| 초록 |
Topic 1 for Stent coating: Cardiovascular disease is the number one cause of death worldwide. Stents are the most commonly implanted devices to effectively treat cardiovascular disease. However, bare metal stent (BMS) remains limited by relatively high rates of in-stent restenosis and the accompanying extracellular matrix deposition. Thus, drug-eluting stents (DES) have been developed to reduce restenosis. Although these efforts were successful, DES has its own set of shortcomings: late stent thrombosis, inflammation and delayed re-endothelialization. To address these issues, we developed a novel prohealing multifunctional stent coating: a nitric oxide (NO)-releasing endothelium-mimicking nanomatrix composed of the biomaterial- Peptide Amphiphile (PA). We evaluated the safety and efficacy of the novel coated stent in the rabbit iliac artery balloon injury model and compared with commercially available BMS and DES. The goal is to demonstrate the advantages of the nanomatrix coating which could enhance re-endothelialization, while reduce restenosis, inflammation, and thrombosis. We hypothesize that the prohealing multifunctional nanomatrix coated stent has several strengths compared with BMS and DES: 1) promoted re-endothelialization; 2) less restenosis than BMS; and 3) less inflammation and thrombosis than DES. Topic 2 for atherosclerosis model: Atherosclerosis is the main cause of cardiovascular disease. To evaluate therapeutics for treating atherosclerosis, in vivo and in vitro atherosclerosis models are developed. However, those atherosclerosis models have their own limitations. In vivo models, like pig and non-human primates, can develop lesions in coronary arteries, however, inducing atherosclerosis in them requires high cholesterol intake, long induction time, gene knock-out, and high expense. Although mouse models are the predominant models used in the labs, however, most of the currently mouse models show different plaque structure and genome from that of human. In vitro models are also used for evaluation due to their low cost; however, most of the those models are not generated following the pathogenesis of human atherosclerosis and are two-dimensional (2D) models which are limited to static culture in tissue culture plate and unable to provide three-dimensional (3D) tissue structures with proper functions. Thus, the main goal of this proposal is to develop an innovative biologically inspired 3D in vitro platform – tissue engineered atherosclerosis model (TEAM), featured with endothelial dysfunction, macrophages, and foam cells, following the pathogenesis of human atherosclerosis with low cost. |
