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Novel Zinc-Nanocomposite Materials for Pediatric Bioresorbable Cardiovascular Stents

用于儿科生物可吸收心血管支架的新型锌纳米复合材料

基本信息

批准号：
10450158
负责人：
Daniel Steven Levi
金额：
$ 42.92万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10450158
关键词：
Adult Affect Alloys Anatomy Animal Model Aorta Aortic coarctation Biological Process Blood Vessels Caliber Cardiovascular system Catheters Child Childhood Congenital Abnormality Congenital Heart Defects Coronary artery Corrosion Development Disease Elements Ensure Evaluation Failure Family suidae Fatigue Geometry Goals Growth Hyperplasia Impairment Implant In Vitro Infant Inflammation Intervention Knowledge Manufactured Materials Mechanics Metals Obstruction Operative Surgical Procedures Pediatrics Performance Pharmaceutical Preparations Platelet aggregation Polymers Property Pulmonary artery structure Radial Recording of previous events Research Rest Risk Serious Adverse Event Stenosis Stents Stress Structure Testing Thoracic Surgical Procedures Thrombosis Tissues Toxic effect United States Zinc artery occlusion artery stenosis base biomaterial compatibility clinical application combat congenital heart disorder cost design ductile improved in vivo lung pressure manufacturability mechanical properties melting metallicity minimally invasive nanocomposite nanoparticle neonate novel patient population pediatric patients restenosis therapy design

项目摘要

ABSTRACT Many infants with congenital heart disease are born with obstruction in the aorta (aortic coarctation) or in the pulmonary arteries. Options for adults with these severe vascular obstructions include medications, surgery, and catheter-based interventions such as stents. For pediatric patients that do not respond to medications, surgery posts increased risks, and stents are not recommended because growing children require stents that either grow with the child, or biodegrade after tissue remodeling, so that the developing tissues can grow with the rest of the body. Unfortunately, most bioresorbable stents (BRS) in the pipeline are polymer stents designed for coronary arteries. As such, these stents are too soft to handle aortic and pulmonary pressures, and too small. Bioabsorbable metals are an attractive alternative for BRS. Metals have a higher mechanical strength and toughness than polymers, and many have a proven history of biocompatibility in vivo. One such metal is zinc. As an essential element in basic biological functions, zinc is well tolerated by living tissues, and recent in vivo studies have demonstrated that zinc has a steady corrosion rate with no severe adverse events. Furthermore, zinc has greater elongation to failure than other commonly studied metals for stents – important for expandable stent deployment. These properties make zinc an excellent candidate for pediatric BRS. However, pure zinc is mechanically weak, and requires alloying to the increase its strength. Unfortunately, this often comes at the cost of other favorable properties, such as corrosion rate, ductility, and/or biocompatibility. Recently, reinforcing metallic materials with nanoparticles has demonstrated great potential as a strategy to significantly enhance mechanical properties. By using nanoparticle-dispersions, zinc’s mechanical properties can be improved significantly while retaining the favorable properties of zinc. Therefore, our hypothesis is that zinc-nanocomposites can be used to manufacture BRS suitable for pediatric applications that maintain sufficient structural integrity for 4-6 months before completely degrading into non-toxic byproducts. The development of a pediatric BRS fabricated using zinc-nanocomposite for the treatment of congenital heart disease will be achieved by pursuing the following aims: Aim 1 – Optimize zinc and nanoparticle combination to strengthen zinc-nanocomposite materials for manufacturing of functional pediatric BRS. Aim 2 – Characterize the biocompatibility, and mechanical properties of zinc- nanocomposites in vitro. Aim 3 – Assess in vivo efficacy and biocompatibility of zinc-nanocomposite stents in a rapidly growing pig animal model. The anticipated results will provide much needed guidance to further fine tune the core materials. Ultimately, a mechanically robust, biocompatible, and biodegradable stent has the potential to revolutionize the treatment of arterial obstructions in pediatrics patients by eliminating the need for open chest surgeries in infants and older children. Additionally, the knowledge gained from this research will have a broad impact on the development of safe and efficacious bioabsorbable metallic implants for many clinical applications.

