So many different factors can cause heart attacks or strokes, and it’s scary to think how many risks there are. One of those risk factors is ischemia, a condition in which blocked or hardened blood vessels cut off blood supply to tissue, causing stroke, heart attack, or even gangrene or other frightening conditions. Ischemia is treatable with surgery, but that’s mostly helpful for larger blood vessels. When the condition occurs in smaller blood vessels or those that have been damaged by prior treatment, things get much more complicated.
Professor Christopher Chen of Boston University and Harvard’s Wyss Institute for Biologically Inspired Engineering has developed a new treatment along with his colleagues, Dr. C. Keith Ozaki, an expert in leg ischemia and a surgeon at Brigham and Women’s Hospital; and Dr. Joseph Woo, head of cardiothoracic surgery at Stanford University. Their research comes in the form of a 3D printed patch that allows for the growth of new blood vessels while avoiding the problems associated with other methods.
“Therapeutic angiogenesis, when growth factors are injected to encourage new vessels to grow, is a promising experimental method to treat ischemia,” said Chen. “But in practice, the new branches that sprout form a disorganized and tortuous network that looks like sort of a hairball and doesn’t allow blood to flow efficiently through it. We wanted to see if we could solve this problem by organizing them.”
The researchers designed two patches with endothelial cells: one where the cells were pre-organized into a planned architecture, and the other where the cells were injected at random. In vivo results showed that the patch with the pre-organized cells reduced the prevalence of ischemia, while the disorganized patch resulted in a tangled mess.
“This pre-clinical work presents a novel approach to guide enhanced blood flow to specific areas of the body,” said Dr. Ozaki. “The augmented blood nourishment provides valuable oxygen to heal and functionally preserve vital organs such as the heart and limbs.”
The patches were 3D printed on the microscale, with a size of 100 microns to allow for tiny blood vessels. To 3D print the patches at that scale, Chen turned to Innolign Biomedical, a company he helped to found. With Innolign’s help, he and his colleagues were able to quickly 3D print and test several patterns. 3D printing will also allow the researchers to scale the patches for testing in larger, more complex tissue environments and organisms.
“One of the questions we were trying to answer is whether or not architecture of the implant mattered, and this showed us that yes, it does, which is why our unique approach using a 3D printer was important,” said Chen. “The pre-organized architecture of the patch helped to guide the formation of new blood vessels that seemed to deliver sufficient blood to the downstream tissue. While it wasn’t a full recovery, we observed functional recovery of function in the ischemic tissue.”
The researchers will continue to work with the technology, scaling the patches up and trying different architectures to see if they can find one that works better.
“This project has been long in the making, and our clinical collaborators have been indispensable to the success of the project,” said Chen. “As a bioengineer, we were focused on how to actually build the patch itself, while the clinical perspective was critical to the design process. We look forward to continuing our partnerships as we move forward.”
The research has been documented in a paper entitled “3D-printed vascular networks direct therapeutic angiogenesis in ischaemia,” which you can access here. Authors include T. Mirabella, J.W. MacArthur, D. Cheng, C.K. Ozaki, Y.J. Woo, M.T. Yang and C.S. Chen.