Mechanical loading plays an important role in the initiation and progression of orthopedic diseases such as osteoarthritis. Despite their growing economic burden and negative impact on patients’ quality of life, effective methods of predicting, delaying, preventing or reversing most orthopedic diseases have not been established. While joint-scale mechanical causes of disease are largely understood, tissue-level stress and strain thresholds that cause tissue damage are lacking. Knowledge of the effects of tissue-level mechanics would provide the basis for predicting when and where tissue damage will occur under arbitrary loading conditions, ultimately improving our understanding of orthopedic diseases and improving the efficacy of treatment. Establishing tissue-level mechanics that cause failure in orthopedic tissues has remained elusive due to the short time- and length-scales of interest. Thus, the central hypothesis of the Henak Lab is that the tissue-scale mechanical environment can be used to understand and predict orthopedic diseases. To address this hypothesis, the Henak Lab uses a combination of multiscale experimental and computational techniques.