Yao Lan, Liu Jinyu, Andreadis Stelios T
Bioengineering Laboratory, Department of Chemical and Biological Engineering, State University of New York at Buffalo, Amherst, NY 14260, USA.
Pharm Res. 2008 May;25(5):1212-21. doi: 10.1007/s11095-007-9499-6. Epub 2007 Dec 19.
We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical properties of fibrin-based TEV and examine the relationship between mechanical strength and smooth muscle cell (SMC) function.
To this end, we prepared TEV that were composed of two layers: a cellular layer containing SMC embedded in fibrin hydrogel to provide contractility and matrix remodeling; and a second cell-free fibrin layer composed of high concentration fibrinogen to provide mechanical strength.
The ultimate tensile force of double-layered TEV increased with FBG concentration in the cell-free layer in a dose-dependent manner. Double-layered TEV exhibited burst pressure that was ten-fold higher than single-layered tissues but vascular reactivity remained high even though the cells were constricting an additional tissue layer.
These results showed that mechanical strength results largely from the biomaterial but contractility requires active cellular machinery. Consequently, they may suggest novel approaches for engineering biomaterials that satisfy the requirement for high mechanical strength while preserving SMC function.
我们最近证明,基于纤维蛋白的组织工程血管(TEV)表现出血管反应性、基质重塑以及足够的强度,可植入绵羊动物模型的静脉中,并在其中保持通畅15周。在此,我们提出一种方法来改善基于纤维蛋白的TEV的机械性能,并研究机械强度与平滑肌细胞(SMC)功能之间的关系。
为此,我们制备了由两层组成的TEV:一层是细胞层,包含嵌入纤维蛋白水凝胶中的SMC,以提供收缩性和基质重塑;另一层是无细胞纤维蛋白层,由高浓度纤维蛋白原组成,以提供机械强度。
双层TEV的极限拉伸力随着无细胞层中纤维蛋白原浓度的增加而呈剂量依赖性增加。双层TEV的爆破压力比单层组织高十倍,尽管细胞收缩了额外的组织层,但血管反应性仍然很高。
这些结果表明,机械强度主要源于生物材料,但收缩性需要活跃的细胞机制。因此,它们可能为设计满足高机械强度要求同时保留SMC功能的生物材料提出新方法。