Tricking the Body into Replacing Lost Muscle

The human body can heal itself, but only up to a point. If an injury removes 20% or more of a muscle - as can happen in car accidents, certain surgeries or explosions in combat zones - natural processes can't, on their own, replace it. Instead, the wound seals up, covered by scar tissue.

"The body sees this extensive loss of tissue as an insurmountable void," says Jonathan Grasman, an assistant professor of biomedical engineering.

His lab is developing implants to boost muscles' regenerative power and provide a more effective option than the surgeries currently used to treat these injuries. The material he and his colleagues are developing mimics the internal scaffolding that organizes muscle, serving as a template for healing.

"I like to describe it as tricking the body into thinking that it has a smaller injury," Grasman says.

After more minor damage, including that caused by a strenuous workout, muscle fiber-forming cells known as myoblasts arrive to heal damaged muscle fibers and produce new ones. But this repair mechanism falls short in more traumatic injuries, such as those involving volumetric muscle loss.

To treat these bigger wounds, doctors remove muscle from elsewhere in the body, typically from within large muscles such as the quadriceps of the thigh, or the back's broad latissimus dorsi. They then graft this muscle into the wound. This surgery has some significant drawbacks: Grafting creates a second injury with all the accompanying risks, is prone to complications, and, even when successful, leaves patients with reduced control over fine movement. Scar tissue, for example, is composed of aligned collagen fibers that don't contract like myofibers, thus limiting functionality within muscle.

Grasman and others are exploring alternative ways to augment healing. One strategy would fill the wound with muscle grown in a lab, possibly from patients' own cells. Another approach - and the focus of his recent work - provides a structure to guide cells already present at the wound site as they form new muscle.

Within muscle, cable-like muscle fibers run parallel to each other, generating force by contracting. A framework made of collagen, a protein that provides structure throughout the body, organizes these fibers, which must align for muscles to work as they should. Following nature's lead, Grasman and his colleagues are experimenting with sponges made of collagen, containing pores that mimic this architecture.

In recent experiments described in the Journal of Functional Biomaterials, his team focused on determining the best size for the pores. Because they create these openings by freezing the collagen, researchers can manipulate their size by adjusting the temperature. These dimensions matter because if the pores are too small, the myoblasts can't enter to form fibers. If the pores are too large, they can't guide fiber growth. In this study, they determined they could best balance these competing needs by making the sponges at -20 degrees Celsius.

Recovering from an injury requires more than just making new muscle fibers, however. New blood vessels must infiltrate the muscle to feed it oxygen, and new nerves must carry information to and from the brain. With help from a collaborator, Grasman's lab is experimenting with making collagen sponges containing molecules that promote the growth of new blood vessels. His group is also exploring a variety of ways to encourage the growth of neurons and examining the potentially beneficial interactions between these cells and those that line blood vessels.

In the end, Grasman hopes to create a material that requires minimal preparation.

"Hypothetically, it could be two components that you mix together, wait two hours, then give to the surgeon," he says. "Implanting it would then allow native muscle to regrow and restore the patient's ability to function normally."

Although other groups are working on this problem, no alternatives - involving cells or scaffolding - have received approval from the FDA for use in injuries.

While the need is very real, Grasman traces his inspiration back to a long-standing interest in science fiction and fantasy stories in which bodies are created from mere DNA or wounds healed with a spell. Regeneration also occurs in nature, he notes. Starfish and salamanders can regenerate limbs; cut in half, each side of a worm can turn into another worm.

The prospect of accomplishing something similar for humans remains far off on the horizon, however. "My dream is to team up with somebody who understands bone and derive a strategy for potentially recapitulating an entire limb," Grasman says.

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