动物造模,药效评价,心脏瓣膜 z-bio 2024-09-18 395

　　Heart valve disease is an important disease that endangers human health, and the main treatment method is heart valve replacement surgery. At present, the commonly used valve substitutes for clinical treatment of heart valve disease are mechanical valves and biological valves. With the rapid development of biotechnology, tissue engineering heart valves have become a hot topic in the field of heart valve surgery as a potential ideal artificial heart valve. The ideal tissue-engineered valve is made of biodegradable materials as scaffolds, with autologous cells implanted onto the scaffold material. As the tissue-engineered valve undergoes self remodeling and renewal, it gradually becomes the patient's own valve. However, it has been found in experimental research that the adhesion between seed cells and scaffold materials remains an unresolved issue. Subsequently, researchers proposed a generalized theory of tissue-engineered valves, which utilizes animal heart valves as scaffold materials. Pig aortic valve and human heart valve have similar anatomical structure and tissue morphology. The decellularized natural valve stent retains the intact extracellular matrix structure and function, providing an important microenvironment for cell adhesion and growth. At the same time, it also has good biomechanical properties and is an important scaffold material for constructing tissue-engineered heart valves.

　　Early studies that treated pig heart valves with anti immune rejection or applied them directly after decellularization resulted in failure. For example, Schreiber et al. reported a clinical trial of pig pulmonary artery catheters (SPVC) treated with Shelhigh No React (NR-4000PA series). They planned to implant SPVC of different specifications into 34 patients from May 2004 to May 2005. However, after completing 15 catheter implantations in 13 patients, the continuation of implantation was temporarily cancelled due to the observation of many early failures. Although only 2 patients died and it was not due to reasons related to catheter implantation, they found that this treated pig heart valve had extensive pseudointimal detachment and chronic rejection reactions after implantation, resulting in varying degrees of catheter stenosis. Therefore, they believe that this small-sized SPVC is not an ideal material for right ventricular outflow tract (RVOT) reconstruction.

　　Researchers from Cryolife in the United States used healthy pig heart valves as raw materials, removed cellular components that may cause immune rejection reactions with chemical drugs, and implanted them into recipients. They called this decellularized pig valve Synergrafl valve. In animal experiments and clinical applications in adult patients, this valve stent structure grows well and is covered by autologous endothelial cells. However, severe immune rejection reactions occurred during application in pediatric patients, resulting in the tearing and decay of implanted valves, and leading to the death of three patients, forcing the discontinuation of the Synergraft valve in clinical practice.

　　The decellularized pig heart valve was used as a scaffold, and tissue engineering endometrial coating was performed, achieving good results. Schirali et al. reviewed and analyzed the efficacy of Carpentier EdwardsTM (CE) pig valve catheterization with RVOT reconstruction in the treatment of congenital heart disease in children and adults at the University of Rochester and the State University of New York North Medical Center from 2001 to 2009. A total of 208 patients underwent a single CE catheter RVOT reconstruction with a catheter size of 12-30mm. The perioperative mortality rate was 1.8% (4/208), and 95% of the remaining patients were observed continuously for 1-9 years. They found that the attenuation of the catheter worsened over time, contrary to the catheter specifications. For all specifications of catheters, 70.3% of patients do not require further surgery within 8.2 years, while patients using catheters with specifications of 25-30mm have not experienced catheter attenuation. Therefore, they believe that in mid-term observations, CE catheters exhibit an extended lifespan and slow catheter narrowing.

　　Konertz et al. analyzed the mid-term research results of three research institutions. From January 2006 to September 2008, a total of 61 patients were implanted with pig valve tissue engineering catheters of different sizes (valve sizes 11-27mm). The early mortality rate was 8.2%, all of which were due to non valve related reasons. Four patients underwent reoperation due to valve failure, three patients underwent RVOT intervention due to distal anastomotic stenosis, and six patients underwent reoperation due to underdeveloped pulmonary artery branches. CT and MRI examinations indicate that the tissue-engineered valve has normal structural features and no obvious calcification. Their conclusion is that the Matrix P/Matrix Plus catheter is feasible for RVOT reconstruction in patients with congenital heart disease, and the mid-term performance of tissue engineering catheters is significantly better than other current artificial valves.