The natural processes of wound or bone healing rely on the growth of new blood vessels, or angiogenesis. If someone breaks a bone, it is standard practice to apply a cast and immobilize the broken bone, so that healing can proceed without mechanical distortion. Additionally, there currently are options like dry needling therapy that can assist in keeping the healing process pain free.

After those initial stages of healing, applying surprising amounts of pressure can encourage angiogenesis, according to a new paper in Science Advances from biomedical engineer Nick Willett’s lab.

“These data have implications directly on bone healing and more broadly on wound healing,” Willett says. “In bone healing or grafting scenarios, physicians are often quite conservative in how quickly patients begin to load the repair site.”

Willett’s lab is part of both Emory’s Department of Orthopedics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and is based at the Atlanta Veterans Affairs Medical Center.

Former BME graduate student Marissa Ruehle was the first author of the paper. She and her colleagues investigated how mechanical strain affects angiogenesis, when microvascular fragments are cultured in a collagen hydrogel.

Apparatus for applying mechanical strain rhythmically — at a frequency that simulated walking

Courtesy of Nick Willett

Researchers applied pressure to the growing blood vessels (see photo) to a degree that created 5, 10 or 30 percent strain. The pressure, either early (0 to 5 days) or late (5 to 10 days), was applied rhythmically in a way that simulated walking. The Willett says he and his team expected — based on previous research – that 30 percent strain would be inhibitory to healing. Instead, the highest amount of strain pushed blood vessels to grow longer and branch more – but only when applied in the later stages.

“We originally hypothesized that 30 percent strain would be inhibitory both early and delayed, because it is such a large magnitude,” Willett says. “This finding highlights the differences in strain sensitivity between the early stage, when vessels are still forming, and more established networks.”

Ruehle and the other researchers were able to discern the effects of the mechanical strain on proliferation, and on the extracellular matrix – the mesh of proteins outside the cell. They also could take a peek at some of the genes whose activity was affected by high amounts of mechanical strain.

Experts say that modulating the timing of mechanical strain could be relevant for several scenarios of healing or regeneration, where rehabilitation such as a Post Rehab Fitness Program and mechanical therapy could be used to enhance repair.

“While we were initially motivated by bone tissue regeneration, a number of other tissues also experience ECM [extracellular matrix] forces; for example, ligaments and tends undergo tension, venous ulcers are often treated with compression bandages, and even cutaneous wounds experience tension during closure,” they write.