Mechanical stretch is widely experienced by cells of different tissues in the human body and plays critical roles in regulating their behaviors. Numerous studies have been devoted to investigating the responses of cells to mechanical stretch, providing us with fruitful findings. However, these findings have been mostly observed from two-dimensional studies and increasing evidence suggests that cells in three dimensions may behave more closely to their in vivo behaviors.

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While significant efforts and progresses have been made in the engineering of biomaterials and approaches for mechanical stretching of cells in three dimensions, much work remains to be done. Here, we briefly review the state-of-the-art researches in this area, with focus on discussing biomaterial considerations and stretching approaches. We envision that with the development of advanced biomaterials, actuators and microengineering technologies, more versatile and predictive three-dimensional cell stretching models would be available soon for extensive applications in such fields as mechanobiology, tissue engineering, and drug screening.

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