Novel surface-modified bioresorbable zinc-based stent materials

全世界每年大约植入500万个冠状动脉支架。大多数临床支架是由 不锈钢等耐腐蚀金属。然而，这些支架的终生存在往往不符合 预防并发症，包括支架内再狭窄(即动脉再狭窄)和晚期血栓形成(即 凝血)。可为冠心病患者提供终身治疗的替代品(如可生物降解材料) 封锁一直是人们寻求的目标。本文提出了一种新型的可生物可吸收的锌(锌)锶(锶)合金。 有希望成为支架的候选材料。强劲的初步结果证明了这一点的潜力和可行性 建议的研究。人们相信锌基支架植入后将不再需要二次手术。 并避免与目前的永久植入物相关的许多并发症。此外，与其他 可降解支架材料，即聚合物或镁(Mg)，具有合适配置的定制锌合金 更强的强度和延展性，更慢的降解与组织愈合的步伐相匹配，无氢进化 以及更好的生物相容性。锌本身是健康所必需的元素，而合金元素锶是一种营养。 还可以显著提高材料的力学性能和耐腐蚀性。这个项目的目标是 是为了确定新型二元锌锶合金的最有效成分，并测试它们作为 冠状动脉支架材料，在体外和体内，有三个特定的目的。目的1：制备表面修饰的锌粉 锶二元合金，使材料性能符合抗拉强度、伸长率的可接受值 失败，以及支架植入后的腐蚀率。植入物是通过熔融、轧制和挤压制备的， 用电子显微镜、X-射线衍射仪研究了材料的微观结构、物理性能和力学性能 衍射仪、原子发射光谱、拉伸和单轴压缩试验、浸泡试验和 目的2：系统评价种植体的体外生物相容性。 将对植入物进行蛋白质吸收、血液相容性、原代血管细胞活性和生长的检查， 血管干细胞的生长和分化，以及使用体外细胞模型直接内皮化。目标3： 利用大鼠动脉评价植入物的腐蚀性、安全性及其与体内血管组织的相互作用 植入模型。钢丝样品将被用来模拟支架支柱，其体内性能将被 在大鼠血管模型中进行了检测。将使用多普勒超声和显微CT来监测活体腐蚀 过程中，将进行组织学检查以评估炎症和免疫反应。

Approximately 5 million coronary stents are implanted world-wide each year. Most clinical stents are made of anti-corrosion metals such as stainless steels. Life-long presence of these stents, however, often falls short in preventing complications including in-stent restenosis (i.e. re-narrowing of arteries) and late thrombosis (i.e. clotting). Alternatives (e.g. biodegradable materials) that could deliver the life-long treatment for coronary blockade have long been sought. Here, a novel bioresorbable zinc (Zn)-strontium (Sr) alloy is proposed as a promising candidate for stent. Strong preliminary results demonstrated the potential and feasibility of this proposed study. It is believed that the Zn-based stent implants will eliminate the need for secondary surgeries and avoid many complications associated with current permanent implants. In addition, compared with other degradable stent materials, i.e., polymers or magnesium (Mg), tailored Zn alloys with right configuration offer stronger strength and ductility, slower degradation matching the pace of tissue healing, non-hydrogen evolution and better biocompatibility. Zn itself is an essential element for health while alloying element Sr is a nutrition element as well and can significantly enhance the mechanical and corrosion properties. The goals of this project are to determine the most effective compositions of novel binary Zn-Sr alloys and test their effectiveness as a coronary stent material, both in vitro and in vivo, in three specific aims. Aim 1: Prepare surface modified Zn- Sr binary alloys to tailor the material properties to accepted values of tensile strength, elongation to failure, and corrosion rate as stent implants. Implants are prepared by melting, rolling and extruding, and their microstructure, physical and mechanical properties are studied using electron microscopy, X-ray diffractometory, atomic emission spectrometry, tensile and uniaxial compression tests, immersion tests, and electrochemical tests, etc. Aim 2: Evaluate the biocompatibility of implants in vitro systematically. Implants will be examined on protein absorption, hemocompatibility, primary vascular cell viability and growth, vascular stem cell growth and differentiation, and direct endothelialization using in vitro cellular models. Aim 3: Evaluate implants corrosion, safety and interactions with vascular tissues in vivo using a rat arterial implantation model. Wire samples will be used to mimic the stent struts and their in vivo performances will be examined in a rat vascular model. Doppler ultrasound and microCT will be used to monitor the in vivo corrosion process, and histological examination will be performed to assess the inflammation and immune response.