Alison Marsden, PhD
Pediatrics and Bioengineering
A team of researchers at Stanford is working on a unique idea to develop a device to induce ventricular growth by applying mechanical stimuli to single ventricle (SV) patients' heart tissue. The idea is the mechanical force would drive a favorable growth in the heart tissue to regrow or salvage whatever tissue exists of the second ventricle and towards a functional cure for SV heart defects.
“The current clinical paradigm assumes that you are stuck with one ventricle, and you have to prolong the life of that ventricle for as long as possible,” says Alison Marsden, PhD, Associate Professor in the Departments of Pediatrics and Bioengineering at the Stanford School of Medicine. “We started thinking about ways to salvage or regrow the second ventricle.”
Other fields have demonstrated this is possible, explains Dr. Marsden. Similar to bone lengthening in orthopedics, a mechanical force is applied to the bone and directs the bone structure to grow in the desired direction. Inspired by this, why couldn't the research team design a similar type of device for the heart to do that, she says.
To address this idea, Dr. Marsden is leading a multi-disciplinary team with expertise in cardiovascular mechanics, medical device design, pediatric cardiovascular surgery, and congenital heart disease. The MCHRI awarded $250,000 to Dr. Marsden in 2020 through the Additional Ventures Innovation Fund Single Ventricle Disease Research Awards Program for her project to develop this mechanical device to stimulate ventricular growth in SV patients.
The co-investigators on the project are Ellen Kuhl, PhD, Professor and Chair of Mechanical Engineering, Mark Cutkosky, PhD, Professor of Mechanical Engineering, and Daniel Bernstein, MD, Professor of Pediatric Cardiology.
What has happened
Current treatment for SV patients focuses on maintaining the health and performance of the one ventricle. The general course for SV patients is to undergo three stages of open-heart surgeries, with the goal at each procedure to redirect the blood flow properly. The last phase, the Fontan circulation, eventually enables blood flow from the lower body to the lungs.
“Most of the prior clinical and research directions in treating single ventricle patients have been focused on how we make the most of the one ventricle in the system,” says Dr. Marsden. When the performance of that ventricle fails, patients will often need a transplant, she explains. The team wanted to shift this thinking and look in a different direction on whether you could regrow or salvage the existing ventricle via a mechanical device.
During the first six months into the project, Dr. Marsden and her team worked with Dr. Cutkosky and the design team in the Department of Mechanical Engineering to prototype the device. The team has developed several prototypes and considered ventricle function, growth mechanism, and mechanical force when applied to a model heart.
Dr. Marsden’s lab is also looking at computational models of the heart to refine the device's design further. “We start with a model of the ventricle, apply forces in different locations, and try to optimize the placement of those forces the device is exerting,” she says.
Recognizing there are challenges associated with implementing this device in small patients during complex surgeries, Dr. Marsden and her team are focused on developing a short-term device that can be applied over time as the babies are growing. The project is currently in iterative phases between the models and prototypes.
“These projects are high-risk, high-reward type of [research] that would be very hard to fund through NIH or other traditional mechanisms,” says Dr. Marsden. “We’re grateful to the funders [Additional Ventures and MCHRI] for willing to take a chance on this project.”
For the rest of the project period, Dr. Marsden and her team will refine the prototype devices and ultimately apply them to a testing environment. The hope is that the device would stimulate desirable growth in the SV and potentially restore bi-ventricle circulation.
The project is currently in progress. This story is a complimentary piece to a larger article. To read the article, click here.
BY ROXANNA VAN NORMAN
Roxanna Van Norman is the marketing manager for the Stanford Maternal and Child Health Research Institute.