University of Toronto, Institute of Biomaterials and Biomedical Engineering, Faculty of Dentistry, 124 Edward Street, Toronto, Ontario, Canada M5G1G6.
Biomaterials. 2011 Jul;32(21):4816-29. doi: 10.1016/j.biomaterials.2011.03.034. Epub 2011 Apr 3.
There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) polyurethane scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering scaffolds.
几乎没有合成弹性体生物材料能够同时提供所需的生物学调节和将生物力学刺激转化为血管平滑肌细胞(VSMCs)的能力。生物力学应激是调节 VSMC 功能的重要生理因素,而聚氨酯弹性体是一类能够促进应激诱导的生物力学转化的材料。在这项研究中,将人冠状动脉平滑肌细胞(hCASMC)接种到多孔可降解极性/疏水性/离子性(D-PHI)聚氨酯支架中,然后使用定制的生物反应器在四周内对其进行单轴循环机械应变(CMS)处理。然后分析和比较支架中 hCASMC 的分布、增殖和收缩蛋白表达,以及在静态条件下生长的情况。对弹性支架施加四周的 CMS 导致 DNA 质量、细胞面积覆盖率统计学上更大,并且细胞在支架结构内更深的部位分布更好。此外,经过四周的培养,CMS 样本显示出更好的拉伸力学性能,表明在聚氨酯结构中生成了更多的细胞外基质。在整个 4 周的静态和 CMS 培养中,平滑肌α-肌动蛋白、钙调蛋白和平滑肌肌球蛋白重链的表达以及 Ki-67+细胞的缺失表明 hCASMC 在这些生物材料上保留了其收缩特性。该研究强调了在合成弹性组织工程支架的开发中实施生理相关生物力学刺激的重要性。