Nanostructured surfaces with improved hemocompatibility

具有改善血液相容性的纳米结构表面

基本信息

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
项目类别：
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

项目摘要

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：接触式医疗设备（例如支架和心脏瓣膜）是现代的常见治疗方法卫生保健。每年，大约有100万和90,000个支架和假肢心脏阀程序是分别在美国执行。但是，这些设备的使用与血栓形成，凝块形成造成的故障率可能高达6％。当全血等离学到来时与异物接触（例如植入物），它导致四个主要事件能够诱导血栓形成体内反应：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结。在几秒钟到几分钟之内，关键血浆蛋白被吸附并经历表面上的构象变化。这层吸附蛋白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，血小板发起炎症免疫反应，并促进一系列复杂的事件级联在血栓形成和/或植入物的纤维封装中。由于这种复杂的异物反应，对于血液接触医疗设备而言，血压相容性一直是一个重要的问题。为了应对这个挑战，可以适当与血液相互作用并预防血栓形成的新型生物材料的发展至关重要为了成功的许多植入设备。在这项工作中，我们建议通过将两种生物聚合物的有前途的特性与二氧化钛上的纳米级特征相结合，以发展出一种新颖血液兼容表面。生物聚合物是这些应用的好候选者，因为它们的兼容性具有人体，可生物降解性，可加工性，在某些情况下是固有的防污和抗巩膜的特性。我们的初步结果表明，Kappa-Carrageenan的羧甲基化单氯乙酸形成羧甲基 - 卡帕 - 卡拉甘丹（CMKC），改善了抗积体特性。 CMKC在化学上与肝素相似，并通过多种机制防止血栓形成。但是，CMKC衍生自藻类，藻类是可再生和低成本的来源，而肝素是从动物那里获得的组织。此外，CMKC不会引起肝素呈现的副作用，例如出血作用。我们的 Group最近还使用Tanfloc（TA），一种凝结的单宁聚合物作为生物材料，我们有证明了其有希望的细胞相容性，抗氧化活性，抗菌和抗污染物。我们小组进行的先前研究表明，用TA和肝素的钛表面修饰减少了血液蛋白吸附/激活，血小板粘附和激活。这项工作旨在结合两种生物聚合物（CMKC和TA）的这些有希望的特性，以在钛上发展新的表面这可以防止血栓形成。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
作者：
通讯作者：

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
作者：
通讯作者：

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
影响因子：
0
作者：
Dafu Wang;M. Hedayati;Julius D Stuart;L. Madruga;K. Popat;Christopher D. Snow;Mathew J Kipper
通讯作者：
Dafu Wang;M. Hedayati;Julius D Stuart;L. Madruga;K. Popat;Christopher D. Snow;Mathew J Kipper