DescriptionTendons and ligaments (T/L) are collagenous connective tissues that play a role in locomotion and mechanical stabilization of the joints. These tissues possess relatively low cellularity and vascularity, resulting in a long and potentially incomplete healing response following injury. For sub-failure injuries such as strains and sprains, the most common course of treatment is an implementation of rest, ice, compression, and elevation. However, this method relies mostly on the tissue's natural ability to heal, which can leave the tissue prone to re-injury and failure. As a potential aid in the T/L healing process, we investigated the effects of thermal stress on human tenocytes in vitro. Heat shock has been demonstrated to improve regeneration in other tissues of the musculoskeletal system, including bone and muscle. Exposure of cells to an increase in temperature induces the production of heat shock proteins (HSPs) which act as molecular chaperones to assist in protein assembly and transport. In this project, heat shock at 40°, 44°, and 48°C was applied for 5, 10, 15, or 20 minutes. The data shows an increase in cellular proliferation following 15 and 20 minutes of thermal conditioning at 44° and 48°C as soon as 4 hours after heat shock. Protein secretion and gene expression of collagens type I and III and TGF-β suggest that that the heat shock response of tenocytes is similar to that of natural wound healing. Lastly, an in vitro scratch wound healing assay revealed that the use of heat may hasten the recovery time following T/L subfailure injuries.