Radioopaque resorbable polymers for vascular application

描述(申请人提供)：由于在许多微创手术中，外科医生需要X射线引导系统来帮助正确放置植入物，因此X射线摄影/透视可见的可吸收聚合物是满足各种未得到满足的临床需求的重要平台，其中最重要的是对可吸收、X射线可见冠状动脉支架的需求。这种支架可以作为药物输送系统，并可能避免金属支架刺激再狭窄的长期潜力。着眼于这一具体应用，研究人员可以从制定材料设计指南开始：对机械强度、可调降解和吸收曲线、X射线可见性、血液相容性以及与细胞和组织的相互作用的要求，这些要求适合支架的血管环境。基于这一原理，已经制定了一种设计策略，该策略导致了一类新的生物材料，针对血管应用进行了优化(目标1)。材料的工作一直与研究细胞-材料相互作用的测试模型的集成层次紧密相连，范围从简单的血液相容性测试，到在流动条件下使用异型共培养，再到开发一种新的、低成本的啮齿动物模型，用于体内测试材料的有效评估(AIM 2)。AIMS 1和2的成果将是更好地理解血管生物材料的设计原则，这将指导选择用于可吸收X射线可见支架的有前景的聚合物。在AIM 3中，模型层次的预测价值将通过制造功能性的、可展开的支架原型来验证，其性能将在公认的兔支架模型中进行测试。在兔模型中表现良好的支架原型随后将在猪冠状动脉模型中接受临床前测试，这被广泛认为是对人类临床结果的预测。通过这种方式，这一研究项目将整合一种新生物材料的整个开发周期--然而，与先合成聚合物然后寻找应用的传统方法相反，该项目从明确的临床需求开始，并通过一条逻辑路径来解决这一需求。在理想的合作中，研究团队将强大的生物材料记录(Kohn)、临床投入(Nackman)和产业视角(Zeltinger)结合在一起。制造和测试全功能支架原型以验证设计方法的能力是该项目的独特优势。

DESCRIPTION (provided by applicant): Since in many minimally invasive procedures the surgeon requires an X-ray guidance system to assist with the proper placement of an implant, resorbable polymers that are visible by X-ray radiography/fluoroscopy represent an important platform for a wide range of unmet clinical needs, the most significant of which is the need for resorbable, X-ray visible coronary stents. Such stents can serve as drug delivery systems and may avoid the long-term potential of metal stents to stimulate restenosis. Focusing on this specific application allows the investigators to begin with formulation of material design guidelines: the requirement for mechanical strength, tunable degradation and resorption profiles, X-ray visibility, blood compatibility, and interactions with cells and tissues that are appropriate for the vascular environment of a stent. Based on this rationale, a design strategy has been formulated that leads to a new class of biomaterials, optimized for vascular applications (AIM 1). The materials effort has been tightly linked to an integrated hierarchy of test models to study cell-material interactions ranging from simple tests of hemocompatibility, to use of a heterotypic co-culture under flow, to the development of a new, low cost rodent model for the efficient evaluation of test materials in vivo (AIM 2). The outcome of AIMS 1 and 2 will be a better understanding of the design principles for vascular biomaterials which will guide the selection of promising polymers for use in a resorbable, X-ray visible stent. In AIM 3, the predictive value of the hierarchy of models will be validated by the fabrication of functional, deployable stent prototypes whose performance will be tested in an accepted rabbit stent model. Stent prototypes that perform in an acceptable manner in the rabbit model will then be subjected to preclinical testing in the pig coronary artery model which is widely accepted as predictive of the human clinical outcome. In this way, this research project will integrate the entire development cycle for a new biomaterial - however, contrary to the conventional approach of synthesizing a polymer first and looking for an application later, this project starts with a defined clinical need and progresses through a logical pathway to address this need. In an ideal collaboration, the research team brings together a strong biomaterials track record (Kohn), clinical input (Nackman), and an industrial perspective (Zeltinger). The ability to fabricate and test fully functional stent prototypes for validation of the design approach is a unique strength of this project.