Implantable device delivers drugs straight to the heart
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Harvard researchers have developed an implantable device that can sit directly on the heart and deliver drugs on a continual basis, to treat the after-effects of a heart attack.
This localised delivery system, shown to be effective in a 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 Ellen Roche, co-first author of the paper and former PhD student at the Harvard John A. Paulson School of Engineering and Applied Sciences.
“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 localised, replenishable treatment regimen at various pathological sites.”
The device, dubbed 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.
In experiments, the researchers used the device to deliver cardiac regenerative therapy. After a heart attack, residual scarring and tissue remodelling can occur and may ultimately lead to heart failure.
Different therapies, including drugs, proteins and stem cells, could treat scarring, but these treatments struggle to stay at their intended target, often require multiple doses and could lead to toxic side effects.
Stem cells are one of the most promising avenues of treatment for cardiac scarring, but so far clinical trials have shown only modest benefits, in part because there is no reliable method to deliver multiple doses of stem cells without multiple surgeries.
The researchers demonstrated that Therepi can increase heart function after injury for up to four weeks when stem cells are repeatedly delivered to the reservoir.
“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.”
Before moving onto clinical implementation, the researchers will focus on optimising 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.