Raghavan Devanathan, Starcher Barry C, Vyavahare Naren R
Cardiovascular Implant Research Laboratory (CIRL), Department of Bioengineering, Clemson University, 501 Rhodes Hall, Clemson, SC 29634, USA.
Acta Biomater. 2009 May;5(4):983-92. doi: 10.1016/j.actbio.2008.11.004. Epub 2008 Nov 27.
Bioprosthetic heart valve (BHV) cusps have a complex architecture consisting of an anisotropic arrangement of collagen, glycosaminoglycans (GAGs) and elastin. Glutaraldehyde (GLUT) is used as a fixative for all clinical BHV implants; however, it only stabilizes the collagen component of the tissue, and other components such as GAGs and elastin are lost from the tissue during processing, storage or after implantation. We have shown previously that the effectiveness of the chemical crosslinking can be increased by incorporating neomycin trisulfate, a hyaluronidase inhibitor, to prevent the enzyme-mediated GAG degradation. In the present study, we optimized carbodiimide-based GAG-targeted chemistry to incorporate neomycin into BHV cusps prior to conventional GLUT crosslinking. This crosslinking leads to enhanced preservation of GAGs during in vitro cyclic fatigue and storage. The neomycin group showed greater GAG retention after both 10 and 50 million accelerated fatigue cycles and after 1 year of storage in GLUT solution. Thus, additional binding of neomycin to the cusps prior to standard GLUT crosslinking could enhance tissue stability and thus heart valve durability.
生物人工心脏瓣膜（BHV）瓣叶具有复杂的结构，由胶原蛋白、糖胺聚糖（GAGs）和弹性蛋白的各向异性排列组成。戊二醛（GLUT）用作所有临床BHV植入物的固定剂；然而，它仅能稳定组织中的胶原蛋白成分，而其他成分如GAGs和弹性蛋白在处理、储存或植入后会从组织中流失。我们之前已经表明，通过加入硫酸新霉素（一种透明质酸酶抑制剂）来防止酶介导的GAG降解，可以提高化学交联的效果。在本研究中，我们优化了基于碳二亚胺的靶向GAG化学方法，以便在传统的GLUT交联之前将新霉素掺入BHV瓣叶中。这种交联导致在体外循环疲劳和储存过程中GAGs的保留增强。新霉素组在经历100万次和5000万次加速疲劳循环后以及在GLUT溶液中储存1年后，GAG保留量更高。因此，在标准GLUT交联之前将新霉素额外结合到瓣叶上可以增强组织稳定性，从而提高心脏瓣膜的耐久性。
