Magnetic Actuator Device Assisted Modulation of Cellular Behavior and Tuning of Drug Release on Silk Platform.

Abstract

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, p ≤ 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, p ≤ 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.