Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance - Chemical and biological mechanisms
Triglycidylamine crosslinking of porcine aortic valve cusps or bovine pericardium results in improved biocompatibility, biomechanics, and calcification resistance - Chemical and biological mechanisms
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DOI：
10.1016/s0002-9440(10)62227-4
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发表时间：
2005-01-01
影响因子：
6
通讯作者：
Levy, RJ
中科院分区：
文献类型：
--
作者：
Connolly, JM;Alferiev, I;Levy, RJ
我们研究了一种新型聚环氧化物交联剂，假设该交联剂在用于制备生物人工心脏瓣膜时可赋予材料稳定性和抗钙化性。通过表氯醇和NH3反应合成了三甘醇二胺（TGA）。TGA用于交联猪主动脉瓣尖、牛心包和I型胶原。对照材料与戊二醛（Glut）交联。TGA预处理材料的收缩温度与Glut固定相当。然而，TGA交联赋予比Glut预处理显著更大的胶原酶抗性，并且显著改善生物力学顺应性。羊主动脉瓣间质细胞生长在TGA预处理的胶原蛋白没有钙化，而羊主动脉瓣间质细胞生长在控制基板广泛钙化。用TGA预处理的大鼠皮下植入物（猪主动脉瓣尖/牛心包）的钙化显著低于Glut预处理的植入物。与钙化相关的细胞外基质蛋白、基质金属蛋白酶（MMP）2和9、腱生蛋白-C和骨桥蛋白的研究显示，与对照组相比，在体外和体内TGA交联下，MMP-9和腱生蛋白-C的表达均降低，而骨桥蛋白和MMP-2的表达不受影响。与Glut相比，异种移植生物材料的TGA预处理可提高稳定性，赋予生物力学性能上级于Glut交联，并显示出显著的抗钙化性。
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.