Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance: chemical and biological mechanisms.
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 NH(3). 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.
Connolly
Jeanne M
JM
Division of Cardiology, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
Alferiev
Ivan
I
Clark-Gruel
Jocelyn N
JN
Eidelman
Naomi
N
Sacks
Michael
M
Palmatory
Elizabeth
E
Kronsteiner
Allyson
A
Defelice
Suzanne
S
Xu
Jie
J
Ohri
Rachit
R
Narula
Navneet
N
Vyavahare
Narendra
N
Levy
Robert J
RJ
D000818:Animals; D001021:Aortic Valve / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001672:Biocompatible Materials; D001696:Biomechanical Phenomena; D002114:Calcinosis / Q000517:prevention & control; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D023421:Models, Animal; D010496:Pericardium / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019736:Prostheses and Implants; D013552:Swine
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D004852:Epoxy Compounds; C516444:triglycidylamine