Girardot J M, Girardot M N
Biomedical Design, Inc., Atlanta, GA 30318, USA.
J Heart Valve Dis. 1996 Sep;5(5):518-25.
A new fixation method for bioprosthetic tissues is being developed, which does not utilize the standard glutaraldehyde treatment. This method, referred to as Ultifix, uses a coupler and a coupling enhancer with or without one or more coupling agents. It fixes the tissue by linking the amine and the carboxyl moieties through amide bonds either directly, or indirectly when coupling agents form bridges. The amide bonds thus formed are more stable than the Schiff-base bonds formed by glutaraldehyde. All compounds used during the fixation process and their by-products are water-soluble, and are easily removed by washing. In addition, the by-products are not toxic, as opposed to glutaraldehyde, which induces toxic reactions after implantation. The tests described in the manuscript were specifically aimed at evaluating the cross-linking efficacy of the process on heart valve tissues, as well as their resistance to calcification in the rat model.
Porcine aortic roots and porcine pericardium were fixed using the coupling agents 1,6-hexane diamine (DIA) and suberic acid (SUA) in the presence of the coupler 1-ethyl-3(-3 dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and the coupling enhancer N-hydroxysulfosuccinimide (sulfo-NHS). The tissues were then evaluated for their resistance to thermal denaturation, to enzymatic digestion, and to calcification when implanted subdermally in rats for two, four, eight and 16 weeks.
The results demonstrate that the cusps and the wall of porcine aortic roots, and porcine pericardium, are as well stabilized and as cross-linked by Ultifix as they are by the standard glutaraldehyde method. In addition, the cusps of the porcine aortic root and the porcine pericardium, but not the wall of the porcine aortic root, calcify minimally and significantly less when implanted subdermally for up to 16 weeks in three week old rats than the control material fixed with glutaraldehyde.
The Ultifix process of cross-linking bioprosthetic heart valves may thus be a good alternative to the standard glutaraldehyde process of fixation, with increased durability and without toxic effects.
正在研发一种用于生物假体组织的新型固定方法，该方法不采用标准的戊二醛处理。这种方法称为Ultifix，使用一种偶联剂和一种偶联增强剂，可搭配或不搭配一种或多种偶联剂。它通过酰胺键直接或在偶联剂形成桥梁时间接连接胺基和羧基部分来固定组织。由此形成的酰胺键比戊二醛形成的席夫碱键更稳定。固定过程中使用的所有化合物及其副产物均为水溶性，易于通过洗涤去除。此外，与戊二醛不同，副产物无毒，戊二醛在植入后会引发毒性反应。手稿中描述的测试专门旨在评估该过程对心脏瓣膜组织的交联效果，以及它们在大鼠模型中的抗钙化能力。
在偶联剂1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐（EDC）和偶联增强剂N-羟基磺基琥珀酰亚胺（磺基-NHS）存在的情况下，使用偶联剂1,6-己二胺（DIA）和辛二酸（SUA）固定猪主动脉根部和猪心包。然后评估这些组织在皮下植入大鼠2周、4周、8周和16周时对热变性、酶消化和钙化的抵抗力。
结果表明，猪主动脉根部的瓣叶和壁以及猪心包，通过Ultifix固定和交联的程度与标准戊二醛方法相同。此外，在三周龄大鼠皮下植入长达16周时，猪主动脉根部的瓣叶和猪心包，但不包括猪主动脉根部的壁，钙化程度极低且明显低于用戊二醛固定的对照材料。
因此，生物假体心脏瓣膜的Ultifix交联过程可能是标准戊二醛固定过程的一个很好的替代方法，具有更高的耐久性且无毒性作用。
