3D Printed Pro-healing Vascular Stent Promoting Endothelizaton

Over 200 million people with atherosclerotic peripheral artery disease (PAD) worldwide are still suffering from considerable complications following endovascular interventions such as the placement of a stent. Although the advent of metallic drug eluting stents (DES) effectively reduces the restenosis rates to < 10%, the permanent presence of the stent hamper normal vasomotion, limit adaptive arterial remodeling, and can provoke long term foreign body responses. Polymeric bioresorbable vascular scaffolds (BVS) have emerged as a potential solution to these problems by providing initial vessel support to prevent recoil and slowly degrading to eliminate residual foreign materials and eventually restore vessel function. However, current BVS is still associated with the delayed arterial healing, i.e. a lack of functional endothelium recovery, leading to the high incidence of late thrombosis (3.5% at 2 years) and major adverse cardiac events (11% at 2 years). We propose to develop a pro-healing polymeric BVS for promoting endothelium regeneration and improving their clinical outcomes. Recent research efforts including ours develop many surface modification strategies such as topographic patterning and stiffness control for promoting functional endothelium regeneration. Yet their clinical translation is largely hampered due to the lack of effective technologies for engineering surface properties in three-dimensional (3D) scaffolds. In this study, we will utilize a 3D printing technology to fabricate a clinically relevant polymeric BVS while achieving in-process control of topographic patterns and local stiffness for promoting endothelium regeneration. Specially, we will: 1) fabricate and optimize the luminal pattern and stiffness of 3D-printed BVS for promoting endothelium regeneration through in vitro evaluation; and 2) assess the endothelium regeneration and performance of 3D-printed BVS in a rabbit model. I have assembled a multi-disciplinary mentoring team to provide me complementary training in polymer science and vascular translational medicine (Ameer) and additive manufacturing (Sun). Overall, We strongly believe that this award will advance my long-term career goal, which are to establish an independent, internationally recognized research program focusing on the design and manufacturing of biomaterials for vascular regenerative engineering and to ultimately translate my research product into clinical use for improving the PAD treatments.