Radioopaque resorbable polymers for vascular application

描述（由申请人提供）：由于在许多微创手术中，外科医生需要X射线引导系统来辅助植入物的正确放置，通过X射线摄影/荧光透视可见的可吸收聚合物代表了广泛未满足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。这种支架可以用作药物递送系统，并且可以避免金属支架刺激再狭窄的长期潜力。专注于这一特定应用，研究人员可以开始制定材料设计指南：机械强度要求、可调降解和再吸收曲线、X射线可见性、血液相容性以及与适合支架血管环境的细胞和组织的相互作用。基于这一基本原理，制定了一种设计策略，从而产生了一类新的生物材料，并针对血管应用进行了优化（AIM 1）。材料工作与试验模型的综合层次紧密相关，以研究细胞-材料相互作用，从简单的血液相容性试验，到在流动条件下使用异型共培养物，再到开发新的低成本啮齿动物模型，以有效评价体内试验材料（AIM 2）。AIMS 1和2的结果将是更好地理解血管生物材料的设计原则，这将指导选择有前途的聚合物用于可吸收的X射线可见支架。在AIM 3中，将通过制造功能性可展开支架原型来确认模型层次的预测值，将在可接受的家兔支架模型中测试其性能。在兔模型中以可接受方式运行的支架原型随后将在猪冠状动脉模型中进行临床前试验，该模型被广泛接受为人类临床结局的预测。通过这种方式，该研究项目将整合新生物材料的整个开发周期-然而，与首先合成聚合物并随后寻找应用的传统方法相反，该项目从定义的临床需求开始，并通过逻辑途径进行进展以满足这一需求。在理想的合作中，研究团队汇集了强大的生物材料跟踪记录（Kohn），临床输入（Nackman）和工业视角（Zeltinger）。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.