Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China; Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Henan, China.
Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China.
Biomed Pharmacother. 2021 May;137:111296. doi: 10.1016/j.biopha.2021.111296. Epub 2021 Feb 3.
Aneurysms 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.
Male 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 CaCO.
A CaCl 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 CaCl 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.
In 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 CaCl 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.
Intramural 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.
动脉瘤通常是血管壁 3 层扩张的结果，假性动脉瘤是血液通过周围组织局部渗出而形成的。由于目前尚无减少动脉瘤形成和进展的推荐方案，我们假设向壁内递送 TGFβ1 水凝胶可以减少动脉瘤和假性动脉瘤的形成和进展。
雄性 C57BL/6 J 小鼠（12-14 周）、SD 大鼠（200 克）和猪腹主动脉被用于该研究，水凝胶是通过海藻酸钠（SA）、透明质酸（HA）和 CaCO3 的相互作用制备的。
在小鼠中使用氯化钙（CaCl）外膜孵育模型，在大鼠中使用去细胞化人大隐静脉补片血管成形术模型。在小鼠中用氯化钙孵育后，将 TGFβ1 水凝胶向壁内递送；在第 7 天，一些小鼠的腹部重新打开，将 TGFβ1 水凝胶向主动脉内壁内注射。在大鼠中，在补片血管成形术后向壁内递送 TGFβ1 水凝胶。在第 14 天采集组织，进行组织学和免疫组织化学染色分析。猪主动脉也被向壁内注射了水凝胶。
在第 14 天，在中层和外膜之间仍能发现罗丹明水凝胶。在小鼠动脉瘤模型中，在 CaCl 孵育后第 0 天和第 7 天，TGFβ1 水凝胶递送组的壁更厚，弹性蛋白断裂更少，TGFβ1 水凝胶注射组的 p-smad2 和 TAK1 阳性细胞数量更多。在大鼠去细胞化人隐静脉补片假性动脉瘤模型中，当补片用 3%SDS 去细胞化时，假性动脉瘤的形成率更高，而 TGFβ1 水凝胶的递送可以有效减少假性动脉瘤的形成，并增加 p-smad2 和 TAK1 的表达。在猪主动脉中，水凝胶可以很容易地和成功地在中层和外膜之间被递送到。
TGFβ1 水凝胶的壁内递送可以有效地减少小鼠和大鼠的动脉瘤和假性动脉瘤的形成和进展，猪主动脉也可以成功地被向壁内注射水凝胶。该技术可能是一种有前途的药物递送方法和治疗选择，可以减少临床中的动脉瘤和假性动脉瘤的形成和进展。
