Douglas Hamilton anticipates the day when people with vascular disease (such as diabetics) will no longer fear that a simple wound will lead to horrible outcomes like amputation or even death.
“You and I don’t think anything about it; you get a cut on your leg and you know it’s going to heal,” said Hamilton, a Dentistry/Anatomy & Cell Biology professor. “But in a lot of incidents, for diabetics, and other people with vascular problems, is it doesn’t heal.”
Toward that goal, Hamilton and Dentistry/Engineering professor Amin Rizkalla, along with David Bagley of Advanced BioMatrix Inc., have received a Collaborative Health Research Projects grant to investigate new technologies in speeding the healing of skin wounds for vascular disease patients.
Their project, Novel technologies for engineering closure of non-healing skin wounds, recently received $697,970 over three-year term from the Canadian Institutes of Health Research (CIHR) and the National Science and Engineering Research Council (NSERC) partnered grant.
Most skin wounds close within a few days. For patients with vascular problems, however, those same wounds may stay open as long as 45 days, leading to the development of a chronic or non-healing wound. While commonly causing psychological and physical suffering, the condition can result in limb amputation and even death.
Despite extensive research, reproducible treatments for these wounds remain elusive.
“The technologies for treatment haven’t moved on though. It’s a huge clinical problem that tends to slip under the radar all the time,” Hamilton said. “We’ve been working on the scaffold for a while. The problem you have with these wounds is, they are stuck in a prone inflammatory phase and will not come out of it.”
Skin is composed of many different protein types, which change when skin is injured. Proteins, such as collagen, provide structural support. But another type, known as matricellular proteins, are produced in the wound bed and form a scaffold that cells attach to and move on.
These matricellular proteins are not normally present in the body but are upregulated after injury to provide cells instructions on how to repair the affected tissue.
Hamilton’s analysis of chronic wounds has found that two of these matricellular proteins – periostin and connective tissue growth factor (CCN2) – are missing and no scaffold is formed in the wound, meaning it is unable to repair.
“Our scaffold contain the proteins. If the body won’t produce them, we put them back in,” Hamilton said.
A sponge form of the scaffold not only increased wound closer time in diabetic mice by five-to-10 times, it also increased blood vessel growth.
With a multi-disciplinary collaborative research team consisting of biologists, engineers, imaging specialists, a veterinarian, clinicians and industrial collaborators, Hamilton said the recent grant will allow his team to look at ways to enhance the scaffold through improved cell infiltration, changing its parameters, perhaps the use of synthetic polymers and how to better maintain its bio-activity.
The ultimate goal is a full pre-clinical trial.
Co-investigators on the project include Maria Drangova (Medical Biophysics); Luc Dubois (Surgery, Epidemiology & Biostatistics); Alexander El Warrak (ACVS); Andrew Leask (Schulich); and Geoff Pickering (Medical Biophysics).
