Massage not only makes muscles feel better, it makes them heal faster and stronger

Photo of a robot software interface device with a force sensor integrated with an electromagnetic actuator. Credits: BR Seo, et al. , Translational Medicine Science (2021)

Massage has been used to treat pain and injured muscles for over 3000 years. Today, many athletes swear to rehabilitate their bodies with massage guns. But other than making people feel good, do these “mechanotherapies” actually improve healing after serious injury? Wyss Institute for Biologically Inspired Engineering and John A at Harvard University. The answer is yes, according to a new study by researchers at the Paulson School of Engineering and Applied Sciences (SEAS).

Provides a constant and adjustable compressive force to the mouse using a custom designed robot system Muscles of the legs, The team found that this mechanical load (ML) was quickly cleared Immune cells called neutrophils by the tissues severely injured muscles. This process has also been suppressed Inflammatory cytokine It is released from the muscles by neutrophils and improves the process of regeneration of muscle fibers. The study is published on Scientific translation medicine..

“A lot of people are trying to study the beneficial effects of massage and other mechanical therapies on the body, but so far they have not been done in a systematic and reproducible way. Our job is, Mechanical stimulation and immune function. It can also be used in patients with diseases that promise regeneration of various tissues such as bones, tendons, hair, and skin and interfere with the use of drug interventions. said Bo Ri Seo. A postdoctoral fellow in the lab of Dr. Dave Mooney, Senior Faculty Member, at the Wyss Institute and SEAS.

More meticulous massage gun

Seo and his coauthors began studying the effects of mechanotherapy on injured tissue in mice a few years ago. Doubling the rate Muscle regeneration and loss Organization Scars for 2 weeks. Excited by the idea that mechanical stimulation alone can promote regeneration and strengthen muscle function, the team is exploring more deeply how the process works in the body and what parameters maximize healing. Decided to understand.

They are members of the Wyss Associate Faculty, Conor Walsh, Ph.D., in collaboration with the soft robotics experts at Harvard Biodesign Lab. Led to create a small device that uses sensors and actuators to monitor and control the force exerted on the limbs of a mouse. .. “The device we have created gives us precise control over parameters such as the amount and frequency of force applied, so that we can understand tissue healing with a much more systematic approach than the manual approach. “, did he declare. Two authors, Dr Christopher Payne, said. Harvard Biodesign Lab, former postdoctoral researcher at D., Wyss Institute, and now robotics engineer at Viam, Inc.

Demonstration of a robot actuator that applies a mechanical load to injured muscles of a mouse. Credits: BR Seo, et al. , Translational Medicine Science (2021)

When the device was ready, the team experimented with applying force to the muscles in the mouse’s legs using a soft silicone tip and used ultrasound to study what happened to the mouse. tissue accordingly. They observed that the muscles were under 10-40% tension and confirmed that the tissue was under mechanical forces. They also used this ultrasound image data to develop and validate computer models that could predict the amount of tissue tension under various loading forces.

The injured muscle was then subjected to constant and repetitive force for 14 days. Both treated and untreated muscles showed a decrease in the amount of damaged muscle fibers, but the decrease was more pronounced, the cross section of the fibers was larger in the treated muscles, and the treatment was greater. This shows that this resulted in the restoration and recovery of strength. It has been found that the greater the force applied during the treatment, the stronger the injured muscles and the more mechanotherapy improves muscle recovery after the injury. But how?

Drive out neutrophils to promote regeneration

To answer this question, the scientists conducted a detailed biological assessment to analyze various inflammation-related factors called cytokines and chemokines in both untreated and treated muscles. The cytokine subset was significantly reduced in the treated muscle after 3 days of mechanical therapy. These cytokines are associated with the movement of immune cells called neutrophils, which play many roles in the inflammatory process. Treated muscles also have fewer neutrophils in the tissue than untreated muscles, suggesting that a decrease in the cytokines that attract them resulted in a decrease in neutrophil infiltration.

