Surface heparinization and blood compatibility modification of small intestinal submucosa (SIS) for small-caliber vascular regeneration

Abstract

This study aims to investigate the small intestinal submucosal (SIS) surface after heparinization with the hypothermia plasma technique, to improve the blood compatibility of SIS, and to explore the possibility of construction of small-caliber vascular grafts with modified SIS scaffolds in vivo. SIS films prepared from jejunums of pigs were processed for surface treatment at different time periods with the argon plasma initiation technique under vacuum, and were then immediately immersed in 4% (m/v) heparin sodium solution for 24-h heparinization. The surface morphologies of heparinized SIS were observed under a scanning electron microscope (SEM). The antithrombogenicity of the modified SIS films was tested by measuring the water contact angle, blood coagulation time, activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and observation of platelet adherence by SEM. Heparinized SIS films were sewn into a small caliber (3-mm) tube and implanted into the defect of a canine femur by anastomosis as a vascular graft. The efficiency of the SIS graft was evaluated according to the patency for the circulation of blood with Doppler color ultrasonography and hematoxylin-eosin staining. Heparinized SIS showed a significantly different surface morphology compared with that of untreated SIS. The SIS surface resembles wrinkled film, but the heparinized SIS surface is uniformly coated with microdots, and appears to have a layer of heparin adhesion. Heparin was attached to the SIS surface after hypothermia plasma treatment. Hydrophilicity and antithrombogenicity of heparinized SIS were clearly increased. The heparinized SIS vascular graft showed great potential for replacement of defective small-caliber vessels.