In a previous research study, Mooneys group in partnership with Wyss Associate Faculty member Conor Walshs group found that regulated cyclical compression (as opposed to extending and contraction) of acutely hurt muscles, utilizing a different soft robotic gadget, decreased inflammation and allowed the repair of muscle fibers in acutely injured muscle. When they directly compared muscle compression by means of the previous device to muscle stretching and contraction by means of the MAGENTA gadget, just the latter had clear healing effects in the mouse atrophy model.
Muscle atrophy is the squandering or loss of muscle mass and strength. Massage, which utilizes compressive stimulation to relax muscles, is the most popular kind of mechanotherapy, however, it is not clear whether extending and contracting muscles through external methods can likewise be reliable as a treatment. There have actually been two significant obstacles to studying this possibility: a lack of mechanical systems that can equally use stretching and contraction forces to muscles along their whole length, and the inefficient shipment of these mechanical stimuli to the surface area and deeper layers of muscle tissue.
This image reveals examples of MAGENTA models produced with a “shape memory alloy” spring and an elastomer, and how their sizes compare to that of a one-cent coin. Credit: Wyss Institute at Harvard University
Now, bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have established a mechanically active adhesive named MAGENTA, which functions as a soft robotic device and fixes this two-fold issue. In an animal design, MAGENTA successfully prevented and supported the healing from muscle atrophy. The teams findings are released in Nature Materials.
” With MAGENTA, we developed a brand-new integrated multi-component system for the mechanostimulation of muscle that can be directly put on muscle tissue to set off crucial molecular pathways for growth,” stated senior author and Wyss Founding Core Faculty member David Mooney, Ph.D. “While the research study supplies first proof-of-concept that externally offered stretching and contraction motions can avoid atrophy in an animal design, we think that the gadgets core design can be broadly adjusted to different disease settings where atrophy is a major issue.” Mooney leads the Wyss Institutes Immuno-Materials Platform and is likewise the Robert P. Pinkas Family Professor of Bioengineering at SEAS.
An adhesive that can make muscles move
Among MAGENTAs major components is a crafted spring made from nitinol, a kind of metal called “shape memory alloy” (SMA) that enables MAGENTAs fast actuation when heated to a specific temperature level. The scientists activated the spring by electrically electrical wiring it to a microprocessor unit that allows the frequency and duration of the extending and contraction cycles to be programmed. The other components of MAGENTA are an elastomer matrix that forms the body of the gadget and insulates the heated SMA, and a “difficult adhesive” that makes it possible for the gadget to be securely complied with muscle tissue.
In this way, the gadget is lined up with the natural axis of muscle motion, transferring the mechanical force created by SMA deep into the muscle. Mooneys group is advancing MAGENTA, which stands for “mechanically active gel-elastomer-nitinol tissue adhesive,” as one of numerous Tough Gel Adhesives with functionalities tailored to numerous regenerative applications throughout numerous tissues.
After assembling the magenta and designing gadget, the team evaluated its muscle-deforming potential, initially in isolated muscles ex vivo and then by implanting it on among the significant calf muscles of mice. The gadget did not cause any serious indications of tissue inflammation and damage and displayed a mechanical pressure of about 15% on muscles, which matches their natural deformation during exercise.
Next, to assess its healing efficacy, the researchers utilized an in vivo model of muscle atrophy by debilitating a mouses hind limb in a small cast-like enclosure for up to two weeks after implanting the MAGENTA device on it. “While unattended muscles and muscles treated with the device but not promoted considerably squandered away throughout this period, the actively promoted muscles revealed minimized muscle wasting,” said first-author and Wyss Technology Development Fellow Sungmin Nam, Ph.D. “Our approach might likewise promote the recovery of muscle mass that already had been lost over a three-week duration of immobilization, and cause the activation of the significant biochemical mechanotransduction paths understood to generate protein synthesis and muscle development.”
Elements of mechanotherapy
In a previous research study, Mooneys group in partnership with Wyss Associate Faculty member Conor Walshs group discovered that managed cyclical compression (instead of extending and contraction) of acutely hurt muscles, using a various soft robotic device, lowered swelling and made it possible for the repair of muscle fibers in acutely hurt muscle. In their brand-new research study, Mooneys group asked whether those compressive forces could likewise safeguard from muscle atrophy. Nevertheless, when they directly compared muscle compression via the previous device to muscle extending and contraction by means of the MAGENTA gadget, just the latter had clear healing results in the mouse atrophy model.
” There is a great opportunity that distinct soft robotic techniques with their distinct impacts on muscle tissue might open up disease or injury-specific mechano-therapeutic avenues,” said Mooney.
To further expand the possibilities of MAGENTA, the group checked out whether the SMA spring might likewise be activated by laser light, which had not been revealed before and would make the approach basically cordless, expanding its therapeutic effectiveness. They demonstrated that an implanted MAGENTA device without any electric wires might operate as a light-responsive actuator and deform muscle tissue when irradiated with laser light through the overlying skin layer. While laser actuation did not attain the exact same frequencies as electrical actuation, and particularly fat tissue appeared to soak up some laser light, the researchers think that the demonstrated light level of sensitivity and efficiency of the gadget might be even more enhanced.
” The basic capabilities of MAGENTA and the fact that its assembly can be easily scaled from millimeters to several centimeters might make it fascinating as a central piece of future mechanotherapy not only to treat atrophy, but possibly also to accelerate regeneration in the skin, heart, and other locations that might gain from this form of mechanotransduction,” stated Nam.
” The growing awareness that mechanotherapy can resolve critical unmet needs in regenerative medication in manner ins which drug-based treatments simply can not, has actually stimulated a brand-new location of research study that links robotic developments with human physiology to the level of the molecular paths that are transducing different mechanical stimuli,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. “This study by Dave Mooney and his group is a really sophisticated and positive example of how this kind of mechanotherapy might be used medically in the future.” Ingber is likewise the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Childrens Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.
Referral: “Active tissue adhesive prevents and activates mechanosensors muscle atrophy” by Sungmin Nam, Bo Ri Seo, Alexander J. Najibi, Stephanie L. McNamara and David J. Mooney, 10 November 2022, Nature Materials.DOI: 10.1038/ s41563-022-01396-x.
The research study was funded by the National Institute of Dental and Craniofacial Research, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Science Foundations Materials Research Science and Engineering Center at Harvard University.
By Benjamin Boettner, Wyss Institute for Biologically Influenced Engineering at Harvard
December 30, 2022
Muscle atrophy is the wasting or loss of muscle mass and strength. It can occur as an outcome of disuse or it can be a symptom of specific neurological conditions. Atrophy can result in decreased mobility, impaired function, and decreased lifestyle.
An adhesive that can promote muscles to stretch and contract has been established– and it has the prospective to make it possible for and prevent healing from muscle atrophy.
Muscles can become weak and run out due to a lack of workout, such as when a limb is paralyzed in a cast, or gradually as individuals age. This condition, referred to as muscle atrophy, can also occur as an outcome of neurological disorders like ALS and MS, or as a reaction to particular illness consisting of cancer and diabetes.
Mechanotherapy, a kind of treatment that uses handbook or mechanical techniques, is thought to have the potential to help in tissue repair. Massage, which utilizes compressive stimulation to unwind muscles, is the most popular type of mechanotherapy, however, it is unclear whether extending and contracting muscles through external methods can also be effective as a treatment. There have actually been 2 significant challenges to studying this possibility: an absence of mechanical systems that can evenly use extending and contraction forces to muscles along their entire length, and the inefficient delivery of these mechanical stimuli to the surface area and much deeper layers of muscle tissue.
