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.
