A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials

A novel bioreactor for the dynamic flexural stimulation of tissue engineered heart valve biomaterials
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DOI:
10.1016/s0142-9612(03)00051-6
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发表时间:
2003-06-01
期刊:
影响因子:
14
通讯作者:
Sacks, MS
Sacks, MS
中科院分区:
工程技术1区
文献类型:
--
作者:
Engelmayr, GC;Hildebrand, DK;Sacks, MS

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动态弯曲是天然心脏瓣膜尖部变形的主要模式,并且可能影响组织工程心脏瓣膜(TEHV)的机械和生物发育。为了探索这一假设,开发了一种新型生物反应器来研究动态弯曲刺激对 TEHV 生物材料的影响。它在一项研究中实施,以比较单向循环弯曲对两种候选 TEHV 支架有效刚度的影响:聚乙醇酸 (PGA) 纤维无纺网,以及 PGA 和聚 L-乳酸 (PLLA) 纤维无纺网,两者均涂有聚 4-羟基丁酸酯 (P4HB)。该生物反应器能够在细胞培养箱的无菌条件下动态弯曲 12 个矩形样品 (25 x 7.5 x 2 mm)。生物反应器中保持无菌状态至少5周的培养时间。测量“有弯曲”(WF)和相反“反对弯曲”(AF)方向有效刚度的弯曲测试表明,动态弯曲的 PGA/PLLA/P4HB 支架比静态对照支架的刚度大约低 72%(3 周)和 76%(5 周)(p < 0.01),并且它们在孵化 3 周时出现方向各向异性(更硬的 AF,p < 0.01)。相比之下,动态弯曲和静态 PGA/P4HB 支架都表现出随着孵化而刚度降低的趋势,但没有出现方向各向异性。 3 周时,动态弯曲的 PGA/P4HB 支架的硬度明显低于静态对照(p < 0.05)。扫描电子显微镜显示出异质 P4HB 涂层和纤维断裂的迹象,这对观察到的机械性能提出了可能的解释。这些结果表明动态弯曲可以使 TEHV 支架的机械性能产生定量和定性的变化,并表明在比较机械刺激对细胞接种的 TEHV 结构发育的影响时需要考虑这些差异。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
Dynamic flexure is a major mode of deformation in the native heart valve cusp, and may effect the mechanical and biological development of tissue engineered heart valves (TEHV). To explore this hypothesis, a novel bioreactor was developed to study the effect of dynamic flexural stimulation on TEHV biomaterials. It was implemented in a study to compare the effect of uni-directional cyclic flexure on the effective stiffness of two candidate TEHV scaffolds: a non-woven mesh of polyglycolic acid (PGA) fibers, and a non-woven mesh of PGA and Poly L-lactic acid (PLLA) fibers, both coated with poly 4-hydroxybutyrate (P4HB). The bioreactor has the capacity to dynamically flex 12 rectangular samples (25 x 7.5 x 2 mm) under sterile conditions in a cell culture incubator. Sterility was maintained in the bioreactor for at least 5 weeks of incubation. Flexure tests to measure the effective stiffness in the "with-flexure" (WF) and opposing "against-flexure" (AF) directions indicated that dynamically flexed PGA/PLLA/P4HB scaffolds were approximately 72% (3 weeks) and 76% (5 weeks) less stiff than static controls (p < 0.01), and that they developed directional anisotropy by 3 weeks of incubation (stiffer AF, p < 0.01). In contrast, both dynamically flexed and static PGA/P4HB scaffolds exhibited a trend of decreased stiffness with incubation, with no development of directional anisotropy. Dynamically flexed PGA/ P4HB scaffolds were significantly less stiff than static controls at 3 weeks (p < 0.05). Scanning electron microscopy revealed signs of heterogeneous P4HB coating and fiber disruption, suggesting possible explanations for the observed mechanical properties. These results indicate that dynamic flexure can produce quantitative and qualitative changes in the mechanical properties of TEHV scaffolds, and suggest that these differences need to be accounted for when comparing the effects of mechanical stimulation on the development of cell-seeded TEHV constructs. (C) 2003 Elsevier Science Ltd. All rights reserved.