Could the body’s clock help rehabilitation work better?

October 1, 2026

Emerging research suggests that the timing of rehabilitation may influence how musculoskeletal tissues respond to mechanical loading. At the AO Research Institute Davos (ARI), the RefineCF project is exploring whether the body's internal clocks could one day help guide more personalized approaches to cartilage repair and recovery.
 

Rehabilitation is usually prescribed in terms of exercises, repetitions, and recovery milestones. But researchers are increasingly asking whether another factor could influence outcomes: timing.

Scientists have long known that circadian rhythms regulate sleep, hormone production, metabolism, and other biological processes.  

However, more recent research has shown that these internal clocks are present not only in the brain but also in musculoskeletal tissues, including cartilage and intervertebral discs: Cartilage and disc cells maintain their own molecular clocks, helping regulate tissue maintenance, metabolism, and responses to mechanical stress.  

These findings have raised an important question: could the timing of rehabilitation exercises influence how tissues respond to treatment and repair themselves?

“It is becoming increasingly apparent that the response to a stimulus can be very different depending on the time of day it is applied,” said ARI Vice-Director Martin Stoddart, who is also the Regenerative Orthopaedics Program Leader. “It is exciting to think we may get improved outcomes just by doing the same thing at a different time.”
 

RefineCF: investigating timing

At the ARI, researchers are beginning to explore this possibility through RefineCF (RolE oF tIming iN mEchanically induced Cartilage Formation).

The project builds on previous work at the ARI showing that mechanical stimulation can guide mesenchymal stem cells toward cartilage formation. Using advanced multiaxial bioreactors, researchers can apply precisely controlled combinations of compression and shear forces that mimic the mechanical conditions experienced by articulating joints.

The RefineCF project investigates how biological timing interacts with mechanically induced cartilage formation. Researchers aim to better understand whether factors such as when loading begins, how long it is applied, and the timing of mechanical stimulation affect tissue responses.

“When looking at when to apply load, we are not just investigating which day to start loading, we are also looking into whether loading in the morning or the evening makes a difference. Similarly, should we be loading once a day or multiple times per day?” explained Stoddart.

By incorporating circadian timing into controlled bioreactor experiments, the ARI is exploring whether identical rehabilitation stimuli may produce different biological effects depending on when they are delivered.
 

Toward more personalized rehabilitation

Although the concept remains an emerging area of research, it represents a promising intersection of mechanobiology, tissue engineering, and chronobiology. The long-term goal is to generate evidence that could support more informed and personalized rehabilitation strategies following cartilage repair procedures.

“A greater understanding of circadian control of tissue healing has the potential to lead to evidence based, personalized rehabilitation protocols in future,” said Stoddart.

For now, no clinical recommendations can be made regarding optimal times of day for rehabilitation. However, projects such as the ARI’s RefineCF are investigating questions that have traditionally relied more on experience than experimental evidence.

As understanding of the body's internal clocks continues to grow, timing may eventually become another consideration alongside exercise type, intensity, and progression in orthopedic rehabilitation.

Why it matters
 

• Biological timing may influence tissue responses to rehabilitation. Cartilage and intervertebral disc cells contain molecular clocks that regulate maintenance, metabolism, and repair processes.
• Mechanical loading is both a therapeutic stimulus and a potential timing cue. Emerging evidence suggests loading can influence circadian activity within musculoskeletal tissues.
• Important rehabilitation questions remain unanswered. The optimal timing, duration, and scheduling of loading during rehabilitation are not yet supported by robust experimental evidence.
• If confirmed, circadian biology could become an additional variable in rehabilitation planning, helping support more evidence-based and personalized care.