Novel Engineered Particle Platform for Endothelium Regeneration

尽管经皮冠状动脉介入治疗（PCI）方式如血管成形术通常被用作治疗冠状动脉疾病的方法。 治疗心血管疾病（美国第一大死因）的标准程序，他们 具有许多局限性，包括晚期再狭窄和血栓形成。延迟内皮再生 经皮冠状动脉介入治疗引起的血管损伤被认为是这些缺点，尤其是晚期血栓形成的主要原因。 事实上，内皮层作为动脉的天然屏障，在动脉粥样硬化中起着重要作用。 防止血小板粘附和平滑肌细胞增殖和迁移。因此，我们的长期目标是 设计新型多功能靶向纳米颗粒（MTN）， 动脉部位作为临时屏障，以防止血小板粘附和平滑肌细胞迁移， 募集干细胞如内皮祖细胞（EPCs）以增强内皮再生。的 新的工程MTN将防止血小板粘附并促进损伤处的内皮快速愈合 部位，允许原位再内皮化的潜力。 为了达到我们的目标，提出了三个具体的目标：（1）合成和表征新的 生物可降解、生物相容性和血液相容性生物材料，包括掺杂染料的聚酯（UPE） 用于血管组织工程应用。(2)为了制定由UPE制成的MTN， 治疗试剂包括生长因子，并与损伤的动脉壁靶向结合 配体和EPC结合分子。MTN的各种性质，包括MTN对血小板的影响 将进一步研究体外沉积和内皮再生。(3)为了确定有效性 使用动物模型，在PCI损伤后，使用新型MTN进行体内原位内皮再生。 这项研究有几个创新的方面。我们的工程MTN，基于 组织工程和纳米技术的最新进展，提供了一个独特的战略，以促进 内皮再生，并因此刺激PCI后的血管愈合，同时防止血小板粘附。 我们研究的另一个新方面是，工程MTN利用（1）靶向 损伤的动脉，（2）通过作为临时屏障减少血小板粘附，（3）在血管壁捕获EPC， 靶向部位，其间接减少受损区域上的血小板沉积，以及（4）促进 使用工程组织纳米支架进行内皮再生。建议的中期票据将带来大量 改善PCI相关血管损伤的治疗，并应产生高度科学和 心血管疾病治疗的经济影响。

Although percutaneous coronary intervention (PCI) modalities such as angioplasty are often used as the standard procedure for treatment of cardiovascular disease, the number one cause of death in the U.S., they have many limitations including late restenosis and thrombosis. Delayed endothelium regeneration after vascular injury by PCI has been indicated as a major cause for these drawbacks, especially late thrombosis. Indeed, endothelium layer serves as a nature barrier for the artery and plays an important role in the prevention of platelet adhesion and smooth muscle cell proliferation and migration. Thus our long-term goal is to engineer novel multifunctional targeting nanoparticles (MTNs) that can bind specifically onto the injured arterial site to serve as a temporary barrier to prevent platelet adhesion and smooth muscle cell migration while recruiting stem cells such as endothelial progenitor cells (EPCs) for enhancing endothelium regeneration. The novel engineered MTNs will prevent platelet adhesion and encourage rapid endothelium healing at the injured site, allowing the potential of re-endothelialization in situ. To reach our goal, three specific aims are proposed: (1) To synthesize and characterize novel biodegradable, biocompatible, and hemo-compatible biomaterials including urethane-doped polyesters (UPEs) for vascular tissue engineering applications. (2) To formulate MTNs, which are made of UPEs, loaded with therapeutic reagents including growth factors, and conjugated with both the injured arterial wall targeting ligands and the EPC binding molecules. Various properties of MTNs including the effects of MTNs on platelet deposition and endothelium regeneration in vitro will be further investigated. (3) To determine the effectiveness of novel MTNs in vivo for endothelium regeneration in situ following PCI injury using animal models. There are several innovative aspects associated with this research. Our engineered MTNs, based on recent advances in both tissue engineering and nanotechnology, provide a unique strategy to promote endothelium regeneration and hence to stimulate vascular healing after PCI while preventing platelet adhesion. Another novel aspect of our research is that the engineered MTNs utilize the combination of (1) targeting injured arteries, (2) reducing platelet adhesion by serving as a temporary barrier, (3) capturing EPC at the targeted sites, which indirectly reduce platelet deposition on the damaged areas, and (4) promoting endothelium regeneration using engineered tissue nanoscaffolds. The proposed MTNs will bring in a significant improvement in the treatment of PCI-associated vascular injury and should generate highly scientific and economic impacts in cardiovascular disease therapy.