用于心脏瓣膜组织工程的生物功能化醋酸纤维素纳米支架的研制

E. Chainoglou, V. Karagkiozaki, T. Choli-Papadopoulou, Charisios Mavromanolis, A. Laskarakis, S. Logothetidis
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引用次数: 12

摘要

目前使用的机械和生物心脏瓣膜假体具有令人满意的短期性能,但可能在长期表现出几个主要的缺点。基于碳、金属和聚合物成分的机械假体需要永久性抗凝治疗,并且它们的使用经常导致不良反应,例如血栓栓塞并发症和心内膜炎。近年来,人们需要一种能够生长、修复和重塑的心脏瓣膜假体。组织工程的概念为这种装置的发展提供了良好的前景。理想的支架应该模仿天然细胞外基质(ECM)结构中发现的材料的结构和用途。本研究的目的是开发用于瓣膜组织再生的醋酸纤维素支架(CA)。在对其进行彻底的物理化学和生物学表征后,进行生物功能化处理以增加细胞增殖。特别是,支架表面被功能分子扩增,如RGD肽(Arg-Gly-Asp)和YIGSRG laminins(酪氨酸-异亮氨酸-甘氨酸-丝氨酸-精氨酸-甘氨酸),这些功能分子通过生物素-链亲和素键固定,这是自然界中最强的非共价键。最后一步是成功地用CA生物功能纳米支架覆盖主动脉金属瓣膜,并培养细胞,以创建与天然瓣膜相当的解剖结构。基于ca的纳米支架已经取得了令人满意的结果。我们发现,细胞在具有生物功能的瓣膜表面成功生长,从而形成类似于天然组织的支架,并与RGD肽和层粘连蛋白等生物活性因子相结合,不仅使瓣膜表面具有生物相容性,而且可以促进心脏瓣膜的内皮化,从而产生抗凝血作用
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Development of Biofunctionalized Cellulose Acetate Nanoscaffolds for Heart Valve Tissue Engineering
Currently-used mechanical and biological heart valve prostheses have a satisfactory short-term performance, but may exhibit several major drawbacks on the long-term. Mechanical prostheses, based on carbon, metallic and polymeric components, require permanent anticoagulation treatment, and their usage often leads to adverse reactions, e.g. thromboembolic complications and endocarditis. In recent years, there is a need for a heart valve prosthesis that can grow, repair and remodel. The concept of tissue engineering offers good prospects into the development of such a device. An ideal scaffold should mimic the structural and purposeful profile of materials found in the natural extracellular matrix (ECM) architecture. The goal of this study was to develop cellulose acetate scaffolds (CA) for valve tissue regeneration. After their thorough physicochemical and biological characterization, a biofunctionalization process was made to increase the cell proliferation. Especially, the surface of scaffolds was amplified with functional molecules, such as RGD peptides (Arg-Gly-Asp) and YIGSRG laminins (Tyrosine-Isoleucine-Glycine-Serine-Arginine-Glycine) which immobilized through biotin-streptavidin bond, the strongest non-covalent bond in nature. Last step was to successfully coat an aortic metallic valve with CA biofunctionallized nanoscaffolds and cultivate cells in order to create an anatomical structure comparable to the native valve. Promising results have been obtained with CA-based nanoscaffolds. We found that cells grown successfully on the biofunctionalized valve surface thereby scaffolds that resemble the native tissues, elaborated with bioactive factors such as RGD peptides and laminins not only make the valve’s surface biocompatible but also they could promote endothyliazation of cardiac valves causing an anti-coagulant effect
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