A novel intramural TGF β 1 hydrogel delivery method to decrease murine abdominal aortic aneurysm and rat aortic pseudoaneurysm formation and progression

Abstract

ObjectivesAneurysms are generally the result of dilation of all 3 layers of the vessel wall, and pseudoaneurysms are the result of localized extravasation of blood that is contained by surrounding tissue. Since there is still no recommended protocol to decrease aneurysm formation and progression, we hypothesised that intramural delivery of TGF β1 hydrogel can decrease aneurysm and pseudoaneurysm formation and progression. MaterialsMale C57BL/6 J mice (12–14 wk), SD rats (200 g) and pig abdominal aortas were used, and hydrogels were fabricated by the interaction of sodium alginate (SA), hyaluronic acid (HA) and CaCO3. MethodsA CaCl2 adventitial incubation model in mice and a decellularized human great saphenous vein patch angioplasty model in rats were used. TGF β1 hydrogel was intramurally delivered after CaCl2 incubation in mice; at day 7, the abdomen in some mice was reopened, and TGF β1 hydrogel was injected intramurally into the aorta. In rats, TGF β1 hydrogel was delivered intramurally after patch angioplasty completion. Tissues were harvested at day 14 and analysed by histology and immunohistochemistry staining. The pig aorta was also intramurally injected with hydrogel. ResultsIn mice, rhodamine hydrogel was still found between the medium and adventitia at day 14. In the mouse aneurysm model, there was a thicker wall and smaller amount of elastin breaks in the TGF β1 hydrogel-delivered groups both at day 0 and day 7 after CaCl2 incubation, and there were larger numbers of p-smad2- and TAK1-positive cells in the TGF β1 hydrogel-injected groups. In the rat decellularized human saphenous vein patch pseudoaneurysm model, there was a higher incidence of pseudoaneurysm formation when the patch was decellularized using 3% SDS, and delivery of TGF β1 hydrogel could effectively decrease the formation of pseudoaneurysm formation and increase p-smad2 and TAK1 expression. In pig aortas, hydrogels can be delivered between the medium and adventitia easily and successfully. ConclusionsIntramural delivery of TGF β1 hydrogel can effectively decease aneurysm and pseudoaneurysm formation and progression in both mice and rats, and pig aortas can also be successfully intramurally injected with hydrogel. This technique may be a promising drug delivery method and therapeutic choice to decrease aneurysm and pseudoaneurysm formation and progression in the clinic.