Study on Decellularized Porcine Aortic Valve/Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) Hybrid Heart Valve in Sheep Model *Song Wu, *Ying-Long Liu, *Bin Cui, †Xiang-Hua Qu, and †Guo-Qiang Chen *Department of Cardiovascular Surgery, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College; and †Department of Biological Science and Biotechnology,Tsinghua University, Beijing, China Abstract: To overcome shortcomings of current heart valve prostheses, novel hybrid valves were fabricated from decellularized porcine aortic valves coated with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate [PHBHHx]). In the mechanical test in vitro, the biomechanical perfor- mance of hybrid valve was investigated. In an in vivo study, hybrid valve conduits were implanted in pulmonary posi- tion in sheep without cardiopulmonary bypass. Uncoated grafts were used as control. The valves were explanted and examined histologically and biochemically 16 weeks after surgery. The hybrid valve conduits maintained original shapes, were covered by a confluent layer of cells, and had less calcification than uncoated control. The mechanical test in vitro revealed that PHBHHx coating improved tensile strength.The results in vivo indicated that PHBHHx coating reduced calcification and promoted the repopula- tion of hybrid valve with the recipient’s cells resembling native valve tissue. The hybrid valve may provide superior valve replacement with current techniques. Key Words: Decellularized porcine aortic valves—Poly (3-hydroxy butyrate-co-3-hydroxyhexanoate)—Hybrid tissue heart valves—Cardiovascular tissue engineering—Extracellular matrix—Biocompatibility. Currently, valve substitutes used for valve replace- ment have certain disadvantages that limit their long- term benefits such as poor durability,risks of infection, thromboembolism, or rejection. Tissue-engineered heart valves (TEHVs) may have the potential to over- come these shortcomings. Recently, a novel TEHV based on a decellularized xenogenic valve that has been coated with biodegradable poly (3- hydroxybutyrate-co-4-hydroxybutyrate) (P [3HB-co- 4HB]) has been developed and examined in vivo. Early results are promising (1). However, the brittle- ness and low mechanical strength of poly (3-hydroxybutyrate) (P3HB) have significantly limited its application. P3HB has also been reported to induce prolonged acute and chronic inflammatory responses (2). Poly (3-hydroxybutyrate-co-3-hydroxyhexanoate [PHBHHx]), which is a new biodegradable polymer and a member of polyhydroxyalkanoates (PHAs), may be more practical for tissue engineering applica- tions. Its mechanical and process properties have been shown to be better than P3HB and poly (3- hydroxybutyrate-co-3-hydroxyvalerate) (3). In vitro tests have shown that PHBHHx is biocompatible to several cells (4,5). Considering its desirable strength and elastic properties which are adjustable by chang- ing its monomer contents, PHBHHx can be tailored to meet the requirement of cardiovascular tissue engi- neering (6). The aim of this study was to use decellu- larized porcine aortic valves coated with PHBHHx to develop hybrid valves that were implanted in pulmo- nary position in sheep models. MATERIALS AND METHODS Decellularization procedure Porcine hearts (weight: 50–60 kg) were obtained from Shunyi slaughterhouse, Beijing, China. Porcine doi:10.1111/j.1525-1594.2007.00442.x Received August 2006; revised January 2007. Address correspondence and reprint requests to Dr. Song Wu, Department of Cardiovascular Surgery, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China. E-mail: drwusong@gmail.com Artificial Organs 31(9):689–697, Blackwell Publishing, Inc. © 2007, Copyright the Authors Journal compilation © 2007, International Center for Artificial Organs and Transplantation and Blackwell Publishing 689