PDF(Pubmed)
Abstract：
The number of patients with valvular heart disease is increasing yearly, and valve replacement is the most effective treatment, during which bioprosthetic heart valves (BHVs) are the most widely used. Commercial BHVs are mainly prepared with glutaraldehyde (Glut) cross-linked bovine pericardial or porcine aortic valves, but the residual free aldehyde groups in these tissues can cause calcification and cytotoxicity. Moreover, insufficient glycosaminoglycans (GAGs) in tissues can further reduce biocompatibility and durability. However, the anti-calcification performance and biocompatibility might be improved by blocking the free aldehyde groups and increasing the GAGs content in Glut-crosslinked tissues. In our study, adipic dihydrazide (ADH) was used to neutralize the residual free aldehyde groups in tissues and provide sites to blind with oligohyaluronan (OHA) to increase the content of GAGs in tissues. The modified bovine pericardium was evaluated for its content of residual aldehyde groups, the amount of OHA loaded, physical/chemical characteristics, biomechanical properties, biocompatibility, and in vivo anticalcification assay and endothelialization effects in juvenile Sprague-Dawley rats. The results showed that ADH could completely neutralize the free aldehyde groups in the Glut-crosslinked bovine pericardium, the amount of OHA loaded increased and the cytotoxicity was reduced. Moreover, the in vivo results also showed that the level of calcification and inflammatory response in the modified pericardial tissue was significantly reduced in a rat subcutaneous implantation model, and the results from the rat abdominal aorta vascular patch repair model further demonstrated the improved capability of the modified pericardial tissues for endothelialization. Furthermore, more α-SMA+ smooth muscle cells and fewer CD68+ macrophages infiltrated in the neointima of the modified pericardial patch. In summary, blocking free-aldehydes and loading OHA improved the anti-calcification, anti-inflammation and endothelialization properties of Glut-crosslinked BHVs and in particularly, this modified strategy may be a promising candidate for the next-generation of BHVs.
摘要：
心脏瓣膜病的患者人数逐年增加,瓣膜置换是最有效的治疗方法,在此期间，生物人工心脏瓣膜（BHV）是最广泛使用。商业BHV主要用戊二醛（Glut）交联的牛心包或猪主动脉瓣制备，但这些组织中残留的游离醛基可引起钙化和细胞毒性。此外，组织中糖胺聚糖(GAG)不足可进一步降低生物相容性和耐久性。然而,可以通过阻断游离醛基和增加Glut交联组织中的GAG含量来改善抗钙化性能和生物相容性。在我们的研究中,己二酸二酰肼（ADH）用于中和组织中残留的游离醛基，并为低聚透明质酸（OHA）提供盲点，以增加组织中GAG的含量。评价了改性牛心包膜的残留醛基含量,OHA的加载量，物理/化学特性，生物力学特性，生物相容性，以及幼年Sprague-Dawley大鼠的体内抗钙化测定和内皮化作用。结果表明,ADH能完全中和Glut交联牛心包膜中的游离醛基,OHA的负载量增加，细胞毒性降低。此外，体内结果还表明，在大鼠皮下植入模型中，改良心包组织的钙化和炎症反应水平显着降低，大鼠腹主动脉血管补片修复模型的结果进一步证明了改良心包组织的内皮化能力。此外，更多的α-SMA+平滑肌细胞和更少的CD68+巨噬细胞浸润在改良心包补片的新内膜中。总之,阻断游离醛和负载OHA改善了抗钙化，Glut交联的BHV的抗炎和内皮化特性，特别是，这种改进的策略可能是下一代BHV的有希望的候选方案。
