Everyone knows how important exercise is to maintaining healthy muscles.

As it turns out, exercise is crucial even to lab-grown muscles. According to new research from the Wake Forest Institute for Regenerative Medicine (WFIRM), exercise is key to building a new kind of muscle-like implant. These implants can potentially repair muscle damage from injury or disease.

The process involved taking cells derived from muscle tissue and placing them onto biocompatible material. That material is then “exercised” in the lab, which allows the implant to prompt muscle regeneration and a significant recovery of function.

The achievement gives hope to the ability to one day treat human patients that suffer from muscle defects, such as cleft lip, or those that have sustained traumatic injury.

“The potential benefits of tissue engineering are huge,” said George Christ, Ph.D., a professor at the WFIRM. “In fact, our relatively limited capacity for regeneration, shortages of donor tissues/organs and increasing lifespan have combined to create a huge demand for regenerative medicine technologies.”

‘Exercising’ Implants Key to Success

Christ’s research is a significant breakthrough in the advancement of lab-engineered muscle implants.

“Prior to these studies there was no research documenting that ‘exercising’ engineered muscle implants in the lab would positively impact the quality of the regenerative response observed in the body.” said Christ. “This represents a paradigm shift in the way we think about tissue engineering for muscle repair.”

In July, Christ’s team reported the results from their second round of experiments. The research involved taking small samples of muscle tissue from rats and mice and processing them in order to extract cells, which were then multiplied in the lab. These cells were then placed onto strips of natural biological material derived from pig bladder, but with all cells removed, which is known to be compatible with the body.

Researchers placed these strips in computer-controlled devices that slowly expanded and contracted, or “exercised” them. Christ’s team next implanted the strips into mice with back muscle removed to create functional impairment. While these strips were “muscle-like” when researchers implanted them, they were not functional.

To measure results, Christ’s team compared four groups of mice. The control group, against which other groups would be measured, received no surgical repair. One group received implants that were not exercised beforehand, another received implants that had been exercised for five to seven days and the final group had extra cells added halfway through the exercise process.

Research Shows Implants Restore Muscle Function

Results showed that exercising the implants yielded significant differences in both muscle development and function. Two months after the implants, the mice that received implants with extra cells added showed a threefold increase in muscle force. The muscle’s ability to produce force is what gives it the ability to perform everyday tasks.

“The implant that wasn’t exercised, or pre-conditioned, was able to accelerate the repair process, but recovery then stopped,” said Christ. “On the other hand, when you exercise the implant, there is a more prolonged and extensive functional recovery. Through exercising the implant, you can increase both the rate and the magnitude of the recovery.”

Christ’s team also found that new muscle tissue developed both in the implant and the native tissue surrounding the implant. The discovery suggests that the implant accelerates the body’s natural healing response, prompting it to repair existing muscle tissue as well as grow new tissue.

The results also suggest that the same type of success could be replicated in humans.

“If these same results were repeated in humans, the recovery in function would clearly be considered significant,” said Christ. “Within two months after implantation, the force generated by the repaired muscle is 70 percent that of native tissue, compared to 30 percent in

Technology Could Treat Cleft Lip, Battle Wounds

The technology could have a tremendous impact on treating birth defects.

“The first proposed clinical indication for the muscle repair technology is treatment of secondary cleft lip deformities in healthy patients who have been incompletely corrected with current methods,” said Christ.

Cleft lip and palate is a relatively common birth defect where a gap in muscle tissue prevents typical facial development. The Centers for Disease Control and Prevention (CDC) estimates that one in 700 babies are born each year with a cleft lip or palate. Children with the defect often undergo multiple surgeries to correct the condition, with doctors either transplanting muscle tissue from other parts of their body to the face or stretching existing muscle to cover the gap.

The implants being researched by Christ’s team are the same size required for these types of surgeries, making the application of this technology to these defects a natural fit.

Along with treating cleft lip and palate, one of the biggest impacts this research could have is in treating injuries, such as those sustained by soldiers in battle.

The technology employed by Christ and his team was originally developed under the Armed Forces Institute of Regenerative Medicine with funding from the Department of Defense and the National Institutes of Health. The technology was developed with the long-term goal of treating severe head and facial injuries sustained by military personnel.

“If successful, there are numerous other potential indications, such as Bell’s Palsy, and a host other volumetric muscle loss injuries, such as those produced by accidents in the civilian population and the battlefield trauma injuries suffered by our wounded warriors in Iraq and Afghanistan,” he said.

Christ and his team are working to continue their research with human trials. “We are in currently in discussions with the FDA about this technology and hope to be able to try it in patients in the next few years, but as we are all aware, the regulatory path can be slow and unpredictable,” he said.

(C) NC Biotech Center