Research Project
9345691
ABSTRACT Trauma is the 4th leading cause of morbidity and mortality after heart disease, malignancies, and lower respiratory illnesses in the United States. Blunt abdominal trauma (BAT) is commonly caused by vehicular accidents and falls. Uncontrolled bleeding is a major factor in early mortality after trauma, contributing to 30 to 40% of trauma-related deaths. Transcatheter arterial embolization (TAE) techniques play a significant role in the comprehensive modern treatment of traumatic vascular injuries to solid organs and extremities. Current embolic agents have proven to be problematical with regard to non-resorbability or unpredictable resorption, catheter clogging, or cytotoxicity due to the presence of organic solvents. Thus, there is a need for a new multi- potent embolic agent formulated with biocompatible components that addresses these issues to more effectively manage hemorrhage in trauma patients. The long-term goal is to obtain a simple, safe, and more effective treatment method for traumatic hemorrhage control after BAT. EmboMedics is developing a resorbable hydrogel that will improve clinical practice by providing an embolotherapeutic solution that is well-suited to a trauma care setting, being easy to mix and inject, self- crosslinkable, resorbable, nontoxic, and travelling distally from the site of injection. Preliminary data show that the hydrogel has an adjustable gelation time and resorption rate, is non-cytotoxic to endothelial cells and capable of occluding arteries, which is promising for hemorrhage control. Compared with Gelfoam, a commonly used embolic agent for trauma, this hydrogel would obviate the need for manual cutting to size prior to use. Compared to liquid local hemostatic agents such as N-butyl cyanoacrylate (super glue) and Onyx, the hydrogel is advantageous as it is easier to manipulate, resorbable, and non-cytotoxic. While not radiopaque, this novel hydrogel can be loaded with contrast to ensure visibility during embolization. Therefore, EmboMedics' hypothesis is that its novel hydrogel can serve as a naturally derived, nontoxic and completely biodegradable embolic agent that is more effective than existing agents for hemorrhage control. The objective of the proposed research is to validate the use of this novel hydrogel as an embolic agent for the control of internal bleeding that occurs with BAT. This project will evaluate the efficacy of the resorbable hydrogel in a porcine renal model (Specific Aim #1). This will be accomplished by creating a trauma model in the porcine kidney following an established procedure (Aim 1A). This will be used to test the efficacy of the hydrogel as compared to a non-resorbable embolic product, in hemorrhage control (Aim 1B). The long-term hemorrhage control and resorbability of the embolics will be evaluated over 10 weeks (Aim 1C). Necropsy and histopathological analysis of the tested kidneys will be performed to evaluate the extent of infarction, non-target embolization, hydrogel resorption, recanalization and tissue response (Aim 1D).
