The active tissue adhesive activates the mechanical sensor and prevents muscle atrophy

Muscles are depleted due to lack of exercise, just as severed limbs immobilized in a cast are quickly depleted, and more slowly
in older people.
Clinicians refer to this phenomenon as muscle wasting, and it is also a debilitating symptom in people with neurological disorders such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), and may also be a systemic response to
a variety of other diseases, including cancer and diabetes.

Mechanical therapy, a form of treatment performed by manual or mechanical means, is considered to have broad potential
in tissue repair.
The most famous example is massage, which relaxes muscles
by compressing them.
However, whether stretching and contracting muscles by external means can also be used as a treatment is less clear
.
So far, two major challenges have hindered such research: the limited mechanical system that does not produce stretching and contracting forces evenly along the length of the muscle, and the inefficient delivery of these mechanical stimuli to the surface and deep layers of muscle tissue
.

Now, bioengineers have developed a mechanically active adhesive called MAGENTA, which functions as a soft robotic device to solve this double problem
.
IN ANIMAL MODELS, MAGENTA SUCCESSFULLY PREVENTS AND SUPPORTS THE RECOVERY
OF MUSCLE WASTING.
The team's findings were published in Natural Materials.

"With MAGENTA, we have developed a new integrated multi-component system for mechanical stimulation of muscles that can be placed directly on muscle tissue to trigger key molecular pathways
for growth.
" Senior author and Wyss founding core faculty member David Mooney, Ph.
D.
, said: "While this study is the first to demonstrate that externally provided stretching and contractile motion can prevent atrophy in animal models, we believe that the core design of the device can be broadly applicable to a variety of disease settings where atrophy is a major concern
.
" Mooney leads the Wyss Institute's Immune Materials Platform and is the Robert P.
Pinkas Family Professor
in the School of Bioengineering.

An adhesive that makes muscles move

One of the main components of MAGENTA is an engineered spring made of Nitinol, a metal known as a "shape memory alloy" (SMA) that allows MAGENTA to drive
quickly when heated to a certain temperature.
The researchers drove the spring by connecting it to a microprocessor unit that allows programming the frequency and duration of the stretch and contraction cycles
.
Other components of MAGENTA are the elastomer matrix that makes up the body of the device and insulates the SMA from heat, and the "ductile binder"
that keeps the device firmly attached to the muscle tissue.
In this way, the device aligns with the natural axis of muscle movement, transferring the mechanical force generated by the SMA deep into the
muscle.
Mooney's team is advancing MAGENTA, which stands for "Mechanoactive Gel Elastomer-Nitinol Tissue Binder," as one of several ductile gel adhesives that are functional for a variety of regenerative applications
across multiple tissues.

AFTER DESIGNING AND ASSEMBLING THE MAGENTA DEVICE, THE TEAM FIRST TESTED ITS MUSCULAR DEFORMATION POTENTIAL IN ISOLATED MUSCLES AND THEN IMPLANTED IT IN
ONE OF THE MICE'S MAIN CALF MUSCLES.
The device did not cause any serious signs of tissue inflammation and damage and showed a mechanical tension of about 15% of the muscles, consistent with
natural deformation during exercise.

Next, to evaluate its therapeutic effects, the researchers built a model
of muscle wasting by immobilizing the hindlimbs of mice in a small, mold-like shell for up to two weeks after implantation of a MAGENTA device in a living organism.
Lead author and Wyss Technology Development Researcher said: "During this time, untreated muscles and muscles treated with devices but not significantly stimulated were emaciated, while muscles that were actively stimulated were
emaciated.
" Our method can also promote the recovery of muscle mass lost during the three-week immobilization period and induce activation of major biochemical mechanotransduction pathways known to induce protein synthesis and muscle growth
.
”

Several aspects of mechanical therapy

Mooney's team, with the team of Connor Walsh, an associate professor at Weiss, found that using different soft robotic devices, regulating periodic compression (rather than stretching and contraction) of acutely injured muscles reduced inflammation and made muscle fiber repair possible
in acutely injured muscles.
In their new study, Mooney's team asked whether these compressive forces also prevented muscle wasting
.
HOWEVER, WHEN THEY DIRECTLY COMPARED MUSCLE COMPRESSION THROUGH THE FORMER DEVICE FOR MUSCLE STRETCHING AND CONTRACTION THROUGH THE MAGENTA DEVICE, ONLY THE LATTER HAD A CLEAR THERAPEUTIC EFFECT
ON THE MOUSE ATROPHY MODEL.
"Using a unique soft robotic approach that has a unique effect on muscle tissue, it is very likely that specific mechanical treatment pathways
for disease or injury will open up," Mooney said.

To further expand the possibilities of MAGENTA, the team explored whether SMA springs could also be laser-actuated, something never shown before, which would make the method essentially wireless, expanding its therapeutic use.

IN FACT, THEY DEMONSTRATED THAT THE IMPLANTED MAGENTA DEVICE DOES NOT REQUIRE ANY WIRES AND ACTS AS A LIGHT-RESPONSE DRIVER THAT CAN DEFORM
MUSCLE TISSUE WHEN THE LASER SHINES THROUGH THE SKIN LAYER ABOVE.
Although the laser drive cannot reach the same frequency as the electric drive, and adipose tissue in particular seems to absorb some of the laser, the researchers believe that the device's light sensitivity and performance could be further improved
.
"The general function of MAGENTA and the fact that its assembly can easily be expanded from millimeters to a few centimeters make it an interesting central component of future mechanotherapy, not only to treat atrophy, but potentially also to accelerate the regeneration
of the skin, heart, and other places that might benefit from this form of mechanical conduction," Nam said.

"The growing recognition that mechanical therapies can address critical unmet needs in regenerative medicine that drug-based therapies simply cannot achieve has spurred a new area of research that connects robotic innovation with human physiology to the level
of molecular pathways that deliver different mechanical stimuli," said the Wyss founder.
This study by Dave Mooney and his team is a very elegant and forward-looking example of how this type of mechanical therapy could be used in the clinic in the
future.
Ingebel is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and the Hansjörg Wyss Professor of Biomotivational Engineering in the Ocean.

The study's other authors are Bo Ri Seo, Alexander Najibi and Stephanie McNamara
from the Weiss Institute and SEAS Mooney's team 。 The study was supported
by grants from the National Institute of Dental and Craniofacial Research (award # R01DE013349), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (award # P2CHD086843), and the National Science Foundation Center for Materials Research Science and Engineering (award # DMR14-20570).

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Antibiotic combinations reduce Staphylococcus aureus clearance