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Genetically engineered chondrocytes overexpressing elastin improve cell retention and chondrogenesis in a three-dimensional GelMA culture system
Authors:Wei Zhang  Wei Lu  Kexin Sun  Haiyue Jiang
Institution:Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
Abstract:Elastic cartilage possesses many elastic fibers and has a high degree of elasticity. However, insufficient elastic fiber production remains unsolved in elastic cartilage tissue engineering. Exogenous elastin is difficult to degrade and violates cell proliferation and migration during cartilage regeneration. Moreover, exogenous elastic fibers are difficult to assemble with endogenous extracellular matrix components. We produced genetically engineered chondrocytes overexpressing elastin to boost endogenous elastic fiber production. After identifying that genetic manipulation hardly impacted the cell viability and chondrogenesis of chondrocytes, we co-cultured genetically engineered chondrocytes with untreated chondrocytes in a three-dimensional gelatin methacryloyl (GelMA) system. In vitro study showed that the co-culture system produced more elastic fibers and increased cell retention, resulting in strengthened mechanics than the control system with untreated chondrocytes. Moreover, in vivo implantation revealed that the co-culture GelMA system greatly resisted host tissue invasion by promoting elastic fiber production and cartilage tissue regeneration compared with the control system. In summary, our study indicated that genetically engineered chondrocytes overexpressing elastin are efficient and safe for promoting elastic fiber production and cartilage regeneration in elastic cartilage tissue engineering.
Keywords:chondrocyte  elastic fiber  genetically engineered  tissue engineering
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