Friday, April 19, 2024
4/19/2024
Abstract Arteriovenous malformation (AVM) is an abnormal connection between an artery and a vein that bypasses the normal capillary circulation, often resulting in a tangle of vessels called a nidus. This abnormal connection causes high-pressure shunting of arterial blood directly to the venous circulation, placing excessive stress on the venous wall. Overstressed veins may enlarge, stretch, and eventually rupture leading to catastrophic bleeding. While AVMs can be congenital or traumatic in etiology, they can occur anywhere in the body (e.g., brain, spine, liver, pelvis and lung); however, they are associated with the highest morbidity and mortality when they occur in the central nervous system (CNS). For treatment, most patients are not surgical candidates for resection either because of comorbidities or it is deemed too risky to resect given the location of the AVM. In these patients, and in patients that present with acute bleeding, endovascular embolization is the preferred method of treatment. However, current FDA approved embolics are of the liquid type and they are only approved for use in the CNS prior to surgical resection to reduce bleeding risk during surgery. As a consequence, physicians are left in a position to use these liquid embolics off-label; they are used for embolization as the definitive treatment in those that cannot receive surgery and in those patients that present with acute bleeding. These liquid embolics (Onyx and Trufill) are far from perfect; they have recanalization rates of up to 36%, they are associated with leakage during injection that can cause non-target embolization, angiotoxicity and the possibility of necrosis. They are also challenging to deliver, they lack the universality to block wide range of vasculature sizes, they require lengthy pre-treatment prior to use (i.e., vortex for 30 min) and they lack intrinsic radiopacity for visualization on X-ray. Its administration requires more experienced operators as unpredictable polymerization may lead to nontarget embolization; even more concerning, the catheter can become entrapped within the polymerized embolic. While liquid embolics offer advantages over open-surgical repair, these drawbacks limit their widespread use. We hypothesize that by using a bioengineered gel embolic material (neuroGEM) that is non-toxic, durable (no recanalization), non- adhesive (avoiding catheter entrapment), and easier to use (hand-held injectable, no pretreatment, visible on X-ray), we would change the standard of medical practice. We aim to make a paradigm shift in the treatment of potentially fatal AVMs using a minimally invasive biomaterial-based platform to fill AVM vasculature using microcatheters with groundbreaking shear-thinning biomaterials. In Aim 1, we will develop neuroGEM compositions for effective AVM embolization. In Aim 2, we will evaluate the therapeutic effect of neuroGEM in rats. Finally in Aim 3, we will evaluate the performance of neuroGEM in vivo in porcine AVM model of embolization.
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