Engineered tissues have long been considered an exciting alternative source of small diameter vascular grafts owing to issues with the supply and patency of available alternatives. However, current research has not been sufficient to push this technology into the realm of clinical application. This is due to an insufficient understanding of the growth and remodeling of engineered tissue vascular grafts (ETVG) during in vitro incubation and after in vivo implantation. In this study we will evaluate the hypothesis that the compositional and mechanical properties of ETVGs can be manipulated via dual mechanical stimulation during incubation to drive the inflammatory foreign body reaction (FBR) towards the wound healing phase in vivo.Specifically, we aim to: (1) obtain ETVGs of varying mechanical properties but similar organization to native vasculature in dual mechanical stimulation environments and (2) demonstrate that ETVG properties gained through dual mechanical stimulation can be used to drive the in vivo inflammatory FBR towards the wound healing phase.Upon implantation an ETVG inevitably initiates a host response known as the foreign body reaction (FBR) that usually results in chronic inflammation causing fibrotic tissue formation and ultimately graft failure. However, some studies have shown that the severity FBR is affected by the stiffness of the target it acts upon. It is known that mechanical stimuli affects gene expression in vascular smooth muscle cells regulation proliferation, extracellular matrix synthesis, and structural adaptations which are all factors that determine ETVG mechanical properties. The process of ETVG growth and remodeling is mechano-driven as well as immune-mediated, and both aspects can be exploited to enhance the viability of ETVGs. Significance. Coronary artery bypass surgery (CABG) remains one of the most common cardiac surgical procedures performed worldwide. In addition to relieving supply limitations associated with CABG, ETVGs are especially ideal for pediatric patients who require grafts that grow as they do, eliminating the need for recurrent invasive surgeries.
|Program type||Predoctoral Fellowship|
|Effective start/end date||01/01/2020 → 12/31/2021|