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 CO2 balance. 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
Highlights
Functional repair of cartilage defects is a challenging task because of the avascular and limited self-repair nature of cartilage tissue [1, 2]
Whether hydrostatic pressure (HP) provided by the current bioreactor had significant effects on in vitro cartilage formation was an important issue in the current study
The current study developed an HP bioreactor based on a novel pressure-transmitting modes, which efficiently addressed the above issues in the same system and realized long-term culture under high HP without medium leakage and contamination
Summary
Functional repair of cartilage defects is a challenging task because of the avascular and limited self-repair nature of cartilage tissue [1, 2]. Along with technology development and ascending requirements of clinical translation, in vitro tissue regeneration gradually becomes an important research direction because of such advantages as low cell loss, low inflammatory reaction, ease of handling, standard manufacture, and controllable quality [5, 6]. As a result of its avascular nature, cartilage is one of the earliest tissues to have been successfully engineered in vitro. Tissue structure and function of the in vitro engineered cartilage (vitro-EC) are still inferior to those of the native cartilage [1]; this has become one of the main obstacles impeding clinical application
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