Cardiovascular disease has been a leading cause of death worldwide. Although there have been many advances in the medial management and surgical treatment of cardiovascular disease, issues still arise due to the usage of synthetic materials. These complications typically are associated thromboembolic events such as stenosis and the lack of growth potential. Here we aim to improve upon the design of vascular grafts, and vascular implants in general, by developing a graft with a patterned and functionalized surface which we hypothesize will encourage cell proliferation and expansion across our biodegradable scaffold. As such, a tissue engineered vascular graft that has an endothelial cell monolayer covering the inside of the graft prior to implantation will mitigate problems such as stenosis due to endothelial cells modulating vascular homeostasis. Furthermore, the polymer scaffold will break down over time leaving the native tissue to take over the structural support of the implant and thus will allow for the implanted region to grow and develop with the individual.
Three aims are proposed to address this hypothesis: (1) in vitro testing and development of the patterned and functionalized substrates; (2) in vitro assessment of bioreactor seeding and expansion of hiPSC-derived ECs to form a monolayer on the vascular graft; and (3) in vivo assessment of the hiPSC-derived EC seeded vascular grafts. The goal of this project is to develop a patient-specific tissue engineering solution to problems with cardiovascular disease utilizing 3D printing technology and human induced pluripotent stem cells. We are, to the best of our knowledge, the first to 3D print luminal features on a vascular graft that can influence the phenotype and response of endothelial cells. The combination of 3D printing cues for cells in conjunction with hiPSCs can be used in many other applications and this approach would be a proof of concept while addressing a clinically relevant need. Additionally, this project will provide me with training necessary for my advancement necessary as an independent researcher. Research activities will be comprised mainly of research (80%), writing grant proposals and manuscripts, and meeting with my advisors (10%), advising undergraduates and graduate students and managing the laboratory (5%), and engaging in professional activities (5%).
Cardiovascular disease is a leading cause of death worldwide and many advances have been made in the medical management and surgical treatment of cardiovascular disease. However, there is still a need for an implant that can overcome the limitations currently plaguing synthetic implants. By developing an implant that uses both a stem cell line as a source of cells, that can potentially be used to derive patient-specific cells in th future, and a scaffold with cues to aid the survival and proliferation of the cells, we aim to overcome those challenges and improve patient care.
| Placone, Jesse K; Engler, Adam J (2018) Recent Advances in Extrusion-Based 3D Printing for Biomedical Applications. Adv Healthc Mater 7:e1701161 |
| Meng, Zhipeng; Qiu, Yunjiang; Lin, Kimberly C et al. (2018) RAP2 mediates mechanoresponses of the Hippo pathway. Nature 560:655-660 |
