherein the first monomer covalently bound to said tissue is acrylic acid, and the second monomer solution comprises acrylamide and bisacrylamide.

Claim 8

The process of claim 2 wherein the first monomer covalently bound to said tissue is acrylic acid, and the second monomer solution comprises acrylamide and bisacrylamide.

Claim 9

The process of claim 6 or 7 wherein the second monomer solution contains from about 0.5 to about 6 weight percent acrylamide.

Claim 10

The process of claim 8 wherein the second monomer solution further contains about 0.25 weight percent bisacrylamide.

Claim 11

The process of claim 1 or 2 wherein said biological tissue is tendon, ligament, heart valve, dura meter, or pericardium.

Claim 12

The process of claim 10 wherein said biological tissue is fixed with glutaraldehyde.

Claim 13

A process of treating animal biological tissue prior to implantation in an animal to reduce calcification of said tissue after implantation comprising the steps of: (a) fixing said tissue under tissue fixing conditions; (b) covalently binding a spacer to said fixed tissue; (c) contacting said fixed tissue with a first solution of a a monomer capable of further polymerization for a time sufficient to covalently bind said monomer to the spacer; and (d) contacting said tissue with a second monomer solution under polymerization conditions such that said second monomer polymerizes with said first monomer bound to said tissue through said spacer in an amount effective in reducing calcification of said tissue after implantation.

Claim 14

A process of treating animal biological tissue prior to implantation in an animal to reduce calcification of said tissue after implantation comprising the steps of: (a) fixing said tissue under tissue fixing conditions; (b) covalently binding a spacer to said fixed tissue; (c) contacting said fixed tissue with a first solution of a a monomer capable of further polymerization for a time sufficient to covalently bind said monomer to the spacer; and (d) contacting said tissue with a second monomer solution under polymerization conditions such that said second monomer polymerizes with said first monomer bound to said tissue through said spacer in an amount effective in reducing calcification of said tissue after implantation.

Claim 15

The process of claim 12 further comprising the step of removing non-covalently bound monomer from said tissue between steps (c) and (d).

Claim 16

The process of claim 12 wherein said first monomer is acrylic acid or methacrylic acid.

Claim 17

The process of claim 12 wherein said spacer is a diamine compound.

Claim 18

The process of claim 12 wherein said tissue is contacted with carbodiimide between steps (c) and (d).

Claim 19

The process of claim 12 wherein said second monomer solution comprises acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide.

Claim 20

The process of claim 12 wherein said first monomer is acrylic acid or methacrylic acid, and said second monomer solution comprises acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide.

Claim 21

The process of claim 13 wherein the first monomer covalently bound to said tissue is acrylic acid, and the second monomer solution comprises acrylamide and bisacrylamide.

Claim 22

The process of claim 17 wherein the second monomer solution contains from about 0.5 to about 6 weight percent acrylamide.

Claim 23

The process of claim 15 wherein said diamine compound has the formula R--(NH.sub.2).sub.2 wherein R is an aliphatic group having a straight, branched or cyclic chain, or an aromatic group.

Claim 24

The process of claim 20 wherein the second monomer solution further contains about 0.25 weight percent bisacrylamide.

Claim 25

The process of claim 12 or 13 wherein said biological tissue is tendon, ligament, heart valve, dura meter, or pericardium.

Claim 26

The process of claim 23 wherein said biological tissue is fixed with glutaraldehyde.

Claim 27

A process for treating animal biological tissue prior to implantation in an animal to reduce calcification of said tissue after implantation comprising the steps of: (a) fixing said tissue under tissue fixing conditions; (b) contacting said tissue with a first monomer capable of further polymerization for a time sufficient to impregnate said monomer in said tissue; and (c) contacting said tissue with a second monomer solution under polymerization conditions such that said second monomer polymerizes with said first monomer impregnated within said tissue in an amount effective in reducing calcification of said tissue after implantation.

Claim 28

A process for treating animal biological tissue prior to implantation in an animal to reduce calcification of said tissue after implantation comprising the steps of: (a) fixing said tissue under tissue fixing conditions; (b) contacting said tissue with a first monomer capable of further polymerization for a time sufficient to impregnate said monomer in said tissue; and (c) contacting said tissue with a second monomer solution under polymerization conditions such that said second monomer polymerizes with said first monomer impregnated within said tissue in an amount effective in reducing calcification of said tissue after implantation.

Claim 29

The process of claim 25 wherein said first monomer is acrylic acid or methacrylic acid.

Claim 30

The process of claim 25 or 26 wherein said second monomer solution comprises acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide.

Claim 33

The method of claim 28 wherein said first monomer is acrylic or methacrylic acid which is covalently bound to said tissue; said second monomer is acrylamide, acrylic acid, acrylic acid ester, methacrylic acid, or methacrylamide; and said tissue is fixed with glutaraldehyde.

Claim 34

The method of claim 29 wherein the biological tissue is tendon, ligament, heart valve, dura mater, or pericardium.

Claim 35

A bioprosthetic heart valve having a reduced tendency toward calcification after implantation in an animal, said heart valve comprising animal biological tissue having crosslinked hydrophilic polymers covalently immobilized thereon according to the process of claim 2 or 13.