In the quest to find innovative ways to treat muscle injuries in the aging population, a multidisciplinary study led by researchers at the Wyss Institute for Biologically Inspired Engineering and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) has recently discovered that tailored mechanotherapy can significantly improve healing in elderly patients. This breakthrough could pave the way for new, noninvasive therapeutic options for individuals of all ages.
Mechanotherapy has been used for decades in physical therapy, employing mechanical forces—including massage—to stimulate tissue healing. However, the biological basis and optimal settings for noninvasive mechanotherapies have remained poorly understood, particularly for elderly patients.
The research team, led by Wyss core faculty member David Mooney in collaboration with associate faculty member and Paul A. Maeder Professor of Engineering and Applied Sciences Conor Walsh, investigated whether elderly patients could benefit from tailored mechanotherapy for severely injured muscles in the same way that young patients can.
To test this hypothesis, the researchers developed a robotic mechanotherapy device that functions like a highly advanced massage gun. This technology enabled the precise delivery of mechanotherapy to injured muscles in mice, allowing the team to measure its biological effects.
The study revealed that, in young animals, mechanotherapy accelerated muscle healing by mitigating inflammation. However, in aged muscle, the same treatment had
the opposite effect. The settings that promoted healing in young muscle actually exacerbated injury in old muscle by amplifying inflammation and disrupting the behavior of muscle stem cells, which are responsible for replacing damaged muscle tissue.
In search of a solution, the researchers asked if controlling inflammation alongside delivering mechanotherapy could help heal aged muscles. Their findings confirmed that combining mechanotherapy with anti-inflammatory treatment significantly improved healing in aged muscles and was superior to anti-inflammatory treatment alone. This groundbreaking work, published in Science Robotics, presents an exciting, noninvasive therapeutic avenue for elderly patients.
“Our study highlights critical differences in how muscle stem cells and immune cells respond to mechanical forces in the context of age, and how upregulated inflammation additionally compromises the function of aged stem cells needed for the regeneration of old muscles,” said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS. “Muscle mechanotherapies likely thus won’t be a ‘one-size-fits-all.’ To realize their benefits, they will have to be tailored to patient populations, and specifically for aged individuals, it will be key to modulate inflammation.”
The team found that administering anti-inflammatory therapy in the form of glucocorticoid steroid hormones alongside mechanotherapy suppressed key pro-inflammatory pathways and reduced overall inflammation levels in injured aged muscle to those seen in injured young muscle. At a cellular level, muscle cells continued to experience mechanotransduction, and by removing the negative impacts
of inflammation, injured aged muscles could positively respond to the robot-delivered mechanical loading.
First author Stephanie McNamara, a graduate student on Mooney’s team who is currently enrolled in the joint Harvard/MIT M.D.-Ph.D. program, explained the significance of their findings: “We showed that although aged stem cell behavior was disrupted by the elevated inflammation, they were still able to ‘feel’ the mechanical forces of loading as we demonstrated by the activation of these pathways. This actually was what prompted us to ask whether controlling inflammation might enable these cells to respond to the mechanical stimuli — and indeed it did.”
McNamara emphasized the importance of considering the changes in muscle healing and inflammation processes as the body ages. “By leveraging what we learned in this study and our previous work and combining it with growing expertise in wearable soft robotic systems, we believe that in the future personalized mechanotherapeutic approaches can be developed to heal injuries across all ages.”
Other authors involved in the study include members of Mooney and Walsh’s research groups, such as Bo Ri Seo, Benjamin Freedman, Emily Roloson, Jonathan Alvarez, C.T. O’Neill, and Herman Vandenburgh, professor emeritus at Brown University, Providence, Rhode Island.
This groundbreaking research offers new hope for the aging population and opens the door to further exploration of personalized mechanotherapeutic approaches. By tailoring treatments to individual patients
