Nanostructured surfaces with improved hemocompatibility

具有改善血液相容性的纳米结构表面

• 批准号: 10510050
• 负责人: Matthew Kipper
• 金额: $ 18.6万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-18 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10510050
• 关键词: Achievement; Acids; Address; Adhesions; Adsorption; Algae; Alkanesulfonates; Alloys; Antioxidants; Biocompatible Materials; Biological; Biopolymers; Blood; Blood Platelets; Blood Proteins; Blood Vessels; Blood coagulation; Cardiovascular system; Carrageenan; Catechols; Chemicals; Chemistry; Coagulation Process; Complement Activation; Complex; Corrosion; Data; Development; Devices; Endothelium; Erythrocytes; Evaluation; Event; Exhibits; Failure; Fibrin; Foreign Bodies; Healthcare; Heart Valve Prosthesis; Heart Valves; Hemorrhage; Heparin; Human body; Immune response; Implant; In Vitro; Inflammatory; Investigation; Leukocytes; Medical Device; Modernization; Modification; Molecular Conformation; Nanostructures; Plasma; Plasma Proteins; Platelet Activation; Polymers; Polysaccharides; Proanthocyanidins; Procedures; Property; Proteins; Research; Research Proposals; Resistance; Risk; Source; Stents; Sulfate; Surface; Thrombosis; TimeLine; Titania; Titanium; Whole Blood; Work; animal tissue; antimicrobial; base; biomaterial compatibility; carboxymethylation; common treatment; cost; experience; hemocompatibility; implantable device; improved; in vivo; in vivo evaluation; mechanical properties; nanoscale; novel; pathogen; prevent; recruit; response; restenosis; side effect; success; surface coating; thrombogenesis; water treatment

PROJECT SUMMARY/ABSTRACT: Blood-contacting medical devices, such as stents and heart valves, are common treatments in modern healthcare. Every year, approximately 1 million and 90,000 stent and prosthetic heart valve procedures are performed in the US, respectively. However, the use of these devices is associated with substantial risk of thrombosis, and the rate of failure due to clot formation can be as high as 6%. When whole blood plasma comes in contact with a foreign body (e.g., an implant), it leads to four main events capable of inducing a thrombogenic response in vivo: protein adsorption, platelet adhesion/activation, leukocyte recruitment, and further activation of complement and coagulation. Within seconds to minutes, key blood plasma proteins are adsorbed and undergo conformational changes on the surface. This layer of adsorbed protein will allow subsequent adhesion and activation of platelets, which promotes the formation of the fibrin clot, as well as the recruitment of leukocytes. The platelets then initiate an inflammatory immune response and promote a complex cascade of events resulting in thrombosis and/or fibrous encapsulation of the implant. Due to this complex foreign body response, hemocompatibility has been a significant issue for blood-contacting medical devices. To address this challenge, the development of novel biomaterials that can appropriately interact with blood and prevent thrombosis is vital for the success of many implantable devices. In this work, we propose to prevent thrombosis on implants by combining the promising properties of two biopolymers with nanoscale features on titania to develop a novel blood-compatible surface. Biopolymers are good candidates for these applications, because of their compatibility with the human body, biodegradability, processability and, in some cases, inherent antifouling and antithrombogenic properties. Our preliminary results indicate that carboxymethylation of kappa-carrageenan with monochloroacetic acid to form carboxymethyl-kappa-carrageenan (CMKC) improves the antithrombogenic properties. CMKC is chemically similar to heparin and prevents thrombosis through multiple mechanisms. However, CMKC is derived from algae, a renewable and low-cost source, while heparin is obtained from animal tissues. Moreover, CMKC does not cause the side effects that heparin presents, such as bleeding effects. Our group also has recently used of tanfloc (TA), a condensed tannin polymer as a biomaterial, and we have demonstrated its promising cytocompatibility, antioxidant activity, antimicrobial, and antifouling properties. Previous studies done by our group showed that the modification of titanium surfaces with TA and heparin decreased the blood protein adsorption/activation, and platelet adhesion and activation. This work aims to combine these promising properties of both biopolymers (CMKC and TA) to develop novel surfaces on titanium that can prevent thrombosis.

项目概要/摘要： 支架和心脏瓣膜等血液接触医疗器械是现代医学中常见的治疗方法 卫生保健。每年约有 100 万例和 90,000 例支架和人工心脏瓣膜手术 分别在美国进行。然而，使用这些设备会带来巨大的风险 血栓形成，因凝块形成而导致的失败率可高达 6%。当全血浆到来时 与异物（例如植入物）接触时，会导致四个主要事件，从而诱发血栓形成 体内反应：蛋白质吸附、血小板粘附/激活、白细胞募集以及进一步激活 补体和凝血。在几秒到几分钟内，关键的血浆蛋白被吸附并经历 表面构象变化。这层吸附的蛋白质将允许随后的粘附和 血小板的激活，促进纤维蛋白凝块的形成以及白细胞的募集。 然后血小板启动炎症免疫反应并促进一系列复杂的事件 植入物的血栓形成和/或纤维包封。由于这种复杂的异物反应， 血液相容性一直是血液接触医疗器械的一个重要问题。为了应对这一挑战， 开发能够与血液适当相互作用并防止血栓形成的新型生物材料至关重要 许多植入式设备的成功。在这项工作中，我们建议通过以下方式预防植入物上的血栓形成： 将两种生物聚合物的有前途的特性与二氧化钛的纳米级特征相结合，开发出一种新型 血液相容性表面。生物聚合物由于其兼容性而成为这些应用的良好候选者 与人体、生物降解性、加工性以及在某些情况下固有的防污和 抗血栓形成特性。我们的初步结果表明，κ-卡拉胶的羧甲基化与 一氯乙酸形成羧甲基-κ-卡拉胶 (CMKC) 可提高抗血栓形成能力 特性。 CMKC 的化学性质与肝素相似，可通过多种机制预防血栓形成。 然而，CMKC 来自藻类，这是一种可再生且低成本的来源，而肝素则来自动物 组织。此外，CMKC 不会引起肝素带来的副作用，例如出血效应。我们的 集团最近还使用 tanfloc (TA)，一种缩合单宁聚合物作为生物材料，我们有 证明了其有前途的细胞相容性、抗氧化活性、抗菌和防污特性。 本课题组前期研究表明，TA和肝素对钛表面的修饰 降低血液蛋白吸附/活化以及血小板粘附和活化。这项工作的目的是 结合两种生物聚合物（CMKC 和 TA）的这些有前途的特性，在钛上开发新型表面 从而可以预防血栓形成。