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(American Journal of Pathology. 2005;166:1-13.)
© 2005 American Society for Investigative Pathology

Triglycidylamine Crosslinking of Porcine Aortic Valve Cusps or Bovine Pericardium Results in Improved Biocompatibility, Biomechanics, and Calcification Resistance

Chemical and Biological Mechanisms

Jeanne M. Connolly*, Ivan Alferiev*, Jocelyn N. Clark-Gruel, Naomi Eidelman{dagger}, Michael Sacks{ddagger}, Elizabeth Palmatory*, Allyson Kronsteiner*, Suzanne DeFelice*, Jie Xu*, Rachit Ohri*, Navneet Narula§, Narendra Vyavahare* and Robert J. Levy*

From the Division of Cardiology,* The Children’s Hospital of Philadelphia, Philadelphia Pennsylvania; the Paffenbarger Research Center,{dagger} American Dental Association Foundation, National Institute of Standards and Technology, Gaithersburg, Maryland; the Department of Bioengineering,{ddagger} University of Pittsburgh, Pittsburgh, Pennsylvania; and the Department of Pathology,§ University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

We investigated a novel polyepoxide crosslinker that was hypothesized to confer both material stabilization and calcification resistance when used to prepare bioprosthetic heart valves. Triglycidylamine (TGA) was synthesized via reacting epichlorhydrin and NH3. TGA was used to crosslink porcine aortic cusps, bovine pericardium, and type I collagen. Control materials were crosslinked with glutaraldehyde (Glut). TGA-pretreated materials had shrink temperatures comparable to Glut fixation. However, TGA crosslinking conferred significantly greater collagenase resistance than Glut pretreatment, and significantly improved biomechanical compliance. Sheep aortic valve interstitial cells grown on TGA-pretreated collagen did not calcify, whereas sheep aortic valve interstitial cells grown on control substrates calcified extensively. Rat subdermal implants (porcine aortic cusps/bovine pericardium) pretreated with TGA demonstrated significantly less calcification than Glut pretreated implants. Investigations of extracellular matrix proteins associated with calcification, matrix metalloproteinases (MMPs) 2 and 9, tenascin-C, and osteopontin, revealed that MMP-9 and tenascin-C demonstrated reduced expression both in vitro and in vivo with TGA crosslinking compared to controls, whereas osteopontin and MMP-2 expression were not affected. TGA pretreatment of heterograft biomaterials results in improved stability compared to Glut, confers biomechanical properties superior to Glut crosslinking, and demonstrates significant calcification resistance.






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Copyright © 2005 by the American Society for Investigative Pathology.