Tension is a principal force experienced by skin and serves a critical role in growth and development. Optimal tension application regimens may be an important component for skin tissue engineering and dermatogenesis. In this study, we designed and tested a novel servo-controlled skin-stretching device to apply predetermined tension and waveforms in mice. The effects of static and cyclical stretching forces were compared in 48 mice by measuring epidermal proliferation, angiogenesis, cutaneous perfusion, and principal growth factors using immunohistochemistry, real-time reverse transcriptase-polymerase chain reaction, and hyperspectral imaging. All stretched samples had upregulated epidermal proliferation and angiogenesis. Real-time reverse transcriptase-polymerase chain reaction of epidermal growth factor, transforming growth factor beta1, and nerve growth factor demonstrated greater expression in cyclically stretched skin when compared to static stretch. Hypoxia-induced factor 1alpha was significantly upregulated in cyclically stretched skin, but poststretch analysis demonstrated well-oxygenated tissue, collectively suggesting the presence of transient hypoxia. Waveform-specific mechanical loads may accelerate tissue growth by mechanotransduction and as a result of repeated cycles of temporary hypoxia. Further analysis of mechanotransduction signaling pathways may provide additional insight to improve skin tissue engineering methods and optimize our device.