Growth factor delivery using polymer matrices is one exciting approach to replace or regenerate tissues. Most growth factor delivery systems, however, have been designed to operate under static conditions, regardless of dynamic environments in the body. Considering the dynamic environment of our body (e.g., bone, muscle, and blood vessel), mechanical stimulation is an important signal that could be readily exploited. We hypothesize that polymer matrices, which release growth factors in response to mechanical stimulation, could provide a novel approach to engineer tissues in mechanically stressed environments. We report here a model system, comprised of alginate hydrogel and vascular endothelial growth factor (VEGF), which upregulates the release of the growth factor in response to mechanical stimulation and subsequently promotes granulation tissue formation in animals. This approach may find a number of potential applications in tissue engineering, as well as in drug delivery.