Connolly Jeanne M, Alferiev Ivan, Clark-Gruel Jocelyn N, Eidelman Naomi, Sacks Michael, Palmatory Elizabeth, Kronsteiner Allyson, Defelice Suzanne, Xu Jie, Ohri Rachit, Narula Navneet, Vyavahare Narendra, Levy Robert J
Division of Cardiology, Children's Hospital of Philadelphia, 3615 Civic Center Blvd., Philadelphia, PA 19104, USA.
Am J Pathol. 2005 Jan;166(1):1-13. doi: 10.1016/S0002-9440(10)62227-4.
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.
我们研究了一种新型的聚环氧化物交联剂，据推测，当用于制备生物人工心脏瓣膜时，它既能使材料稳定，又具有抗钙化性能。通过环氧氯丙烷与NH(3)反应合成了三缩水甘油胺（TGA）。TGA用于交联猪主动脉瓣叶、牛心包和I型胶原。对照材料用戊二醛（Glut）交联。TGA预处理的材料的收缩温度与Glut固定相当。然而，TGA交联赋予的抗胶原酶能力明显高于Glut预处理，并且显著改善了生物力学顺应性。在TGA预处理的胶原上生长的绵羊主动脉瓣间质细胞没有钙化，而在对照基质上生长的绵羊主动脉瓣间质细胞大量钙化。对与钙化相关的细胞外基质蛋白、基质金属蛋白酶（MMPs）2和9、腱生蛋白-C和骨桥蛋白的研究表明，与对照相比，TGA交联在体外和体内均使MMP-9和腱生蛋白-C的表达降低，而骨桥蛋白和MMP-2的表达不受影响。与Glut相比, 异种移植生物材料经TGA预处理后稳定性提高，具有优于Glut交联的生物力学性能，并表现出显著的抗钙化能力。
