Millions of patients suffer from coronary artery and peripheral artery disease - conditions caused by a blocked or narrowed artery. Surgeons implant vascular grafts to "bypass" the occluded portion and restore blood flow to the ischemic heart or limb. When possible, surgeons construct these vascular grafts from harvested segments of veins or arteries. But perhaps as many as 30% of patients lack suitable vessels for harvest. In these cases, surgeons resort to prosthetic grafts made from PET or PTFE. Prosthetic grafts fail more often than natural grafts, necessitating additional corrective surgeries. Tissue-engineered blood vessels are under development, but are expected to be expensive and supply-limited. The U.S. is already expected to spend $400B on coronary heart disease alone by 2030. The optimal solution for these patients would be at once safe, effective, and inexpensive.

We are developing an in situ tissue-engineered blood vessel. We fabricate resorbable polymeric scaffolds based on poly(glycerol sebacate) (PGS), a fast-degrading elastomer developed by Dr. Wang while he was at MIT. These scaffolds are implanted orthotopically without any cell seeding or drug/cytokine loading - eliminating the most time-consuming, difficult, and expensive steps of traditional tissue engineering. After implantation, host cells invade the scaffold, degrade the polymer, and remodel the conduit into a living artery-like structure. In effect, this strategy utilizes the host as the bioreactor.

This project is translationally oriented but informed by basic science. To push towards the clinic, we are fabricating human-sized grafts and testing them in large animal models. To better understand the cues that inform remodeling, we are systematically altering scaffold parameters, implant sites, and host disease states in small animal models. We greatly appreciate the help of our collaborators in vascular surgery, cardiothoracic surgery, nephrology, medical imaging, veterinary medicine, biomechanics, computational modeling, polymer chemistry, materials science, vascular biology, and developmental biology.