title: Initiation of Chondrocyte Self-Assembly Requires an Intact Cytoskeletal Network.
abstract: Self-assembly and self-organization have recently emerged as robust scaffold-free tissue engineering methodologies that can be used to generate various tissues, including cartilage, vessel, and liver. Self-assembly, in particular, is a scaffold-free platform for tissue engineering that does not require the input of exogenous energy to the system. Although self-assembly can generate functional tissues, most notably neocartilage, the mechanisms of self-assembly remain unclear. To study the self-assembling process, we used articular chondrocytes as a model to identify parameters that can affect this process. Specifically, the roles of cell-cell and cell-matrix adhesion molecules, surface-bound collagen, and the actin cytoskeletal network were investigated. Using time-lapse imaging, we analyzed the early stages of chondrocyte self-assembly. Within hours, chondrocytes rapidly coalesced into cell clusters before compacting to form tight cellular structures. Chondrocyte self-assembly was found to depend primarily on integrin function and secondarily on cadherin function. In addition, actin or myosin II inhibitors prevented chondrocyte self-assembly, suggesting that cell adhesion alone is not sufficient, but rather the active contractile actin cytoskeleton is essential for proper chondrocyte self-assembly and the formation of neocartilage. Better understanding of the self-assembly mechanisms allows for the rational modulation of this process toward generating neocartilages with improved properties. These findings are germane to understanding self-assembly, an emerging platform for tissue engineering of a plethora of tissues, especially as these neotissues are poised for translation.
authors.affiliation: 1 Department of Biomedical Engineering, University of California , Davis, Davis, California.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Lee
authors.affiliation: 1 Department of Biomedical Engineering, University of California , Davis, Davis, California.
authors.forename: Jerry C Y
authors.initials: JC
authors.lastname: Hu
authors.affiliation: 1 Department of Biomedical Engineering, University of California , Davis, Davis, California.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: 1 Department of Biomedical Engineering, University of California , Davis, Davis, California.|2 Department of Orthopedic Surgery, University of California , Davis, Davis, California.
authors.forename: Kyriacos A
authors.initials: KA
authors.lastname: Athanasiou
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D008954:Models, Biological