The team had a hunch that the force exerted on muscles by mechanotherapy would effectively extract neutrophils and cytokines from damaged tissue. They confirmed this theory by injecting fluorescent molecules into the muscles and observing that the movement of the molecules became greater with the application of force, and supported the idea that this would help flush the muscle tissue. ..

To find out how neutrophils and their associated cytokines affect muscle fiber regeneration, scientists In vitro A study in which muscle progenitor cells (MPCs) were grown in medium in which neutrophils had already grown. They found that the number of MPCs was increasing, but the rate at which they differentiated (developed elsewhere). Cell type) Decrease, suggesting that neutrophil secreting factors stimulate muscle cell growth, but the long-term presence of these factors impairs the production of new muscle fibers.

A robotic device combined with ultrasound imaging of stimulated deformities of muscle tissue in the limbs. Credits: BR Seo, et al. , Translational Medicine Science (2021)

“Neutrophils are known to kill and eliminate pathogens and damaged tissue, but this study identified a direct effect on the behavior of muscle progenitor cells,” said a former graduate student of the Wyss Institute. Co-second author Stephanie McNamara said. Currently MD-Ph.D. Student at Harvard Medical School (HMS). “The inflammatory response is important for regeneration in the early stages of healing, but it is equally important that the inflammation is resolved quickly so that the regeneration process can be fully carried out.”

Then Seo and his colleague came back to them In vivo Models and types of analysis Muscle fiber In treated and untreated mice 14 days after injury. They found that type IIX fibers were prevalent in healthy and treated muscles, but untreated injured muscles had a lower number of type IIX fibers and an increased number of type IIA fibers. Was here. This difference explained the increase in fiber size and the production of greater strength in the treated muscles, as IIX fibers generate more strength than IIA fibers.

Finally, the team depleted mouse neutrophils three days after injury to ensure optimal time for neutrophils to be present in the injured muscle. Muscles from treated mice exhibit larger fiber size and greater strength recovery than untreated mice, requiring neutrophils in the early stages of injury recovery, but clearing neutrophils early from the injury site . It was confirmed that muscle regeneration was improved.

“These results are remarkable because they show that they can affect the functioning of the body’s immune system in a non-invasive way without the use of drugs,” says Paul A. of SEAS. Walsh, who is also a professor of applied science in meeder engineering, said. The group has experience in developing wearable technologies for the diagnosis and treatment of disease. “This is a great incentive for the development of external mechanical interventions that help accelerate and improve healing of muscles and tissues that can be quickly transformed in the clinic. “

The team continues to study this series of studies on several laboratory projects. They plan to test this mechanotherapy approach on larger animals in order to be able to test its effectiveness in humans. They also want to test different types of injuries, age-related muscle loss, and improved muscle performance.

“Although the fields of mechanotherapy and immunotherapy rarely interact, this study takes into account both physical and biological factors when studying and working to improve human health. It just goes to show how important this is, ”says Robert P. Pincus Family, professor of bioengineering in treaty and SEAS.

“The idea that mechanics affect the functioning of cells and tissues has been ridiculed for decades. Scientists have made great strides in establishing acceptance of this fact, but the process Little is yet known about how it actually works at the organ level. This study reveals a previously unknown type of interaction between mechanobiology and immunology. logic Tissue healing can be as powerful as chemotherapy or gene therapy, but in addition to explaining a new form of mechanotherapy that is much simpler and less invasive. ” Judah Folkman Professor of Vascular Biology Professor of the Vascular Biology program at (HMS) and Boston Children’s Hospital, and of bioengineering at SEAS.


Train your muscles with anti-inflammatory nanoparticle therapy


For more information:
Regeneration of skeletal muscle with clearance of neutrophils by robotic action, Scientific translation medicine (2021). www.science.org/doi/10.1126/scitranslmed.abe8868

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