Duke Clinical and Translational Science Institute has awarded $50,000 to an inter-institutional team of researchers investigating the possibilities of synthetic platelets for wound-healing processes.
Ashley Brown, PhD, and her team at the UNC & NC State Joint Department of Biomedical Engineering are developing new strategies for treating bleeding disorders as well as chronic nonhealing wounds through the use of nanoparticles that mimic the shape and other features of natural platelets in wound healing and coagulation. Most importantly, they’ve created particles that, like platelets, are able to augment the clotting process and retract clots, making them smaller and stabler.
Maureane Hoffman, MD, PhD, and her colleagues in the Duke Department of Pathology are studying the effects of hemophilia on wound healing. Even after bleeding stops, patients who have hemophilia are known to exhibit impaired wound healing. Their clots are not as strong, and they degrade quickly. The team’s hypothesis is that reduced thrombin generation results in poor platelet activation and impaired fibrin structure, causing the patients’ impaired healing.
In 2016, the two groups realized the potential of working together, and in early 2017, the CTSI Duke/NC State funding gave them the opportunity to make their collaboration official. Together, their goal is to apply platelet-mimetic particles to patients with hemophilia, enhancing functions of platelets that may lead to improved healing.
The potential implications of this project far outreach those affected by hemophilia. The group is also looking at impaired healing in the presence of oral anticoagulants; similar to hemophilia, oral anticoagulants negatively affect fibrin structure and may contribute to impaired wound healing.
Maureane Hoffman’s clinical specialty is blood banking. In the blood banking field, platelets are collected from normal donors, and the platelet concentrates have a very short shelf life. If a platelet alternative could be pulled off the shelf and given to patients, that would be a great advance in the blood banking field.
“The idea of being able to make platelets, rather than collecting them from an individual, and then being able to keep them stable until needed is a very big deal. It’s exciting to be involved.” - Hoffman
Synthetic platelets have been on researchers’ radars for a long time, but making it happen has proved difficult.
Although researchers have been interested in developing synthetic platelets for at least twenty years, their strategies for doing so have changed profoundly over the years. According to Brown, the biomaterial and nanotechnology realm has recently experienced a boom of interest and research in using nano- and micro-particles to create completely synthetic platelets. Synthetic platelet development before that consisted of natural platelets that had been freeze-dried. The cells are no longer alive, but they still are able to exhibit some of the function of fresh, natural platelets in clotting.
In the last several years, however, researchers have begun to focus on adding a binding element to nanoparticles that allows researchers to mimic certain aspects of platelet behavior. Distinctively, the Duke-NC State team wants to mimic the mechanics of platelets, too. Unlike many other approaches, these particles are malleable, and allow the particles to mimic the shape and texture of natural platelets.
“What’s amazing to me is that natural platelets have muscle fibers that contract to pull the edges of a wound together. It’s astonishing that putting the right binding proteins on synthetic platelets has allowed them to do that!” - Hoffman
The Duke Pathology members of the team focus on the cells that grow into the clot and replace it with new tissue. Their preliminary experiments have focused on a gel made out of collagen that should mimic skin tissue, which they plan to use to mimic wounds and test the platelet-mimetic particles.
The next step of the process is to develop a simple model of the wound-healing process that can be tested in a tissue-culture plate, before moving on to research that will involve live subjects and real wounds. Using CTSI funding, this phase will give the group the opportunity to define conditions and determine important factors before testing materials in any live animals.
The full research team on this project includes:
- Ashley Brown, PhD, assistant professor, UNC & NC State Joint Department of Biomedical Engineering
- Maureane Hoffman, MD, PhD, professor, Duke Department of Pathology, and director, Transfusion Service, Durham VA Medical Center
- Dougald “Mac” Monroe III, professor of medicine, UNC Division of Hematology/Oncology
- Seema Nandi, PhD student, UNC & NC State Joint Department of Biomedical Engineering
- Laura Sommerville, PhD, Post-doctoral researcher, Duke Department of Pathology
The Duke/NC State funding awards each institution up to $25,000 ($50,000 total) over a one-year period. The purpose of the award is to develop inter-institutional collaborations for new investigator teams conducting novel clinical and translational research that applies or accelerates discovery into testing in clinical or population settings. Proposals will be accepted again in spring 2018.
Publications supported in part or in full by the Clinical and Translational Science Award must cite the CTSA grant number, NIH grant UL1TR001117 and must be registered in PubMed Central.