Novel Engineered Particle Platform for Endothelium Regeneration

用于内皮再生的新型工程颗粒平台

• 批准号: 8788441
• 负责人: Kytai Truong Nguyen
• 金额: $ 36.59万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8788441
• 关键词: Adherence; Adhesions; Angioplasty; Animal Model; Area; Arteries; Binding; Biocompatible; Biocompatible Materials; Blood Circulation; Blood Platelets; Blood Vessels; Blood coagulation; CD34 Antigens; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Maturation; Cell Proliferation; Cell-Matrix Junction; Cells; Deposition; Development; Effectiveness; Endothelial Cells; Endothelium; Engineering; Evaluation; Family; Family suidae; Goals; Growth Factor; Healed; Health; In Situ; In Vitro; Inflammation; Injectable; Injury; Intervention; Investigation; Ligands; Modality; Nanotechnology; Natural regeneration; Nature; Obstruction; Outcome; P-Selectin; Peptides; Physiological; Play; Polyesters; Polymers; Population; Prevention; Procedures; Property; Rattus; Reagent; Recruitment Activity; Research; Research Project Grants; Role; Site; Smooth Muscle Myocytes; Solutions; Stem cells; Surface; System; Technology; Testing; Therapeutic; Thrombosis; Tissue Engineering; Toxic effect; Urethane; VWF gene; Vascular Diseases; Vascular Endothelium; Work; base; biomaterial compatibility; cardiovascular disorder therapy; cell motility; economic impact; healing; improved; in vivo; in vivo regeneration; injured; innovation; mimicry; nanoparticle; novel; overexpression; particle; percutaneous coronary intervention; prevent; repaired; restenosis; scaffold; vascular tissue engineering

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：尽管经皮冠状动脉介入（PCI）方式（例如血管成形术）通常被用作治疗心血管疾病的标准程序，这是美国第一名死亡原因，但它们具有许多局限性，包括后再生造血病和血栓形成。 PCI血管损伤后延迟的内皮再生已被认为是这些缺点的主要原因，尤其是晚血栓形成。实际上，内皮层是动脉的自然障碍，并且在预防血小板粘附和平滑肌细胞增殖和迁移中起着重要作用。因此，我们的长期目标是设计新型的多功能靶向纳米颗粒（MTN），该纳米颗粒（MTN）可以专门结合在受伤的动脉部位上，以作为临时障碍 在募集干细胞（例如内皮祖细胞（EPC））的同时，可以防止血小板粘附和平滑肌细胞迁移，以增强内皮再生。新颖的工程MTN将防止血小板粘附，并鼓励受伤部位的快速内皮愈合，从而可能原位重新内皮化。 为了实现我们的目标，提出了三个特定的目标：（1）合成并表征新型的可生物降解，生物相容性和与血液兼容的生物材料，包括氨基烷基掺杂的多酯（UPES），用于血管组织工程应用。 （2）制定由UPE组成的MTN，并带有包括生长因子在内的治疗试剂，并与受伤的动脉壁靶向配体和EPC结合分子共轭。将进一步研究MTN的各种特性，包括MTN对血小板沉积和体外内皮再生的影响。 （3）使用动物模型，在PCI损伤后，在体内新型MTN在体内再生的有效性。 这项研究有几个创新方面。根据组织工程和纳米技术的最新进展，我们的工程MTN提供了一种独特的策略，可以促进内皮再生，从而刺激PCI后刺激血管愈合的同时防止血小板粘附。我们研究的另一个新方面是，工程的MTN利用（1）靶向受伤的动脉的组合，（2）通过用作临时屏障来减少血小板的粘附，（（3）在靶向部位捕获EPC，在损坏区域间接减少损坏区域的血小板沉积，并使用（4）使用Endothephium Rementoffersementedshim innan nis nin nin nin。拟议的MTN将在PCI相关的血管损伤的治疗中取得重大改善，并在心血管疾病疗法中产生高度科学和经济的影响。