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Torn rotator cuff or ligament? Northeastern team could speed your recovery

Northeastern bioengineering professor Jeff Ruberti and former Northeastern University graduate and Ph.D. Jeff Paten study the healing process on the tissue of a rat bone in the Interdisciplinary Science and Engineering Complex. Photo by Alyssa Stone/Northeastern University

A Northeastern University professor has teamed up with one of his former graduate students to develop a new soft tissue repair process they believe could revolutionize rehabilitative medicine.

Instead of waiting until injuries such as damage to the rotator cuff get bad enough to require surgery, the idea is to inject liquid crystal collagen into wounds and tears to accelerate healing and repair the injured tissues, says bioengineering professor Jeffrey W. Ruberti.

“It’s a concept I’ve been working on for 15 to 20 years,” says Ruberti, who in November started a spinoff from his lab called BrilliantStrings Therapeutics with Northeastern University graduate and Ph.D. Jeff Paten to develop the product.

Future candidates for the injectable treatment include orthopedic patients who “are in pain on a daily basis but are told to wait and see if their injury progresses (enough) to warrant surgery or is lucky enough to naturally heal,” says Paten, chief scientific officer of BrilliantStrings Therapeutics.

The scientists are currently testing the concept to see if the active collagen integrates into the repairing tissues of rats with rotator cuff injuries.

The next step is to obtain seed money for further animal testing and then funding for clinical trials, Ruberti says.

“Given a few years to get this nailed down, we’re going to be turning months of healing into weeks of healing and then days of healing,” Paten says.

A repaired rat rotator cuff tendon is positioned for a laster geometric scan. Photo by Alyssa Stone/Northeastern University

The spinoff is called BrilliantStrings after the strands of collagen that make up the connective load bearing platform for body parts ranging from cartilage and bones to tendons and corneas, Ruberti says.

A collagen molecule is long and skinny—150 times longer than it is wide, Ruberti says.

“It’s like a little string. It pretty much connects everything together. It’s the most abundant protein in your body.”

Ruberti says that over the years he’s discovered a unique way to harness the special healing properties of collagen.

The standard concept is that cells must work hard to build structures and repair injuries, akin to construction workers nailing every board in place, he says.

But what if cells had help—a lot of help?

“I had this thought that this material (collagen) may actually seek its low energy state, and that low energy state might be healthy tissue,” Ruberti says.

He says the lowest energy state happens to be in the path of force when tension is applied, such as when a muscle contracts and pulls against the bone, he says.

Ruberti says to imagine a string pulled tight. The tension and energy from the pulling makes it easier to cut.

“What I noticed years ago about collagen is that when it’s stretched, it’s harder for enzymes that clear out surplus material to cut it,” he says.

“Pulling on it makes it more comfortable,” Ruberti says. “It’s in its happy place under a load.”

Ruberti says his lab has been able to demonstrate this process by putting collagen in droplet form and using a glass micro needle to pull out a fiber.

The tension of pulling produces a tiny fibril like a tendon, Ruberti says. “It forms a structure just because you pulled it.”

Force drives structure formation, much like a weight lifter using heavier weights builds more muscle, Ruberti says. 

In tissue repairs, the concept is that the collagen will try to bridge the gap between tears, Ruberti says.

“The collagen is always trying to fix holes,” he says. Bridging the gap between tears puts it in a state of tension—its happy place—and prevents it from being cleared by enzymes so that it can make repairs, he says.

“It’s a pretty novel approach,” Paten says.

Most researchers are taking the tack of stimulating cells, such as with platelet rich plasma treatment, he says. 

“We’re taking a different approach.”

BrilliantStrings Therapeutics is currently testing the methodology in a rodent model, comparing the effectiveness of collagen injections in healing rotator cuff injuries to natural healing from saline solutions in the animal, Paten says.

“We’re initially checking to see if there is any sort of immune reaction” and whether the location of the injury has returned to normal healthy tissue, he says.

Human trials won’t take place for a while, Ruberti says.

He says his lab invented the liquid crystal formulation needed to deliver collagen as a therapeutic.

“There’s 10 patents behind us, 25 research papers on the concept and about $6 million from the NIH,” Ruberti says. 

And Northeastern University bioengineering capstone students recently developed a CRISPR method to accelerate production of human collagen cells, Ruberti says.

Paten, who received his undergraduate degree, doctorate and post-doc from Northeastern University, says he recently got a patent for developing a method to keep collagen soluble at 100 times the previously possible concentration for delivery through a syringe. Paten is excited to explore how this method could synergize with Ruberti’s liquid crystalline collagen. He expects they can produce a high efficacy dose of biologics to drastically accelerate the repair process.

The majority of orthopedic patients suffer from small to mid-level tears that are not suitable for surgery, says Paten, who is also a lecturer at the John A. Paulson School of Engineering at Harvard University.

What these patients could use is an ultrasound-guided injection, Paten says. “With this technology, we can put the right molecules in the right place to directly make the repair.”

There is a potentially huge market for a product that holds the promise of injectable collagen, which can also be delivered in a patch for those already requiring open surgery, Ruberti says.

Every year 4.5 million people seek medical help for shoulder pain due to rotator cuff injuries, and only 300,000 of them qualify for surgical repairs, he says.

The injectable formulation could help the other 4.2 million individuals, Ruberti says.

Patients who do have operations can also benefit from a collagen patch whose molecules migrate into the repair site, he says.

 “The patch basically disappears into a tendon. It becomes the new tendon. Our material is designed to become a permanent part of your body,” Ruberti says.

He says the potential market for the BrilliantStrings Therapeutics product is $100 billion.

“The market out there is not just for ligaments and tendons,” Ruberti says. 

He says if successful in practice it could help heal skin injuries, diabetic ulcers and burns as well as being an active ingredient in cosmetics.

“There are a lot of places where I believe we can help.”

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