When Luis Alvarez was about 11 years old, he accidentally lit a tree on fire while heating up pool chemicals. His interest in science persisted after that mishap, and he earned a master’s in chemical engineering from MIT in 1999. But it wasn’t until his service as a military intelligence officer in the US Army in Iraq that Alvarez realized he wanted to focus on developing treatments to spur tissue regeneration.
“Many of the people I was serving with were having severe injuries and coming back to the States, [and] having delayed amputations [and] other complications that were all related to the inability of modern medicine to correct tissue defects or to regenerate tissues,” he says. When he returned from Iraq, he went back to MIT with the aim of finding ways to better treat such patients.
Working with Linda Griffith of MIT’s biological engineering department and Richard Lee, a regenerative medicine researcher at Harvard University and Brigham and Women’s Hospital, Alvarez developed a technique to tether proteins to materials, and demonstrated it with a protein called epidermal growth factor. Cell culture experiments suggested that the surface-bound epidermal growth factor protected bone-building cells from inflammation in the damaged bone, allowing those cells to proliferate and drive healing in the area.
The overarching idea is that using this technology, you can modify any protein so that it sticks to an implant almost like a paint, and it will remain on the implant so you don’t have any risk of it bleeding away or diffusing away.—Luis Alvarez, Theradaptive
After earning his PhD in 2009, Alvarez continued his military service, this time as an army scientist managing research and development programs, and eventually as an instructor at West Point, where he’d attended undergrad. He also founded a company called Theradaptive to further develop and commercialize paint-like bioactive coatings for implants, similar to ones he’d worked on at MIT. He retired from the military in 2017. In addition to his work at Theradaptive, Alvarez is a co-founder of Elevian, a Harvard spinout developing therapies in stroke and age-associated neurological conditions.
Theradaptive’s team has developed a method to coat orthopedic implants with other molecules that might improve healing, such as a variation of bone morphogenetic protein 2 (BMP2), which is already used clinically to promote bone regeneration after spine surgery and other bone-related procedures. In work conducted with collaborators at Cleveland Clinic and presented at the 2020 Orthopedic Research Society Meeting, Alvarez and his colleagues found that goats treated for a 5-centimeter defect in a limb with a standard surgical procedure and an implant coated with Theradaptive’s BMP2 variant, called AMP2, exhibited complete healing in the bone, while those treated with the uncoated implant did not. The company hopes to begin clinical trials of AMP2 next year.
The overarching idea is “that using that technology, you can modify any protein so that it sticks to an implant almost like a paint,” Alvarez says. “And it will remain on the implant so you don’t have any risk of it bleeding away or diffusing away.”
Alvarez thinks the tethering approach will also be useful in other applications. He’s partnered with Colonel Leon Nesti, a former West Point classmate who is now a hand surgeon and researcher at Walter Reed National Military Medical Center, to evaluate AMP2 and to develop a separate therapy aimed at precision repair of hand bones. With many clinical drug delivery systems, “you essentially put a dose of a drug at one time point within the area of regeneration,” Nesti says, and “the initial concentration then very rapidly becomes metabolized or taken away from the site of injury.” Alvarez’s technology, in contrast, “allows the drug to stay at the site of regeneration for a much longer period of time, and be released in a much more controlled fashion,” he explains, “so its ultimate effectiveness is much greater.”
The fact that living tissues don’t currently integrate well with implanted materials is “one of the main hurdles in surgical treatment and replacement of tissue functions through foreign materials,” says Harald Ott, a surgeon and tissue engineering researcher at Massachusetts General Hospital. (Ott and Alvarez aren’t research collaborators, but Alvarez is on the scientific advisory board of a startup founded by Ott.) “I think improving that through changing the way cells interact with material is a very attractive proposition.”