The combination of mechanotherapy — the use of mechanical forces to stimulate tissue healing — and anti-inflammatory treatment can help heal damage in aged muscles, according to a new study.
Researchers at the Wyss Institute for Biologically Inspired Engineering and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) found that in young animals, mechanotherapy accelerated muscle healing by mitigating inflammation. When used on aged muscle, however, the same treatment actually had the opposite effect — mechanotherapy amplified inflammation in aged muscle, hindering the normal healing process by disrupting the behavior of muscle stem cells.
The researchers then found that combining mechanotherapy with anti-inflammatory treatment significantly improved healing in aged muscles and was superior to anti-inflammatory treatment alone.
In mice, the researchers found that administering anti-inflammatory therapy in the form of the steroid hormones glucocorticoids alongside mechanotherapy suppressed key pro-inflammatory pathways and reduced overall inflammation levels in injured aged muscle to those seen in injured young muscle. By removing the negative impacts of inflammation, injured aged muscles could positively respond to robot-delivered mechanical loading.
“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 Wyss core faculty member David Mooney, 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.”
Added first author Stephanie McNamara, a graduate student on Mooney’s team: “It’s important to question whether the same mechanisms seen in studies performed in young animals stay the same 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.”
The study was published in Science Robotics.
