Cummings Christopher L, Gawlitta Debby, Nerem Robert M, Stegemann Jan P
Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Biomaterials. 2004 Aug;25(17):3699-706. doi: 10.1016/j.biomaterials.2003.10.073.
Vascular constructs were formed by embedding rat aortic smooth muscle cells in three-dimensional matrices of Type I collagen, fibrin, or a mixture of collagen and fibrin in a 1:1 ratio, at total matrix protein concentrations of 2 and 4 mg/ml. Morphological and mechanical properties were evaluated after 6 days in culture, and the effect of cyclic mechanical strain on collagen-fibrin mixture constructs was also studied. Constructs made with the lower protein concentration compacted to the greatest degree, and fibrin was found to enhance gel compaction. Each matrix type exhibited a characteristic stress-strain profile. Pure collagen had the highest linear modulus and pure fibrin had the lowest. The ultimate tensile stress was strongly dependent on the degree of gel compaction, and collagen-fibrin mixtures at 2mg/ml total protein content exhibited the highest values. Application of cyclic mechanical strain to collagen-fibrin mixture constructs caused a significant increase in gel compaction and a decrease in cell proliferation. The linear modulus, ultimate tensile stress and toughness of the constructs were all augmented by mechanical strain. These results demonstrate that the properties of engineered vascular tissues can be modulated by the combination of selected extracellular matrix components, and the application of mechanical stimulation.
通过将大鼠主动脉平滑肌细胞嵌入I型胶原蛋白、纤维蛋白或胶原蛋白与纤维蛋白1:1比例的混合物的三维基质中,总基质蛋白浓度为2mg/ml和4mg/ml,形成血管构建体。培养6天后评估形态学和力学性能,并研究循环机械应变对胶原-纤维蛋白混合物构建体的影响。蛋白质浓度较低的构建体压实程度最大,发现纤维蛋白可增强凝胶压实。每种基质类型都表现出特征性的应力-应变曲线。纯胶原蛋白的线性模量最高,纯纤维蛋白的最低。极限拉伸应力强烈依赖于凝胶压实程度,总蛋白含量为2mg/ml的胶原-纤维蛋白混合物表现出最高值。对胶原-纤维蛋白混合物构建体施加循环机械应变导致凝胶压实显著增加,细胞增殖减少。构建体的线性模量、极限拉伸应力和韧性均因机械应变而增强。这些结果表明,工程化血管组织的性能可通过选择的细胞外基质成分组合以及机械刺激的应用来调节。