Nanostructured surfaces with improved hemocompatibility

具有改善血液相容性的纳米结构表面

• 批准号: 10686166
• 负责人: Matthew Kipper
• 金额: $ 22.38万
• 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/10686166
• 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; Encapsulated; 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; Titania; Titanium; Whole Blood; Work; animal tissue; antimicrobial; biomaterial compatibility; carboxymethylation; common treatment; cost; experience; hemocompatibility; implantable device; improved; in vivo; in vivo evaluation; marine; mechanical properties; nanoscale; novel; pathogen; prevent; recruit; response; restenosis; side effect; success; surface coating; thrombogenesis; timeline; 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.

项目摘要/摘要： 接触血液的医疗设备，如支架和心脏瓣膜，是现代医学中常见的治疗方法。 医疗保健。每年，大约有100万和9万例支架和人工心脏瓣膜手术 分别在美国演出。然而，使用这些设备会有相当大的风险 血栓形成，血栓形成的失败率可高达6%。当全血浆到来的时候 在接触异物(例如，植入物)时，它会导致四个主要事件，能够诱发血栓形成 体内反应：蛋白质吸附、血小板黏附/激活、白细胞募集和进一步激活 补体和凝血。在几秒钟到几分钟内，关键的血浆蛋白被吸附并经历 表面的构象变化。这一层吸附的蛋白质将允许随后的黏附和 激活血小板，促进纤维蛋白凝块的形成，以及白细胞的募集。 然后，血小板启动炎性免疫反应，促进一系列复杂的事件，从而 在植入物的血栓形成和/或纤维包裹中。由于这种复杂的异物反应， 血液相容性一直是接触血液的医疗设备的一个重要问题。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防止植入物血栓形成 结合二氧化钛上两种具有纳米级特征的生物聚合物的良好性能开发出一种新型的 血液相容的表面。生物聚合物是这些应用的很好的候选者，因为它们的兼容性 与人体、生物降解性、可加工性，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，卡巴-卡拉胶的羧甲基化 单氯乙酸形成羧甲基卡拉胶(CMKC)增强抗血栓形成作用 属性。CMKC在化学上类似于肝素，通过多种机制预防血栓形成。 然而，CMKC来自可再生的低成本来源藻类，而肝素则来自动物 纸巾。此外，CMKC不会引起肝素存在的副作用，如出血效应。我们的 该集团最近还使用了单宁缩合聚合物单宁(TA)作为生物材料，我们已经 展示了其良好的细胞相容性、抗氧化活性、抗菌和防污性能。 我们课题组以前的研究表明，用TA和肝素修饰钛表面 减少血液蛋白的吸附/活化，降低血小板的黏附和活化。这项工作旨在 将这两种生物聚合物(CMKC和TA)的这些有希望的特性结合在一起，在钛表面开发新的表面 可以预防血栓形成的药物。

项目成果

Antifouling Behavior of Copper-Modified Titania Nanotube Surfaces.

• DOI: 10.3390/jfb14080413
• 发表时间: 2023-08-04
• 期刊: Journal of functional biomaterials
• 影响因子: 4.8

Expanding the Scope of an Amphoteric Condensed Tannin, Tanfloc, for Antibacterial Coatings.

• DOI: 10.3390/jfb14110554
• 发表时间: 2023-11-18
• 期刊: Journal of functional biomaterials
• 影响因子: 4.8

Ligand Presentation Inside Protein Crystal Nanopores: Tunable Interfacial Adhesion Noncovalently Modulates Cell Attachment.

• DOI: 10.1016/j.mtnano.2023.100432
• 发表时间: 2023-11
• 期刊: Materials today. Nano
• 作者: Dafu Wang;M. Hedayati;Julius D Stuart;L. Madruga;K. Popat;Christopher D. Snow;Mathew J Kipper