Improvement of blood compatibility of small intestinal submucosa used as engineering vascular scaffolds by nano-bionic surface modification

Abstract

To investigate the effects of nano-bionic surface modification in improving the blood compatibility of small intestinal submucosa (SIS) used as engineering vascular scaffolds. SIS films were obtained from pig and underwent nano-bionic surface modification with plasma initiation technique. Scanning electron microscopy (SEM) was used to observe the morphological features, including water contact angle, of the SIS films after nano-bionic surface modification. Modified SIS films were immersed into human platelet-rich plasma for 10 s and then observed for the adhesion of platelet on the surface thereof. Another modified SIS films were immersed into anticoagulant human blood to test the prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Twenty dogs were randomly divided into 2 equal groups to undergo cutting of bilateral femoral arteries and anastomosis with tube-like scaffolds made of modified or un-modified SIS films. Color Doppler ultrasonography was used to examine the blood flow 1, 3, and 6 weeks after operation. The dogs were killed in batches 2 and 6 weeks after operation to take out the SIS vessels to observe the existence of mural thrombus and undergo microscopy. SEM showed island-like and groove-like surface morphology in the modified SIS films, and the water contact angle decreased from 105.3 degrees to 62.0 degrees. After treatment by anticoagulant human blood the PT, APTT, and TT of the modified SIS films increased from 30.5 s, 9.8 s, and 13.6 s to 81.5 s, 39.6 s, and 50.2 s respectively. SEM showed that the number of adhering platelets was less on the surface of the modified SIS films than on the surface of un-modified SIS films. Animal experiment showed that 4 blood vessels anastomosed with un-modified SIS tube became completely thrombosed within 3 hours, and the other 6 became completely thrombosed 3 days later, and the 10 blood vessels anastomosed with modified SIS tube remained patent till 6 weeks after operation. Gross observation showed that the implanted scaffolds made of modified SIS films had become biological tube-like 2 weeks after operation, and became integrated tubes with their inner walls covered with endothelial cells 6 weeks post-operatively. Nano-bionic surface modified SIS film possesses good and persistent antithrombogenicity and shows excellent blood compatibility.