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Abstract: exosomes derived from bone marrow mesenchymal stem cells (BMSCs) show promising potential in the treatment of bone defects. However, their clinical application has been hindered by low yield and insufficient repair ability. Mechanical stimulation in 3D has been a well-known method to enhance exosome secretion, however, the traditional stimulation process was always achieved by controlling the displacement of manipulator, which may induce uneven loading distribution and degradation of stimulation strength. Here, we proposed a micro-stretching manipulator with a capacity of automatically controlling the stretching force applied to GelMA/HAMA hybrid hydrogel sheets containing BMSCs within an incubator. To ensure structural stability of the sheets after long-term stretching, the mixing ratio of GelMA and HAMA was optimized according to the mechanical property response of the sheets to cyclical loading. Subsequently, a force-controlled mechanical loading was applied to the BMSC-laden sheets in order to produce exosomes. Compare with the control for displacement, force-controlled loading has been demonstrated to provide a more stable force stimulation, thereby enhancing the secretion of exosomes. Furthermore, continuously stimulated exosomes have exhibited a more potent capacity in promoting the osteogenic differentiation of BMSCs and facilitating the repair of bone defects in a rat model. These findings suggest that force-controlled loading for cell-laden hydrogel offers a novel approach for the production of BMSC-exos and their application in bone repair