Development and Optimization of an Injectable Liquid-to-Solid Polymer Gelation System for Treatment of Large and Wide-Neck Intracranial Aneurysms

摘要

An intracranial aneurysm is an abnormal enlargement or pouch that forms from a weakened vessel segment in the brain. Often going unnoticed and untreated, these aneurysms can rupture and cause a sudden and catastrophic hemorrhagic stroke. Approximately 15% of patients die from an intracranial aneurysm rupture even before receiving medical attention and 25% of patients die despite medical treatment. Patients that survive typically suffer from various levels of morbidity such as neurological deficits. Thus, only one in four patients who suffer a ruptured intracranial aneurysm will fully recover. It is estimated that between 3 million and 6 million Americans have intracranial aneurysms, and approximately 30,000 people in the United States suffer a rupture event each year. There are a number of endovascular aneurysm treatment devices currently on the market, as well as a few more under investigation. However, all of these devices have significant shortcomings such as limited biocompatibility and efficacy that can potentially be addressed with a new device or devices. This proposal details the development of a novel liquid embolic (PPODA-QT) that quickly solidifies into a stable and biocompatible cast of any aneurysm shape and size. This material could provide surgeons with a novel approach for aneurysm treatment, especially for large and wide-neck aneurysms that current devices have limited efficacy in treating. Preliminary in vitro modeling and in vivo aneurysm studies have demonstrated that PPODA-QT allows for precise delivery control, vessel protection, and complete and durable occlusion of larger side-wall and bifurcation aneurysms with small-, medium-, and wide-necks, while eliminating the issues encountered with past liquid embolics like Onyx such as biocompatibility, device migration during delivery, and catheter adhesion. Gross and histological evaluation of PPODA-QT injected into in vivo aneurysm models has also suggested that the material is highly biocompatible, making PPODA-QT an exciting material candidate for endovascular intracranial aneurysm treatment.1.