Cardiovascular Engineering
Electrical Fields Modulate Endothelialization of Cardiovascular Therapeutic Devices – AnElectroceutical Strategy for Enhanced Hemocompatibility
Kaitlyn R. Ammann
Senior Research Scientist
University of Arizona, United States
Togzhan Spatayeva
Student
University of Arizona
Tucson, Arizona, United States
Marvin J. Slepian
Regents Professor
University of Arizona, United States
Background/Purpose: Thrombosis of blood-implanted cardiovascular therapeutic devices such as stents, valves and ventricular assist devices remains a major limitation leading to thromboembolic events including device malfunction, stroke and potential death. Current clinical strategies to limit thrombosis have been only partially effective, with recent pharmacologic mechanistic studies revealing that most anti-thrombotic drugs in clinical use today have limited ability to limit shear-mediated platelet activation and thrombosis. Here, we utilize a new drug-free approach in an attempt to enhance thromboresistance via facilitated endothelial cell coverage of foreign biomaterial surfaces. We hypothesized that local application of DC electric fields (DCEF) – i.e. galvanotaxis, will direct and enhance endothelial cell (ECs) migration and surface coverage. In this study, we aim to define parameters of DCEFs as they relate to the directed growth of vascular ECs.
Methods: A galvanotaxis chamber was specifically designed for exposing ECs to DCEFs. Saline solution and agar salt bridges mediated DCEF exposure to cell media and ECs. Prior to DCEF application, human umbilical vein endothelial cells (HUVECs) were seeded at 3 x 104 cells/ml for 4 hours in the chamber. DCEFs were then applied to the saline solution over a range of electric potentials (0 – 150 mV/cm). Time-lapse imaging was utilized to track cell movement over time (4 hours).
Results: Vascular ECs were found to be responsive to galvanotaxis, with both migration directionality (i.e. alignment to the DCEFs) and cell displacement. Notably, an increase in DCEF magnitude led to a significant increase in EC displacement and increased directionality towards the cathode.
Conclusion: Our findings suggest galvanotaxis may serve as an electroceutical alternative to drugs, facilitating and enhancing cell-based anti-thrombotic protection of implanted cardiovascular therapeutic devices blood-contacting surfaces. Follow-on studies are underway aimed at further translation of this approach to a practical method to implanted cardiovascular device hemocompatibility.