Murine Ultrasound-Guided Transabdominal Para-Aortic Injections of Type I Collagen

Abdominal aortic aneurysms (AAAs) are a potentially life-threatening disease that predominantly affect the infrarenal aorta. Several preclinical murine models that mimic the human condition have been developed and are now widely used to investigate AAA pathogenesis. Therapeutics designed to prevent AAA expansion are currently being evaluated using these animal models, but improvements in minimally invasive strategies for delivery could help in the translation of these therapeutics into the clinic. The purpose of this study is to investigate the use of self-assembling type I collagen oligomers as an injectable therapeutic delivery vehicle in mice. With the aid of noninvasive high frequency ultrasound, we describe the accuracy and reliability of an image-guided technique for murine para-aortic injections of collagen oligomers that quickly polymerize to form a collagen-fibril matrix at body temperature. Ultrasound-guided closed-abdominal injections successfully delivered collagen to the infrarenal abdominal aorta halfway between the right renal artery and aortic bifurcation into the iliac arteries. This minimally invasive approach proved to be similar to injections into the same region after opening the abdominal cavity. Finally, we observed minimal in vivo degradation of the self-assembled collagen over 14 days, further confirming this material’s potential as a method for delivering therapeutics. Future preclinical and clinical studies will be needed to determine if therapies incorporated into the self-assembling type I collagen matrix can effectively limit AAA expansion