Hogan Matthew, Chen Yi-Ting, Kolhatkar Arati G, Candelari Christopher J, Madala Sridhar, Lee T Randall, Birla Ravi
Department of Biomedical Engineering, Science and Engineering Research Center (SERC-Building 545), University of Houston, 3605 Cullen Boulevard, Room 2027, Houston, Texas 77204-5060, United States.
Department of Chemistry, Science and Engineering Research Center (SERC-Building 545), University of Houston, 3605 Cullen Boulevard, Room 5004, Houston, Texas 77204-5060, United States.
ACS Biomater Sci Eng. 2016 Sep 12;2(9):1619-1629. doi: 10.1021/acsbiomaterials.6b00375. Epub 2016 Sep 1.
Bioreactor systems, an integral component of tissue engineering, are designed to simulate complex in vivo conditions to impart functionality to artificial tissue. All standard forms of stretch bioreactors require physical contact with artificial heart muscle (AHM). However, we believe that noncontact stretch bioreactors have the potential to lead to higher functional benefit of AHM. Our work is focused on the fabrication of a noncontact magnetic stretch bioreactor (MSB) that uses magnetic nanoparticles to simulate stretch conditions to impart functionality. During our development of this system, we applied magnetically induced stretch conditioning through application of an oscillating magnetic field to a ferromagnetic heart muscle model. Fibrin scaffolds were loaded with magnetic nanoparticles prior to tissue model formation. Oscillating magnetic fields were applied by a novel bioreactor system through displacement of a neodymium magnet. The addition of commercially obtained iron(III) oxide (FeO) in sufficient quantities to allow for physiologically relevant stretches (15% axial displacement) caused toxic effects after 4 days of culture. In contrast, loading scaffolds with monodispersed, high-saturation-magnetization magnetite (FeO) nanoparticles specifically prepared for these experiments increased the field strength of the magnetized fibrin 10-fold over polydispersed, low-saturation magnetization, FeO. Additionally, loading with FeO enabled magnetically actuated stretching with markedly reduced toxicity over 8 days of culture. Using a 20% stretch 0.5 Hz protocol, we observed a significant increase in twitch force over controls at days 4 and 6. This work provides a technology for controlled noncontact mechanical stretch to condition AHM.
生物反应器系统是组织工程的一个重要组成部分，旨在模拟复杂的体内条件，赋予人工组织功能。所有标准形式的拉伸生物反应器都需要与人工心肌（AHM）进行物理接触。然而，我们认为非接触式拉伸生物反应器有可能为AHM带来更高的功能效益。我们的工作重点是制造一种非接触式磁拉伸生物反应器（MSB），该反应器使用磁性纳米颗粒来模拟拉伸条件以赋予功能。在我们开发这个系统的过程中，我们通过向铁磁心肌模型施加振荡磁场来应用磁诱导拉伸调节。在组织模型形成之前，将磁性纳米颗粒加载到纤维蛋白支架中。通过一个新型生物反应器系统通过钕磁铁的位移来施加振荡磁场。添加足够量的市售氧化铁（FeO）以实现生理相关的拉伸（15%轴向位移），在培养4天后会产生毒性作用。相比之下，用专门为这些实验制备的单分散、高饱和磁化率的磁铁矿（Fe₃O₄）纳米颗粒加载支架，使磁化纤维蛋白的场强比多分散、低饱和磁化率的FeO提高了10倍。此外，加载Fe₃O₄能够在8天的培养过程中以明显降低的毒性进行磁驱动拉伸。使用20%拉伸、0.5赫兹的方案，我们在第4天和第6天观察到抽搐力比对照组有显著增加。这项工作提供了一种用于控制非接触机械拉伸以调节AHM的技术。
