Minimizing Injury and Maximizing Return to Play: Lessons from Engineered Ligaments

Musculoskeletal injuries account for more than 70% of time away from sports. One of the reasons for the high number of injuries and long return to play is that we have only a very basic understanding of how our training alters tendon and ligament (sinew) structure and function. Sinews are highly dense tissues that are difficult to characterize both in vivo and in vitro. Recently, engineered ligaments have been developed in vitro using cells from human anterior cruciate ligaments or hamstring tendons. These three-dimensional tissues can be grown in a laboratory, treated with agents thought to affect sinew physiology, and then mechanically tested to determine their function. Using these tissues, we have learned that sinews, like bone, quickly become refractory to an exercise stimulus, suggesting that short (<10 min) periods of activity with relatively long (6 h) periods of rest are best to train these tissues. The engineered sinews have also shown how estrogen decreases sinew function and that a factor released following intense exercise increases sinew collagen synthesis and function. Last, engineered sinews are being used to screen possible nutritional interventions that may benefit tendon or ligament function. Using the data derived from these tissue-engineered sinews, new nutritional and training regimes are being designed and tested with the goal of minimizing injury and accelerating return to play.