Shah Sagar R, Vyavahare Naren R
Cardiovascular Implant Research Laboratory, Department of Bioengineering, Clemson University, 401 Rhodes Engineering Research Center, Clemson, SC 29634, USA.
Biomaterials. 2008 Apr;29(11):1645-53. doi: 10.1016/j.biomaterials.2007.12.009. Epub 2008 Jan 15.
Bioprosthetic valves are used in thousands of heart valve replacement surgeries. Existing glutaraldehyde-crosslinked bioprosthetic valves fail due to either calcification or degeneration. Glutaraldehyde crosslinking does not stabilize valvular glycosaminoglycans (GAGs). GAGs, predominantly present in the medial spongiosa layer of native heart valve cusps, play an important role in regulating physico-mechanical behavior of the native cuspal tissue during dynamic motion. The primary objective of this study was to identify the role of cuspal GAGs in valve tissue buckling. Glutaraldehyde-crosslinked cusps showed extensive buckling compared to fresh, native cusps. Removal of GAGs by treatment with GAG-degrading enzymes led to a marked increase in buckling behavior in glutaraldehyde-crosslinked cusps. We demonstrate that the retention of valvular GAGs by carbodiimide crosslinking together with chemical attachment of neomycin trisulfate (a hyaluronidase inhibitor), prior to glutaraldehyde crosslinking, reduces the extent of buckling in bioprosthetic heart valves. Furthermore, following exposure to GAG-digestive enzymes, neomycin-trisulfate-bound cusps experienced no alterations in buckling behavior. Such moderate buckling patterns mimicked that of fresh, untreated cusps subjected to similar bending curvatures. Thus, GAG stabilization may subsequently improve the durability of these bioprostheses.
生物人工心脏瓣膜被应用于数千例心脏瓣膜置换手术中。现有的戊二醛交联生物人工心脏瓣膜会因钙化或退化而失效。戊二醛交联无法稳定瓣膜糖胺聚糖（GAGs）。GAGs主要存在于天然心脏瓣膜尖的内侧海绵层，在动态运动过程中对调节天然瓣膜尖组织的物理力学行为起着重要作用。本研究的主要目的是确定瓣膜尖GAGs在瓣膜组织屈曲中的作用。与新鲜的天然瓣膜尖相比，戊二醛交联的瓣膜尖表现出广泛的屈曲。用GAG降解酶处理去除GAGs会导致戊二醛交联瓣膜尖的屈曲行为显著增加。我们证明，在戊二醛交联之前，通过碳二亚胺交联保留瓣膜GAGs并化学连接新霉素三硫酸盐（一种透明质酸酶抑制剂），可减少生物人工心脏瓣膜的屈曲程度。此外，在暴露于GAG消化酶后，结合新霉素三硫酸盐的瓣膜尖的屈曲行为没有改变。这种适度的屈曲模式类似于新鲜的、未处理的瓣膜尖在类似弯曲曲率下的屈曲模式。因此，GAG的稳定化可能随后提高这些生物假体的耐久性。
