“Therepi” goes straight to the heart

“Therepi”can deliver drugs, proteins and stem cells directly to a diseased heart .
(c) Second Bay Studio/Harvard SEAS

What if drugs and other therapies to treat diseased or scarred tissues could be repeatedly delivered directly to their targets without the need for multiple procedures? Now, an international team of researchers have demonstrated a new, implantable device that can sit directly on the heart and deliver drugs on a continual basis to treat the aftereffects of a heart attack.

“After a heart attack we could use this device to deliver therapy to prevent a patient from getting heart failure. If the patient already has some degree of heart failure, we can use the device to attenuate the progression,” explains Ellen Roche, co-first author of the study and assistant professor at MIT’s Department of Mechanical Engineering and Institute for Medical Engineering and Science.

“Therepi” looks like a small patch and can be sutured onto tissue, in this case, a heart. The patch contains a sponge-like biomaterial that holds and releases therapies through its permeable surface. The biomaterial can be connected to a port or pump via a tube when it needs to be refilled. The permeable surface, made of a porous polycarbonate membrane, can be tuned for different size molecules and interchanged for smaller or larger pore sizes depending on what is being delivered and how quickly it should be released.

The device has shown to be effective in an in vivo pre-clinical study, could improve the efficiency of drugs, requiring lower doses, and reduce adverse side effects for therapies that are currently delivered systemically. “This proof-of-concept study demonstrates that our device can repeatedly deliver drugs and increase retention of cells in proximity to the heart to increase heart function,” said Roche. “For us, this is only the beginning of multiple ongoing studies that will use this system as a platform for therapy delivery to diseased tissue, and as a research tool to understand the effects of a localized, replenishable treatment regimen at various pathological sites.”

Localized therapies

Two of the most common systems currently used for delivering therapies to prevent heart failure are inefficient and invasive. In one method, drugs are delivered systemically rather than being administered directly to the site of the damage. The volume of drugs used has to be limited to avoid toxic side effects and often only a small amount reaches the damaged heart tissue. “From a pharmacological point-of-view, it’s a big problem that you’re injecting something that doesn’t stay at the damaged tissue long enough to make a difference,” says William Whyte, co-first author and PhD candidate at Trinity College Dublin and AMBER.

The alternative method involves an invasive procedure to directly inject therapies into the heart muscle. Since multiple doses are needed, this requires multiple invasive surgeries. “Therepi” addresses the problems with current drug delivery methods by administering localized, non-invasive therapies as many times as needed. “The material we used to construct the reservoir was crucial. We needed it to act like a sponge so it could retain the therapy exactly where you need it,” adds Whyte. “That is difficult to accomplish since the heart is constantly squeezing and moving.”

Therepi’s reservoir is placed on a dime for size reference and connected to a self-sealing subcutaneous port.
(c) Whyte, et al./Nature Biomedical Engineering

That’s where Therepi comes in. “The stem cells remain in the reservoir and act as production factories, constantly releasing factors that are transported out of the device and modulate healing,” said Roche. “With multiple replenishments, the ’dose’ of these factors is increased, as is their potential to elicit a functional benefit. At 28 days, we observed, among other cardiac parameters, an increased ejection fraction, meaning the percentage of blood ejected compared to total volume of chamber increased.” The hearts that received multiple dosages of cells via therapy had more cardiac function than those who received only a single injection or no treatment at all.

Therepi’s capabilities go beyond treating heart disease. Since it provides the opportunity for multiple, localized doses to be delivered, it could be used as a tool to identify the exact dosage appropriate for a host of conditions. “We are hoping to use the device itself as a research tool to learn more about the optimal drug loading regime,” says Roche.

For the first time, researchers could have an opportunity to track multiple refills of localized therapies over time to help identify the best dosing intervals and dose amount. “As a pharmacist by training, I’m really excited to start investigating what the best dose is, when is the best time to deliver after a heart attack, and how many doses are needed to achieve the desired therapeutic effect,” adds Whyte.

More possibilities

Before moving onto clinical implementation, the researchers will focus on optimizing the design of the device for a variety of potential therapies that can be delivered with this system. The team is also exploring the potential to combine this approach with past work on soft robotic extra-cardiac assistive devices, to create a multifaceted mechanical and therapeutic approach to heart disease. “The device is really a platform that can be tailored to different organ systems and different conditions,” says Claudia Varela, a PhD student in the Harvard-MIT Division of Health Sciences and Technology. “It’s just a great example of how intersectional research looking at both devices and biological therapies can help us come up with new ways to treat disease.”

“Practically, this platform will allow us to conduct tightly controlled studies to find optimal dosing and timing regimens for regenerative cardiac therapies,” said Roche. “Until now, these studies have been challenging due to the invasiveness of multiple procedures. This type of device could be applied to treatment options for multiple disease states including other types of heart disease, diabetes and cancer.”

Sources: Massachusetts Institute of Technology and Harvard University