Elderly people receiving robotic stimulation to repair damaged muscle may need to take anti-inflammatory drugs to benefit from the treatment, a study in mice suggests.
Researchers found that muscle stem cells and immune cells responded differently to these “mechanotherapies” depending on age.
Older animals did not gain the benefits from the robot-actuated loading seen in younger animals as it induced inflammation, which interfered with muscle regeneration.
However, anti-inflammatory treatment using glucocorticoids mitigated the negative effects on stem cells and enabled the aged muscle to respond positively to the robot-based mechanical loading (ML).
The researchers say their findings, in Science Robotics, highlight the importance of biological considerations, such as age, in the translation of robot-based technologies.
“Geriatric trauma is a field of medicine that stands to benefit substantially from robot-assisted tissue regeneration technologies,” they predict.
“This work demonstrates the importance of using pharmaceutical control of age-associated biological changes as an adjunct to robot-based therapy to harness the value of regenerative robotics observed in young tissue for the aged.”
Regenerative robotics is an emerging field aimed to promote tissue healing by leveraging the biophysical sensing capabilities of the body.
Noninvasive, robot-based ML therapies, also known as mechanotherapies, have been explored for skeletal muscle repair given its well-known sensitivity to mechanical cues.
Muscle stem cells exhibit activation and proliferation in response to ML and, after injury, mechanotherapy has been found to offer therapeutic benefits by enhancing muscle function, improving structural repair of damaged myofibers, and reducing tissue fibrosis in vivo.
David Mooney, PhD, a professor of bioengineering at Harvard University, and team examined the age-dependent effects of daily treatment with a noninvasive, load-controlled robotic device on muscle repair in mice with severe hindlimb injury.
A robotic loading device with a soft elastomeric interface was used to apply cyclic compressive loading to the tibialis anterior muscle of the injured hindlimb, with feedback control ensuring consistent, repeatable loading across treatment sessions.
Based on previous reports, the team hypothesized that ML would promote muscle repair in older animals by downregulating the chronic aged inflammatory response while simultaneously stimulating the stem cell population.
Instead, they observed that the same type of ML that conferred benefits on young muscle after injury was ineffective in facilitating recovery for injured aged muscle.
Moreover, there was a notable exacerbation of inflammation in injured aged muscles in response to ML, as well as a disruption in the regenerative behavior of aged muscle stem cells.
ML in younger animals resulted in improvements in muscular contraction after two weeks of treatment compared with control animals.
But these benefits were not seen in older animals, with no significant improvements in muscle function for older animals after three weeks of treatment.
Histological analysis revealed that ML significantly reduced the percentage of damaged myofibers and the degree of tissue fibrosis in injured young muscle.
However, injured aged muscles still exhibited significant muscle damage and calcification, with no such improvement.
The researchers then introduced anti-inflammatory therapy alongside ML treatment via systemic administration of the glucocorticoid triamcinolone acetonide and found that it reduced inflammation, increased perfusion, reduced necrosis, and improved myogenic differentiation in aged muscle.
After a week of treatment there was a significant improvement in the contractile force of injured aged muscles in both animals treated with anti-inflammatories only or in combination with ML compared with both untreated controls and muscles treated with ML only.
By day 14, the combination of ML and glucocorticoids resulted in greater muscle contraction benefits than the other groups, including those receiving only the anti-inflammatories.
The researchers report: “Age-dependent differences in the response of injured skeletal muscle to robot-actuated ML were found here, and a potential immunotherapeutic avenue to regenerate aged skeletal muscle with non-invasive mechanotherapy was identified.”
