title: Bioprosthetic tissue preservation by filling with a poly(acrylamide) hydrogel.
abstract: Glutaraldehyde (GA) fixation has been used for more than 40 years as the preferred treatment to suppress immunogenicity and increase durability of bioprosthetic tissues (BPT) used in heart valve prostheses. This fixative and its reaction products have, however, been implicated in the calcific degeneration and long-term failure of these devices. The current study investigates stabilization of BPT and the mitigation/prevention of calcification by filling aortic wall samples with a synthetic poly(acrylamide) (pAAm) hydrogel, with and without pre-treatment with GA. Histological and gravimetric analysis showed full penetration of the acrylamide (AAm) into the fresh tissue, while only partial filling could be achieved with GA pre-fixed tissue. The observed decrease in amino-group content (0.157+/-0.012-0.123+/-0.021 micromol/mg, p<0.03) and corresponding increase in shrinkage temperature (67.2+/-0.8-78.1+/-1.8 degrees C, p<0.0001) when fresh tissue was filled, indicate the participation of tissue-amines in a process that leads to BPT crosslinking. These effects were much less pronounced when the tissue was pre-fixed with GA. Filling increased the tensile stiffness of fresh tissue (to levels half that of 0.2% GA fixed tissue), but decreased the stiffness of GA pre-fixed tissue. When compared to standard 0.2% GA fixed samples, fresh tissue filled with AAm showed 88% (p<0.0001) less calcification while exhibiting similar resistance toward degradation by protease. Filling did not result in significant decreases in calcification when the tissue was pre-fixed with GA.
authors.affiliation: Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town Faculty of Health Sciences, 203 Cape Heart Centre, Anzio Road, Observatory, 7925 Cape Town, South Africa.
authors.forename: Anel
authors.initials: A
authors.lastname: Oosthuysen
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zilla
authors.forename: Paul A
authors.initials: PA
authors.lastname: Human
authors.forename: Christian A P
authors.initials: CA
authors.lastname: Schmidt
authors.forename: Deon
authors.initials: D
authors.lastname: Bezuidenhout
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000588:Amines / Q000032:analysis; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000166:cytology; D001705:Bioprosthesis; D002118:Calcium / Q000032:analysis; D005976:Glutaral / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry*; D051381:Rats; D013552:Swine; D013696:Temperature; D014021:Tissue Preservation / Q000379:methods*; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D000588:Amines; D002118:Calcium; D005976:Glutaral; D020100:Hydrogels; D000099166:Polyacrylamides