Technique uses living cells to build engineered muscle tissue

The National Institutes of Health has awarded a three-year, $437,248 grant to a University of Arkansas biomedical engineering researcher to design and test a biomaterial that can regenerate damaged skeletal muscle.

Living cells secrete fibrous proteins and polysaccharide gels called extracellular matrix, which support cell survival and tissue strength. Minor muscle injuries affect tissue cells but not the extracellular components. In severe injuries, however, the extracellular matrix does not function properly and cannot initiate the healing process. Engineered “muscle-mimics” provide the molecules necessary to cue regeneration.

“When significant muscle volume is lost, the physical and chemical cues provided by the extracellular matrix are missing, and the volumetric muscle loss is instead replaced with scar tissue,” said Jeffrey Wolchok, assistant professor of biomedical engineering.

The grant will allow Wolchok and his research team to build muscle-mimicking biomaterials using a cellular approach and to test the material’s regenerative capacities.

“Like collecting honey from bees, we collect the extracellular matrix secreted by cells and put it together to build a biomaterial,” Wolchok said.

Wolchok grows cells inside a porous foam. These cells secrete extracellular matrix into the pores of the foam. The foam can then be sacrificed, or dissolved in a solvent, so only the extracellular matrix remains.

“We can use the sacrificial foam technique to build an engineered muscle-mimic scaffold capable of regenerating damaged skeletal muscle,” Wolchok said.

One example where this regeneration would help is rotator cuff injuries. Each year physicians operate on 400,000 rotator cuff injuries, and approximately one of three of those patients will repeat the surgery because the tendon holding the muscles together re-ruptures. Fatty tissue degeneration following the initial injury contributes to post-surgery tendon tears. Surgeons would use the muscle-mimicking biomaterial to repair the damaged skeletal muscle, including the rotator cuff muscles.

Wolchok said his engineered muscle-mimic may be injected into the injured tissue directly or combined with stem cells harvested from the patient. Potentially the stem cells and the extracellular matrix in the mimic would communicate with native cells and stimulate the regeneration of healthy muscle.

“Even a modest reduction to the failure rate could eliminate tens of thousands of repeat procedures and greatly reduce rotator cuff-related health care expenses,” Wolchok said.

Wolchok is the primary investigator in the Regenerative Biomaterials Laboratory at the University of Arkansas. He studies biomaterials derived from cells, tissue engineering and regenerative medicine and bioreactors. He also investigates the design of medical devices and the influence of mechanical force on cell behavior.