To Mend Difficult Breaks, Try Porous Implants Treated with “Bone Paint”

A bone regeneration technology from Theradaptive can fill large gaps, potentially saving limbs and accomplishing other feats of preservation, restoration, or reconstruction

Theradaptive is racing to develop its targeted bone-growing technology. The sooner the technology is in commercial use, the sooner it will help patients who have broken bones that just won’t heal. The patients who could benefit include those who have already suffered injury. (In patients with nonhealing breaks, amputations can be required months or even years after the initial injury.)

Theradaptive’s technology can turn any protein into a variant that binds to implant materials, allowing the formation of a paint-like coating that stays in place, helping to prevent off-target effects. In the case of tissue regeneration, it allows physicians to regrow tissue with great precision.

Learning to stay on target

Bone morphogenetic protein-2 (BMP-2) is a vital component of the body’s bone-healing response, a process that also involves the recruitment of stem cells to the site of injury. To harness BMP-2 in therapeutic applications, Theradaptive engineers led by Luis Alvarez, PhD, the company’s founder, have developed a platform technology to modify BMP-2 so that it binds well to implant materials and surgical devices.

David Stewart Inspects Package
Theradaptive’s technology can turn any protein into a variant that binds to implant materials, allowing the formation of a paint-like coating that stays in place, helping to prevent off-target effects. In the case of tissue regeneration, it allows physicians to regrow tissue with great precision.

The lead variant of BMP-2 developed by Theradaptive is called AMP-2. AMP-2 is applied to guide migrating stem cells into implants and ensure that bone is formed only where it is needed. Using this approach, Theradaptive asserts, is safer and more precise than using existing technologies. The company adds that when AMP-2 is applied, major fractures can be healed much sooner and with few off-target effects. Although the company focuses on AMP-2, Alvarez says, “We can turn almost any protein into a material-adhesive protein.”

AMP-2 has been called “bone paint,” and the name is fairly accurate. “With Theradaptive’s technology, you can coat an implant and insert precisely at the defect,” asserts Alvarez, who emphasizes that the bone regenerative protein then stays in place. In contrast, in routine bone grafts today, the protein easily diffuses away from the site of the graft. “You can place the protein in a bone defect or in the spine,” Alvarez says of the conventional technology, “but there’s no easy way to keep it there.”

The base implant itself is composed of calcium phosphate, which eventually is reabsorbed by the body. By the time that happens, new bone has formed at the site of the fracture, leaving the bone there as strong as or stronger than it was before the injury.

As part of a platform technology, AMP-2 has the potential to serve a large market. There are applications to heal multiple types of trauma to bone, including fractures among the elderly, and there are applications in spinal fusion to treat intractable back pain.

Answering a call to healing

The need for better bone regeneration technology struck Alvarez when he was still a lieutenant colonel in the U.S. Army. “When I was in Iraq, service members I’d served with suffered amputations months after returning home with injuries,” he recalls. “Modern medicine could initially save their limbs, but if the bone didn’t heal, the limbs would need to be amputated, often months after the initial injury.”

He returned home from the combat zone in 2005 determined to change that reality. He convinced the Army to let him complete a PhD program in biological engineering at the Massachusetts Institute of Technology. He began developing what would become Theradaptive’s foundational technology. Eventually, in 2017, Alvarez retired from the military and formed Theradaptive. “The company was very small,” he says. Initially, Theradaptive licensed its technology from the U.S. Army.

“The technology hadn’t yet been tested in animals,” Alvarez elaborates. “We were just working out the details. We established a team to develop the technology and start fundraising.”

Today, the company has raised more than $17.4 million, including a recent $3 million contract with the Department of Defense and a $6.2 million Series A investment round led by AMP Squared Capital Partners and joined by the Maryland Venture Fund and ORTHOReBIRTH. “We already have commitments for the Series B round,” he points out, “which we expect to close later in 2021.”

Theradaptive computational platform diagram
Theradaptive uses a computational platform to determine how recombinant proteins may be converted into material-binding variants. Once these variants are generated, they may be applied in a one-step process to target materials such as inactive implants. The result: bioactive material carriers that release therapeutic proteins locally and avoid causing off-target effects.

Realizing orthopedic applications

“The AMP-2 implant is advancing into clinical development,” Alvarez states. “Human trials are planned for 2022.”

Optimism about the upcoming trials is justified, Alvarez suggests, because the implant employs a therapeutic approach that is inherently safe. “The protein can’t spread into other tissues,” he insists. The Food and Drug Administration, he adds, “recognizes the safety aspects of this kind of therapeutic.”

So does one of Theradaptive’s investors, namely, ORTHOReBIRTH, a Japanese regenerative medicine company. In late 2019, Theradaptive entered into an agreement with them to combine Theradaptive’s BMP-2 with ORTHOReBIRTH’s cotton-like void-filling material ReBOSSIS to treat congenital skeletal defects and traumatic bone injuries.

In that collaboration, AMP-2 protein binds with high affinity to ReBOSSIS to enable robust and precise bone regeneration. The combined technology, dubbed OsteoAdapt, has been used successfully in animals. For example, George Muschler, MD, vice chair of the Orthopaedic and Rheumatologic Institute within the Cleveland Clinic and a Theradaptive advisor, used the technology to heal 5-cm defects in the leg bones of goats.

“That’s hard to do,” Alvarez points out. “AMP-2 has beaten the standard of care in every preclinical study so far.” The project, he adds, “is going well.”

Exploring new possibilities

Although Theradaptive is currently focused on orthopedics, the platform technology seems to have multiple additional applications. For example, possible indications for these biologically active tissue-growth-stimulating implants include dermal and vascular repairs. Alvarez maintains, “We have proof of concept.”

The company is considering how it could form partnerships to expand material options and potential applications. “We’ve received a lot of interest,” Alvarez reports, “and we’re in discussions with several potential strategic partners for a variety of indications.”

Bone regeneration is a challenge globally, for both developed and emerging economies. Between trauma and spine applications, it represented a market that had an estimated value of nearly $10.3 billion in 2020 and is expected to grow more than 3% per year through 2027. Growth is driven by the increase in traumatic injuries as well as by the continuing maturation of regenerative medicine therapeutics.

With the opportunity to pursue so many applications—and to bring much needed relief to so many—there is a natural tendency for Theradaptive to explore all of its options simultaneously. “We see the potential,” Alvarez says, “and have to remind ourselves to focus on the initial clinical indication.”

For now, that means Theradaptive remains focused on orthopedics. “Our challenge is a battle against the clock to get this therapy to patients,” Alvarez stresses. “There’s no time for complacency.”