title: Murine ultrasound-guided transabdominal para-aortic injections of self-assembling type I collagen oligomers.
abstract: Abdominal aortic aneurysms (AAAs) represent a potentially life-threatening condition that predominantly affects the infrarenal aorta. Several preclinical murine models that mimic the human condition have been developed and are now widely used to investigate AAA pathogenesis. Cell- or pharmaceutical-based therapeutics designed to prevent AAA expansion are currently being evaluated with these animal models, but more minimally invasive strategies for delivery could improve their clinical translation. The purpose of this study was to investigate the use of self-assembling type I collagen oligomers as an injectable therapeutic delivery vehicle in mice. Here we show the success and reliability of a para-aortic, ultrasound-guided technique for injecting quickly-polymerizing collagen oligomer solutions into mice to form a collagen-fibril matrix at body temperature. A commonly used infrarenal mouse AAA model was used to determine the target location of these collagen injections. Ultrasound-guided, closed-abdominal injections supported consistent delivery of collagen to the area surrounding the infrarenal abdominal aorta halfway between the right renal artery and aortic trifurcation into the iliac and tail arteries. This minimally invasive approach yielded outcomes similar to open-abdominal injections into the same region. Histological analysis on tissue removed on day 14 post-operatively showed minimal in vivo degradation of the self-assembled fibrillar collagen and the majority of implants experienced minimal inflammation and cell invasion, further confirming this material's potential as a method for delivering therapeutics. Finally, we showed that the typical length and position of this infrarenal AAA model was statistically similar to the length and targeted location of the injected collagen, increasing its feasibility as a localized therapeutic delivery vehicle. Future preclinical and clinical studies are needed to determine if specific therapeutics incorporated into the self-assembling type I collagen matrix described here can be delivered near the aorta and locally limit AAA expansion.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States.
authors.forename: Alexa A
authors.initials: AA
authors.lastname: Yrineo
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States.
authors.forename: Amelia R
authors.initials: AR
authors.lastname: Adelsperger
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, United States.
authors.forename: Abigail C
authors.initials: AC
authors.lastname: Durkes
authors.affiliation: IU Health Center for Aortic Disease, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Distasi
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States; Department of Basic Medical Sciences, Purdue University, West Lafayette, IN, United States.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Voytik-Harbin
authors.affiliation: IU Health Center for Aortic Disease, Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States; Richard L. Roudebush VA Medical Center, Indianapolis, IN, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States; Center for Cancer Research, Purdue University, West Lafayette, IN, United States. Electronic address: cgoergen@purdue.edu.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Goergen
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000473:pathology; D024042:Collagen Type I / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000648:ultrastructure; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014463:Ultrasonography / Q000295:instrumentation
chemical_list: D024042:Collagen Type I