Neomycin prevents enzyme-mediated glycosaminoglycan degradation in bloprosthetic heart valves
Neomycin prevents enzyme-mediated glycosaminoglycan degradation in bloprosthetic heart valves
复制标题
DOI：
10.1016/j.biomaterials.2007.02.017
复制
发表时间：
2007-06-01
期刊：
影响因子：
14
通讯作者：
Vyavahare, Naren R.
中科院分区：
文献类型：
--
作者：
Raghavan, Devanathan;Simionescu, Dan T.;Vyavahare, Naren R.
由戊二醛交联的猪主动脉瓣衍生的生物人工心脏瓣膜（BHV）经常用于心脏瓣膜置换手术。然而，BHV具有有限的耐久性，并且由于退化或钙化而失效。糖胺聚糖（GAG）是心脏瓣膜尖瓣组织的组成部分之一，不能通过常规戊二醛交联来稳定。之前我们已经证明，瓣膜GAG可以用GAG靶向化学方法进行化学固定。然而，化学稳定的GAG对酶促降解仅部分稳定。在本研究中，在瓣尖中加入酶抑制剂，以有效防止酶降解。因此，通过1-乙基-3-（3-二甲氨基丙基）碳二亚胺/N-羟基琥珀酰亚胺（EDC/NHS）化学反应，然后通过戊二醛交联（NEG），将已知的透明质酸酶抑制剂三硫酸新霉素掺入瓣尖。对照品包括使用EDC/NHS随后使用戊二醛（ENG）或仅使用戊二醛（GLUT）交联的瓣尖。与GLUT和ENG组相比，NEG组显示出对体外酶降解的抗性改善。通过差示扫描量热法（DSC）测量的热变性温度显示，所有组均显示出相似的胶原蛋白稳定性。将瓣尖皮下植入大鼠体内，以研究GAG的体内降解。NEG组保存的GAG明显多于ENG和GLUT。NEG和ENG组的钙化程度低于GLUT组。(C)2007爱思唯尔有限公司保留所有权利。
Bioprosthetic heart valves (BHVs) derived from glutaraldehyde crosslinked porcine aortic valves are frequently used in heart valve replacement surgeries. However, BHVs have limited durability and fail either due to degeneration or calcification. Glycosaminoglycans (GAGs), one of the integral components of heart valve cuspal tissue, are not stabilized by conventional glutaraldehyde crosslinking. Previously we have shown that valvular GAGs could be chemically fixed with GAG-targeted chemistry. However, chemically stabilized GAGs were only partially stable to enzymatic degradation. In the present study an enzyme inhibitor was incorporated in the cusps to effectively prevent enzymatic degradation. Thus, neomycin trisulfate, a known hyaluronidase inhibitor, was incorporated in cusps via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) chemistry followed by glutaraldehyde crosslinking (NEG). Controls included cusps crosslinked with either EDC/NHS followed by glutaraldehyde (ENG) or only with glutaraldehyde (GLUT). NEG group showed improved resistance to in vitro enzymatic degradation as compared to GLUT and ENG groups. All groups showed similar collagen stability, measured as a thermal denaturation temperature by differential scanning calorimetry (DSC). The cusps were implanted subdermally in rats to study in vivo degradation of GAGs. NEG group preserved significantly more GAGs than ENG and GLUT. NEG and ENG groups showed reduced calcification than GLUT. (C) 2007 Elsevier Ltd. All rights reserved.