New bionic-engineered testbeds provide insight into human cell responses to cardiac ablation and other medical device interventions.
By Brenda Ogle, University of Minnesota
Our lab is changing the approach to testing cardiac ablation tools with bionic testbeds.
In collaboration with Medtronic and the lab of Michael McAlpine, we have developed bionic testbeds that consist of living cardiac tissues large enough to test clinical-grade devices.
In 2015, our lab developed an integrated biomaterial platform that statistically identified an extracellular matrix formulation best supportive of cardiomyocyte differentiation. Soon thereafter we established a method to 3D bioprint the extracellular matrix formulation with human stem cells in a bioink.
Human-induced pluripotent stem cells in the bioprinted structure could proliferate to high densities and then differentiate into cardiac muscle in the 3D constructs, creating bionic-engineered centimeter-scale human cardiac tissue large enough to accommodate medical devices. Because the engineered tissues are living, the impact of the device following intervention can be tracked for several months.
This diagram from Brenda Ogle’s lab shows the bioprinting of stem cells in a chambered construct and the subsequent differentiation and maturation of such structures. [Image courtesy of the Ogle Research Group]
Paving new paths in cardiac ablation therapy
Recently, we specifically explored the case of cardiac ablation therapy through left atrial pulmonary vein ablation. Through our previous methods, we developed bionic-engineered testbeds and collaborated with Medtronic to test their cryoablation tip.
The lab of Michael McAlpine added flexible sensors to our engineered tissue, utilizing electrical impedance tomography to enable the real-time spatiotemporal mapping of pressure distribution. Through this, we could track the temperature — and pressure — that the device was applying to the tissue.
We found a close correlation between the cell response to ablation and the applied pressure. Under some conditions, cardiomyocytes could survive in the ablated region with more rounded morphology compared to the unablated controls, and connectivity was disrupted. This is the first known functional characterization of living human cardiomyocytes following an ablation procedure that suggests several mechanisms by which arrhythmia might redevelop following an ablation.
These bionic-engineered testbeds can be indicators of tissue health and function and provide unique insight into human cell responses to ablative interventions. Studies like these could accelerate the development of more efficient therapies for cardiac arrhythmias, including atrial fibrillation.
This diagram from Brenda Ogle’s lab shows the bionic myocardial testbed with pressure-sensing capability. [Image courtesy of the Ogle Research Group]
The future of bionic testbeds
We plan to use the living tissue platform to optimize cardiac ablation parameters to ensure healthy cardiac function over time.
There are several aspects of fabrication in how bionic testbeds are currently tested: handling stem cells, driving differentiation of pure cardiomyocyte populations, and bioprinting and assembly of the tissue. Several labs are building up this technology, and with our publications, those labs will soon be able to make structures large enough to test clinical-grade devices.
There are opportunities for industry to collaborate with us, especially within the space of evaluating human cardiac cells with clinical-grade medical devices. Our bionic testbeds can track the mechanical function of cardiac cells over time and after intervention because the testbed is living.
We are interested in collaborating to evaluate other types of cardiac medical devices, including cardiac pacemakers as an adjacent approach or replacement to existing preclinical models. If you’d like to explore a partnership, please get in touch by emailing me at ogle@umn.edu.
Brenda Ogle [Photo courtesy of the University of Minnesota]
Special thanks to University of Minnesota Institute for Engineering in Medicine Communications Associate Aithanh Nguyen for her help on this contribution.
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The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Medical Design & Outsourcing or its employees.
