Inspired by a hitchhiking fish that uses a specialized suction organ to latch onto sharks and other marine animals, researchers from MIT and other institutions have designed a mechanical adhesive device that can attach to soft surfaces underwater or in extreme conditions, and remain there for days or weeks.
This device, the researchers showed, can adhere to the lining of the GI tract, whose mucosal layer makes it very difficult to attach any kind of sensor or drug-delivery capsule. Using their new adhesive system, the researchers showed that they could achieve automatic self-adhesion, without motors, to deliver HIV antiviral drugs or RNA to the GI tract, and they could also deploy it as a sensor for gastroesophageal reflux disease (GERD). The device can also be attached to a swimming fish to monitor aquatic environments.
The design is based on the research team's extensive studies of the remora's sucker-like disc. These discs have several unique properties that allow them to adhere tightly to a variety of hosts, including sharks, marlins, and rays. However, how remoras maintain adhesion to soft, dynamically shifting surfaces remains largely unknown.
Understanding the fundamental physics and mechanics of how this part of the fish sticks to another organism helped us to establish the underpinnings of how to engineer a synthetic adhesive system," says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women's Hospital, an associate member of the Broad Institute of MIT and Harvard, and the senior author of the study.
MIT research scientist Ziliang (Troy) Kang is the lead author of the study, which appears today in Nature. The research team also includes authors from Brigham and Women's Hospital, the Broad Institute, and Boston College.
Inspired by nature
Most protein and RNA drugs can't be taken orally because they will be broken down before they can be absorbed into the GI tract. To overcome that, Traverso's lab is working on ingestible devices that can be swallowed and then gradually release their payload over days, weeks, or even longer.
One major obstacle is that the digestive tract is lined with a slippery mucosal membrane that is constantly regenerating and is difficult for any device to stick to. Furthermore, any device that manages to attach to this lining is likely to be dislodged by food or liquids moving through the tract.
To find a solution to these challenges, the MIT team looked to the remora, also known as the sucker fish, which clings to its hosts for free transportation and access to food scraps. To explore how the remora attaches itself to dynamic, soft surfaces so strongly, Traverso's teamed up with Christopher Kenaley, an associate professor of biology at Boston College who studies remoras and other fish.
Their studies revealed that the remora's ability to stick to its host depends on a few different features. First, the large suction disc creates adhesion through pressure-based suction, just like a plunger. Additionally, each disc is divided into individual small adhesive compartments by rows of plates called lamellae wrapped in soft tissue. These compartments can independently create additional suction on nonhomogeneous soft surfaces.
There are nine species of remora, and in each one, these rows of lamellae are aligned a little bit differently - some are exclusively parallel, while others form patterns with rows tilted at different angles. These differences, the researchers found, could be the key to elucidating each species' evolutionary adaptation to its host.
Remora albescens, a unique species that exhibits mucoadhesion in the oral cavity of rays, inspired the team to develop devices with enhanced adhesion to soft surfaces with its unparallel, highly tilted lamellae orientation. Other remora species, which attach to high-speed swimmers such as marlins and swordfish, tend to have highly parallel orientations, which help the hitchhikers slide without losing adhesion as they are rapidly dragged through the water. Still other species, which have a mix of parallel and angled rows, can attach to a variety of hosts.
Tiny spines that protrude from the lamellae help to achieve additional adhesion by interlocking with the host tissue. These spines, also called spinules, are several hundred microns long and grasp onto the tissue with minimal invasiveness.
"If the compartment suction is subjected to a shear force, the friction enabled by the mechanical interlocking of the spinules can help to maintain the suction," Kang says.
Watery environments
By mimicking these anatomical features, the MIT team was able to create a device with similarly strong adhesion for a variety of applications in underwater environments.
The researchers used silicone rubber and temperature-responsive smart materials to create their adhesive device, which they call MUSAS (for "mechanical underwater soft adhesion system"). The fully passive, disc-shaped device contains rows of lamellae similar to those of the remora, and can self-adhere to the mucosal lining, leveraging GI contractions. The researchers found that for their purposes, a pattern of tilted rows was the most effective.
Within the lamellae are tiny microneedle-like structures that mimic the spinules seen in the remora. These tiny spines are made of a shape memory alloy that is activated when exposed to body temperatures, allowing the spines to interlock with each other and grasp onto the tissue surface.
The researchers showed that this device could attach to a variety of soft surfaces, even in wet or highly acidic conditions, including pig stomach tissue, nitrile gloves, and a tilapia swimming in a fish tank. Then, they tested the device for several different applications, including aquatic environmental monitoring. After adding a temperature sensor to the device, the researchers showed that they could attach the device to a fish and accurately measure water temperature as the fish swam at high speed.
To demonstrate medical applications, the researchers incorporated an impedance sensor into the device and showed that it could adhere to the esophagus in an animal model, which allowed them to monitor reflux of gastric fluid. This could offer an alternative to current sensors for GERD, which are delivered by a tube placed through the nose or mouth and pinned to the lower part of the esophagus.
They also showed that the device could be used for sustained release of two different types of therapeutics, in animal tests. First, they showed that they could integrate an HIV drug called cabotegravir into the materials that make up the device (polycaprolactone and silicone). Once adhered to the lining of the stomach, the drug gradually diffused out of the device, over a period of one week.
Cabotegravir is one of the drugs used for HIV PrEP - pre-exposure prophylaxis - as well as treatment of HIV. These treatments are usually given either as a daily pill or an injection administered every one to two months.
The researchers also created a version of the device that could be used for delivery of larger molecules such as RNA. For this kind of delivery, the researchers incorporated RNA into the microneedles of the lamellae, which could then inject them into the lining of the stomach. Using RNA encoding the gene for luciferase, a protein that emits light, the researchers showed that they could successfully deliver the gene to cells of the cheek or the esophagus.
The researchers now plan to adapt the device for delivering other types of drugs, as well as vaccines. Another possible application is using the devices for electrical stimulation , which Traverso's lab has previously shown can activate hormones that regulate appetite.
The research was funded, in part, by the Gates Foundation, MIT's Department of Mechanical Engineering, Brigham and Women's Hospital, and the Advanced Research Projects Agency for Health.
