Engelmayr George C, Hildebrand Daniel K, Sutherland Fraser W H, Mayer John E, Sacks Michael S
Engineered Tissue Mechanics Laboratory, McGowan Institute for Regenerative Medicine, Department of Bioengineering, University of Pittsburgh, 100 Technology Drive, Room 250, Pittsburgh, PA 15219, USA.
Biomaterials. 2003 Jun;24(14):2523-32. doi: 10.1016/s0142-9612(03)00051-6.
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 2mm) 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.
动态弯曲是天然心脏瓣膜瓣叶的主要变形模式，可能会影响组织工程心脏瓣膜（TEHV）的机械和生物学发育。为了探究这一假设，开发了一种新型生物反应器，以研究动态弯曲刺激对TEHV生物材料的影响。该生物反应器用于一项研究，比较单向循环弯曲对两种候选TEHV支架有效刚度的影响：一种是聚乙醇酸（PGA）纤维的无纺布网，另一种是PGA和聚L-乳酸（PLLA）纤维的无纺布网，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个矩形样本（25×7.5×2mm）。生物反应器在至少5周的培养过程中保持无菌状态。在“弯曲时”（WF）和相反的“逆弯曲时”（AF）方向上测量有效刚度的弯曲试验表明，动态弯曲的PGA/PLLA/P4HB支架在3周时刚度比静态对照降低约72%，在5周时降低约76%（p<0.01），并且在培养3周时出现方向各向异性（AF方向更硬，p<0.01）。相比之下，动态弯曲和静态的PGA/P4HB支架在培养过程中均呈现刚度下降趋势，且未出现方向各向异性。动态弯曲的PGA/P4HB支架在3周时的刚度显著低于静态对照（p<0.05）。扫描电子显微镜显示P4HB涂层存在不均匀性和纤维破坏迹象，这可能解释了观察到的力学性能。这些结果表明，动态弯曲可使TEHV支架的力学性能产生定量和定性变化，并表明在比较机械刺激对接种细胞的TEHV构建体发育的影响时，需要考虑这些差异。
