Weaving a Silk-Based Partnership
Vorp receives a 5-year, $3.5 million NIH Bioengineering Partnerships with Industry (BPI) grant
A luxurious fabric like silk is typically known for its fashionable properties, but thanks to one researcher at the University of Pittsburgh, its threads may have groundbreaking uses in regenerative medicine as well.
David Vorp, the John A. Swanson Professor of Bioengineering at Pitt’s Swanson School of Engineering, just received a 5-year, $3.5 million Bioengineering Partnerships with Industry (BPI) grant from the NIH for his project “Clickable Extracellular Vesicles to Silk-Based Biomaterials for Regenerative Medicine.” Vorp also serves as Senior Associate Dean for Research & Facilities.
BPI grants aim to support targeted technological development projects through strategic partnerships between academia and industry. One of only five currently activated BPI awards in the country, this NIH funding allows Vorp’s team to collaborate with industry partner RoosterBio, Inc., which propels commercialization of therapeutic technologies.
Making Silk “Click”
Regenerative medicine approaches require harnessing the appropriate cell signals at the right time and place to direct host tissue functions.These signals are often informed by mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs), which are like cell-to-cell communicators. While silk has been previously used in regenerative medicine research, it’s never been shown to bind with EVs.
“Silk has never been modified to latch on to extracellular vesicles.” Vorp said. “The first part of our grant is going to be geared towards us testing the idea of linking our EV’s to silk and showing that they do not change their regenerative properties as a result of that process.”
To bind silk and EV’s, Vorp will be collaborating with Co-PI Phil Campbell and Co-Investigator Charlie Ren, both professors in Carnegie Mellon University’s Biomedical Engineering Department, to use “click chemistry,” a chemical process that functions similarly to Velcro®.
“We published a paper about two years ago using bioorthogonal labeling and click chemistry to improve the retention of EVs inside collagen biomaterials so that we can achieve a long lasting effect,” Ren said. “In this project, we're very excited to apply this technology to functionalize silk and evaluate its regenerative capacity.”
The team is already working with Vorp to use EVs and click chemistry to treat abdominal aortic aneurysms through a Collaborative Sciences Award from the American Heart Association (AHA), but the applications in this project differ.
“The click chemistry process will allow us to keep the EV’s in place where they're needed for regenerative purposes,” Vorp said. “Two key differences between this BPI project and the AHA grant are that RoosterBio is part of the BPI research team, and the AHA grant is focused on treating aortic aneurysms, while the BPI project will develop and test the silk and EV conjugation then evaluate them in two different, demonstrative applications.”
Once the process to attach EVs to silk is worked out and validated, the team aims to demonstrate that this technology can be used in both a wound healing application and a tissue engineered vascular graft application. The vascular graft application could lead to new alternatives for coronary and other bypass grafting procedures, and the wound healing application could lead to new treatments that treat patients’ non-healing sores and wounds.
“Even just a simple blister on the foot or a small cut can turn into a problem for some diabetic or bedridden patients,” Vorp said. “There are different types of approaches that have been tried over the years, but nothing on the market right now is completely effective. We believe that a regenerative approach where we're stimulating the patient's own tissues and cells within the wound bed could change that.”
Manufacturing Success
Collaborating with RoosterBio is essential for this project to eventually produce a commercialized medical product. The company will incorporate the project’s azide labeling technology into an optimized manufacturing process using translation-ready stem cells, cell culture media production technology, and scalable upstream and downstream process expertise, according to RoosterBio CEO Tim Kelly.
“Extracellular vesicles have an increasing number of uses across regenerative medicine, but there are challenges in mode application, downstream processing, and manufacturing scale.” Kelly said. “By addressing key bottlenecks in large scale production, this project has potential to solve challenges in wound healing and targeted delivery in vivo.”
Not only could this technology offer improved wound care or vascular grafting for patients, but with the help of RoosterBio, it could also make treatment easier for clinicians as well. Since no cells are involved with the process, Vorp envisions that the product could be made in advance and shipped directly to operating rooms for ease of treatment.
“We envision that either the actual graft or the actual wound dressing can be made ahead of time, shipped out to operating rooms, and then it can be pulled off the shelf by surgeons when needed.” Vorp said.
Ultimately, this collaboration between Vorp’s team at Pitt, Campbell and Ren at CMU, and RoosterBio may allow for EVs to be widely available and easy to use for downstream consumers, including those that are advancing regenerative medicine.
“We’ve worked with Dr. Vorp’s team for several years, and we are excited to make an immediate impact in enabling a focus on their technology while RoosterBio lends its expertise in EV manufacturing and analytics, " Kelly said. “Long-term, our relationship and specific project will help us fuel the rapid implementation of scalable advanced therapies to ultimately support this technology for a broad market.”
RoosterBio accelerates human mesenchymal stem/stromal cell (hMSC) and extracellular vesicle (EV) product and process development to fuel the rapid implementation of scalable advanced therapies. Our high-quality hMSCs, bioprocess media, genetic engineering tools, and EV production solutions are paired with expert bioprocessing knowledge to progress therapeutic developers from concept to first-in-human testing and commercial manufacturing at reduced cost and increased productivity. With optimized, scalable processes, Type 2 Master Files, and cGMP products, we have enabled therapeutic programs to traverse their path to clinical translation in under 1 year. RoosterBio is driven by clients’ success and creating a world where safe and effective regenerative medicines are rapidly developed and widely available on a global scale.