1. Drug-Eluting Bioresorbable Polymer Scaffolding for Treatment of Aortic Aneurys

DESCRIPTION (provided by applicant): This proposal is focused on the development of a bioabsorbable polymeric scaffold intended to provide both time-release delivery of therapeutic agents as well as structural support in the treatment of aortic aneurysms.An abdominal aortic aneurysm (AAA) is a condition in which the aorta, the main blood vessel in the abdomen, expands like a balloon. The aneurysm weakens the wall of the aorta and can result in rupture. Because the volume of blood flowing through the aortais under relatively high pressure, a rupture can be catastrophic, resulting in death. Up to 75% of patients are asymptomatic prior rupture. In the United States, approximately one in every 250 people over the age of 50 will die of a ruptured aortic aneurysm. Aortic aneurysms affect as many as eight percent of people over the age of 65 and remains the 13th leading cause of death in the United States, accounting for more than 15,000 deaths each year. Research has shown that in the setting of AAA formation, the smooth muscle component of the arterial wall undergoes apoptosis and ceases to be mechanically relevant. The adventitia becomes thickened and assumes the role as the major load bearing component of the vessel wall. Overall, these results have lead us tosuggest that since the adventitia is the vulnerable component of the arterial wall in advanced AAA, that an outside-in therapy to mechanically and biologically stabilize the vessel wall may represent a more efficacious approach to aneurysm repair than those currently offered. MedShape Solutions has developed a series of bioabsorbable polymers capable of carrying various therapeutic agents. The proposed bioabsorbable polymeric scaffold will be developed to provide for the delivery of an agent to treat the aneurysmal tissue as well as provide structural support for the diseased portion of the aorta to prevent further expansion and/or rupture. In addition, the polymer chemistries under development are capable of in-situ polymerization which would allow theplacement of the scaffold around aortic segments that would normally be classified as having unfavorable anatomy and that might go untreated otherwise. Finally, the delivery system to be developed will be compatible with laparoscopic techniques which wouldmake it significantly less invasive than surgical repair. The aims of the Phase II proposal are to fundamentally investigate the polymeric scaffolding chemistry as it relates to mechanical characteristics as well as biodegradation and drug elution. In addition, the prototype delivery system for the drug/device combination will be finalized and evaluated in vivo in a 12 week large animal efficacy study. The primary research team will consist of Jack Griffis (PI), who is an expert in cardiovascular device development; Ken Gall PhD, a professor from Georgia Tech who specializes in polymers; and W. Robert Taylor, MD, a cardiologist from Emory University that specializes in AAA, as well as two other prominent vascular and cardiothoracic surgeons that will provide input into the surgical approach. PUBLIC HEALTH RELEVANCE: Abdominal aortic aneurysms (AAA) affect as many as eight percent of people over the age of 65 and remains the 13th leading cause of death in the United States, accounting for more than 14,000 deaths each year. In addition, for those who receive treatment, surgical revision rates are as high as 26% and up to 50% of those diagnosed are not eligible for the latest, minimally invasive techniques. This project will provide an approach that is both compatible with minimally invasive techniques as well as provide a means to reduce post-operative complications while delivering therapeutic agents directly into the aneurysmal tissue.