Chouhan Dimple, Mehrotra Shreya, Majumder Omkar, Mandal Biman B
Biomaterial and Tissue Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India.
ACS Biomater Sci Eng. 2019 Jan 14;5(1):92-105. doi: 10.1021/acsbiomaterials.8b00240. Epub 2018 May 4.
Externally applied physical forces and mechanical stimulations have been found to be instructive to cells which lead to their signaling or differentiation. Further, bioreactors and functional biomaterials have been designed based on this principle to modulate cellular behavior under in vitro conditions. Herein, we have designed a magnetic actuator device (MAD) to understand the fundamental responses of two different phenomena: the effect of actuation on cardiac muscle cells and drug delivery under the influence of pulsed magnetic field. Silk fibroin (SF)-based magnetically responsive matrix, developed by incorporating magnetic iron oxide nanoparticles (IONP) within silk nanofibers was actuated with MAD. The silk matrix was seeded with cells and drugs independently to study effect of physical actuation by MAD on cellular behavior and drug release properties. Neonatal rat cardiomyocytes and H9c2 cells were used for studying the former while model drug was used to observe the latter. Pulsed magnetic stimulation promoted proliferation of cells at a significantly higher rate in comparison to those under static conditions, ≤ 0.01. For instance, a significantly higher expression of Connexin 43 gene was observed in both H9c2 and primary rat cardiomyocytes under magnetic stimulation compared to nonstimulation conditions after day 14, ≤ 0.01. A differential drug release profile corresponding to respective actuation frequency was observed while studying drug release properties. Overall, the device can be applied as a non-invasive technique to stimulate cardiac cells grown under laboratory conditions for developing functional artificial construct coupled with additional regulated drug release properties. The study thus demonstrates versatile applications of MAD in biomedical and tissue engineering.
已发现外部施加的物理力和机械刺激对细胞具有指导作用，可导致细胞信号传导或分化。此外，基于这一原理设计了生物反应器和功能性生物材料，以在体外条件下调节细胞行为。在此，我们设计了一种磁致动装置（MAD），以了解两种不同现象的基本反应：致动对心肌细胞的影响以及在脉冲磁场影响下的药物递送。通过将磁性氧化铁纳米颗粒（IONP）掺入丝素纳米纤维中开发的基于丝素蛋白（SF）的磁响应基质，用MAD进行致动。丝基质分别接种细胞和药物，以研究MAD的物理致动对细胞行为和药物释放特性的影响。新生大鼠心肌细胞和H9c2细胞用于研究前者，而模型药物用于观察后者。与静态条件下的细胞相比，脉冲磁刺激促进细胞增殖的速率显著更高，P≤0.01。例如，在第14天后，与非刺激条件相比，在磁刺激下，H9c2细胞和原代大鼠心肌细胞中连接蛋白43基因的表达均显著更高，P≤0.01。在研究药物释放特性时，观察到了与各自致动频率相对应的差异药物释放曲线。总体而言，该装置可作为一种非侵入性技术，用于刺激在实验室条件下生长的心脏细胞，以开发具有额外调节药物释放特性的功能性人工构建体。因此，该研究证明了MAD在生物医学和组织工程中的多种应用。