摘要许多患有先天性心脏病的婴儿出生时就患有主动脉阻塞（主动脉缩窄）或肺动脉患有这些严重血管阻塞的成年人的选择包括药物治疗，手术，以及基于导管的介入，例如支架。对于对药物无反应的儿科患者，手术会增加风险，不推荐使用支架，因为成长中的儿童需要支架，要么与孩子一起生长，要么在组织重塑后生物降解，这样发育中的组织就可以与孩子一起生长。身体的其余部分。不幸的是，大多数生物可吸收支架（BRS）的管道是聚合物支架是为冠状动脉设计的因此，这些支架太软而不能处理主动脉和肺动脉压力，太小了生物可吸收金属是BRS的一种有吸引力的替代品。金属具有更高的机械强度在强度和韧性方面，许多聚合物都比聚合物更好，并且许多聚合物在体内具有经证实的生物相容性。一个这样金属是锌。作为基本生物功能中的必需元素，锌被活组织良好耐受，最近的体内研究已经证明锌具有稳定的腐蚀速率，没有严重的不良事件。此外，锌具有比其他通常研究的支架金属更大的断裂伸长率-重要的是用于可扩张支架展开。这些特性使锌成为儿科BRS的绝佳候选物。然而，纯锌的机械强度较弱，需要合金化来增加其强度。可惜这通常是以牺牲其它有利的性能如腐蚀速率、延展性和/或生物相容性为代价的。最近，用纳米颗粒增强金属材料已经显示出作为一种策略的巨大潜力，显著提高机械性能。通过使用纳米颗粒分散体，锌的机械性能在保持锌的良好性能的同时，因此，我们假设，锌纳米复合材料可用于制造适用于儿科应用的BRS，在完全降解为无毒副产物之前，保持足够的结构完整性4-6个月。的开发使用锌纳米复合材料制造的用于治疗先天性心脏病的儿科BRS 疾病将通过追求以下目标来实现：目标1 -优化锌和纳米颗粒的组合强化锌纳米复合材料，用于制造功能性儿科BRS。目标2 - 在体外表征锌纳米复合材料的生物相容性和机械性能。目标3 -评估锌纳米复合支架在快速生长猪动物模型中的体内功效和生物相容性。的预期结果将为进一步微调堆芯材料提供急需的指导。最终将其识别为机械坚固、生物相容和生物可降解的支架具有彻底改变治疗的潜力，通过消除婴儿和老年人开胸手术的需要，孩子此外，从这项研究中获得的知识将对发展产生广泛的影响，安全有效的生物可吸收金属植入物，可用于许多临床应用。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Highly Ductile Zn-2Fe-WC Nanocomposite as Biodegradable Material.

DOI：
10.1007/s11661-020-05878-y
发表时间：
2020-09
期刊：
Metallurgical and materials transactions. A. Physical metallurgy and materials science
影响因子：
0
作者：
Guan Z;Linsley CS;Pan S;DeBenedetto C;Liu J;Wu BM;Li X
通讯作者：
Li X

Zn-Mg-WC Nanocomposites for Bioresorbable Cardiovascular Stents: Microstructure, Mechanical Properties, Fatigue, Shelf Life, and Corrosion.

DOI：
10.1021/acsbiomaterials.1c01358
发表时间：
2022-01-10
期刊：
ACS BIOMATERIALS SCIENCE & ENGINEERING
影响因子：
5.8
作者：
Guan, Zeyi;Linsley, Chase S.;Pan, Shuaihang;Yao, Gongcheng;Wu, Benjamin M.;Levi, Daniel S.;Li, Xiaochun
通讯作者：
Li, Xiaochun

Enabling Smart Manufacturing Research and Development using a Product Lifecycle Test Bed.