title: Improvement of In Vitro Three-Dimensional Cartilage Regeneration by a Novel Hydrostatic Pressure Bioreactor.
abstract: In vitro three-dimensional (3D) cartilage regeneration is a promising strategy for repair of cartilage defects. However, inferior mechanical strength and tissue homogeneity greatly restricted its clinical translation. Simulation of mechanical stress through a bioreactor is an important approach for improving in vitro cartilage regeneration. The current study developed a hydrostatic pressure (HP) bioreactor based on a novel pressure-transmitting mode achieved by slight deformation of a flexible membrane in a completely sealed stainless steel device. The newly developed bioreactor efficiently avoided the potential risks of previously reported pressure-transmitting modes and simultaneously addressed a series of important issues, such as pressure scopes, culture chamber sizes, sealability, contamination control, and CO2balance. The whole bioreactor system realized stable long-term (8 weeks) culture under high HP (5-10 MPa) without the problems of medium leakage and contamination. Furthermore, the results of in vitro 3D tissue culture based on a cartilage regeneration model revealed that HP provided by the newly developed bioreactor efficiently promoted in vitro 3D cartilage formation by improving its mechanical strength, thickness, and homogeneity. Detailed analysis in cell proliferation, cartilage matrix production, and cross-linking level of collagen macromolecules, as well as density and alignment of collagen fibers, further revealed the possible mechanisms that HP regulated in vitro cartilage regeneration. The current study provided a highly efficient and stable bioreactor system for improving in vitro 3D cartilage regeneration and thus will help to accelerate its clinical translation. Stem Cells Translational Medicine 2017;6:982-991.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.|Department of Anesthesiology, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Research Institute of Plastic Surgery, Wei Fang Medical College, Wei Fang, Shandong, People's Republic of China.
authors.forename: Zhaoyuan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.affiliation: College of Materials Science and Engineering, Hunan University, Changsha, Hunan, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.|Research Institute of Plastic Surgery, Wei Fang Medical College, Wei Fang, Shandong, People's Republic of China.
authors.forename: Huitang
authors.initials: H
authors.lastname: Xia
authors.affiliation: College of Materials Science and Engineering, Hunan University, Changsha, Hunan, People's Republic of China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|National Tissue Engineering Center of China, Shanghai, People's Republic of China.|Research Institute of Plastic Surgery, Wei Fang Medical College, Wei Fang, Shandong, People's Republic of China.
authors.forename: Guangdong
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019149:Bioreactors; D002358:Cartilage, Articular / Q000502:physiology* / Q000648:ultrastructure; D020219:Chondrogenesis; D003432:Cross-Linking Reagents / Q000378:metabolism; D055119:Elastic Modulus; D005109:Extracellular Matrix / Q000378:metabolism; D006874:Hydrostatic Pressure; D008954:Models, Biological; D012038:Regeneration; D013552:Swine; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*
chemical_list: D003432:Cross-Linking Reagents
keywords: Bioreactor; Hydrostatic pressure; In vitro; Three-dimensional cartilage regeneration; Tissue engineering