Development of materials to release bioactive lipids

开发释放生物活性脂质的材料

• 批准号: 7133870
• 负责人: DONALD L ELBERT
• 金额: $ 37.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7133870
• 关键词: anticoagulants; antithrombogenic surface; bioengineering /biomedical engineering; biological signal transduction; biomaterial development /preparation; biomimetics; biotechnology; blood vessel prosthesis; cardiovascular pharmacology; carotid artery; cell adhesion molecules; cell migration; chemokine; clinical research; human tissue; medical implant science; peptides; phosphates; polyethylene glycols; slow release drug; sphingosine; surface coating; vascular endothelium

DESCRIPTION (provided by applicant): Bioactive lipids have emerged as critical factors in intra- and extracellular signaling. The bioactive lipid sphingosine 1-phosphate (S1P) elicits powerful responses from endothelial cells. The potent effects of S1P on endothelial cells suggest that controlled delivery of S1P may be beneficial in promoting the endothelialization of artificial materials. Unlike protein growth factors, S1P can be produced within materials enzymatically, from sphingosine that is already present in blood. We have previously synthesized polyethylene glycol materials that strongly resist protein adsorption and blood cell adhesion, but allow endothelial cell adhesion due to the presence of cell adhesion peptides. The materials function as an engineered mimic of the pseudointima that is associated with endothelialization in animals. However, our coatings will not promote coagulation and thrombosis and thus could be used as a coating for small diameter vascular grafts. In the proposed studies, we will characterize the new materials, the mechanism of S1P release and the effect of S1P delivery on cell adhesion and migration. The specific aims of this research project are: Aim 1: Demonstrate that S1P release kinetics are determined by the rate of diffusion of lipid-binding proteins through the hydrogel. Aim 2: Determine if controlled delivery of S1P allows the use of higher concentrations of RGD peptides in the PEG hydrogels, which may increase long-term cell adhesion strength. Aim 3: Demonstrate that enzymatic production allows delivery of S1P from nanoscale PEG coatings. Aim 4: Evaluate the safety and efficacy of S1 P-releasing PEG coatings containing RGD-peptide in the rat carotid artery.

描述（由申请人提供）：生物活性脂质已成为细胞内和细胞外信号传导的关键因素。生物活性脂质 1-磷酸鞘氨醇 (S1P) 可引起内皮细胞的强烈反应。 S1P 对内皮细胞的有效作用表明 S1P 的受控递送可能有益于促进人造材料的内皮化。与蛋白质生长因子不同，S1P 可以通过酶促方式从血液中已经存在的鞘氨醇中产生。 我们之前合成了聚乙二醇材料，该材料强烈抵抗蛋白质吸附和血细胞粘附，但由于细胞粘附肽的存在而允许内皮细胞粘附。这些材料作为与动物内皮化相关的假内膜的工程模拟物。然而，我们的涂层不会促进凝血和血栓形成，因此可以用作小直径血管移植物的涂层。 在拟议的研究中，我们将描述新材料、S1P 释放机制以及 S1P 递送对细胞粘附和迁移的影响。该研究项目的具体目标是： 目标 1：证明 S1P 释放动力学由脂质结合蛋白通过水凝胶的扩散速率决定。 目标 2：确定 S1P 的受控递送是否允许在 PEG 水凝胶中使用更高浓度的 RGD 肽，这可能会增加长期细胞粘附强度。 目标 3：证明酶促生产可以从纳米级 PEG 涂层中递送 S1P。目标 4：评估含有 RGD 肽的 S1 P 释放 PEG 涂层在大鼠颈动脉中的安全性和有效性。