Rebuilding muscle, skin, and fat with injectable gel

Car crashes, battle wounds, and surgeries can leave people with gaping holes in soft tissue that are often too large for their bodies to repair. Now, researchers have developed a nanofiber-reinforced injectable gel that can rebuild missing muscle and connective tissues by serving as a scaffold and recruiting the body’s wound-healing cells. So far, the team has tested the material only in rats and rabbits. But if it performs as well in humans, it could give reconstructive surgeons a fast and easy way to help patients regenerate lost tissues without scarring or deformity.

“Soft tissue losses are a ubiquitous problem in clinical medicine,” says Sashank Reddy, a reconstructive surgeon at the Johns Hopkins University School of Medicine in Baltimore, Maryland. Surgeons can transplant tissue from another body region to the injury site. But that involves trauma for patients and tissue loss from another part of the body. Surgeons can also insert synthetic implants. But immune cells typically just wall off those implants, leaving behind thick, fibrous scars.

Then there are gellike fillers. When injuries are small—on the order of fingertip-size—surgeons often inject a gel made from hyaluronic acid (HA) that immune cells called macrophages can infiltrate. As they burrow inside and encounter HA molecules, macrophages typically send out signals that recruit blood vessel–forming cells and other cells that help repair the damage. But with larger gaps in tissue, HA gels are typically too squishy to hold their shape. Researchers have tried to fortify gels by linking gel molecules. But to make gels strong and tough enough to behave like tissue, researchers must add so many links that they create a stiff 3D mesh. But its pores are too small for macrophages and other cells to penetrate. “It changes the biology,” says Jennifer Elisseeff, a biomedical engineer at Johns Hopkins who was not part of Reddy’s team. As a result, the macrophages release signals that lead to scar tissue.

Now, Reddy and his colleagues have come up with a better way to reinforce HA gels. They first created nanofibers out of a biodegradable polymer used for decades in dissolvable sutures, called polycaprolactone. They then treated the fibers so that some would contain molecular linkers designed to bind to HA. An hourslong process formed bonds between the molecular linkers and the HA molecules, creating a gel that was as resilient as soft tissue. And, much as a bit of rebar reinforces concrete, the gel needed only a small volume of nanofibers to become rigid. That small amount meant the gel still had gaps large enough for cells to easily pass through. The resulting 3D mesh, says Reddy, has a striking resemblance to the body’s extracellular matrix, the natural scaffolding for healthy tissues.

To test their material, Reddy and his colleagues injected it into rabbits in which some fat had been surgically excised, before the material stiffened. Not only did the gel take the shape of the missing tissue as it firmed up, but after it did, macrophages readily infiltrated it and released signals that recruited blood vessel–forming cells, among others. The animals were able to rebuild chunks of tissue as large as 10 cubic centimeters, about the size of a human finger, researchers report today in Science Translational Medicine.

The new gel is “cutting edge, scientifically,” says Ali Khademhosseini, a bioengineer at the University of California, Los Angeles, who wasn’t involved in the research. He notes that, unlike other gels, this one does not include growth factors and other biological signaling molecules, instead relying on the body to supply its own. That simplicity could make it easier for the gel to pass muster with the U.S. Food and Drug Administration, Khademhosseini says.

The gel could also help repair soft tissues with specific functions, like heart muscle cells. Hai-Quan Mao, a biomaterials expert and member of the team from Johns Hopkins, says the researchers hope to seed the matrix with stem cells that form cardiac tissue, in order to help repair tissue damage after a heart attack. That’s still in the research phase; in the meantime, the researchers have already formed a company to commercialize the technology, called LifeSprout.