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

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. 1 Incidence of Soft-Tissue Injury in Sport Soft-tissue injuries, those affecting muscles, tendons, and ligaments, are extremely common at all levels of sport. In youth sport,*50% of all injuries are sprains [1]. In college athletics, the rates of ankle sprains remained relatively constant, at *1 per 1000 athlete exposures, over the 15 years between 1988 and 2004 [2]. By contrast, anterior cruciate ligament (ACL) ruptures increased by 1.3% per year to 0.14 per 1000 athlete exposures over the same time period. In professional sports, the incidence of soft-tissue injury for players reaches 60% for the English Premier League [3] and nearly 70% in the National Football League [4]. Beyond sporting populations, diabetic individuals are up to ten times more likely to experience tendon injuries than non-diabetic individuals [5], and tendon injuries increase with aging as evidenced by the fact that 80% of people in their 80 s have experienced a ruptured tendon [6]. Even though musculoskeletal injuries are extremely common and have huge personal, competitive, and financial costs, very few advances have been made in preventing these injuries. Tendons and ligaments are often grouped together into a single category (termed sinew in this review) because of similarities in their molecular composition, structure, and general function. However, the importance of the fundamental difference, that a tendon attaches a compliant tissue to a stiff tissue, whereas a ligament attaches two stiff tissues, is often underappreciated. The connection of two mechanically disparate tissues could result in stress and strain concentrations (i.e., one tissue stretches much more than another at the interface), which would lead to failure (rupture). The tendon overcomes this issue by being a variable mechanical tissue (Fig. 1) [7]. This means that a healthy tendon is more compliant near the muscle and & Keith Baar kbaar@ucdavis.edu 1 Department of Neurobiology, Physiology and Behavior, University of California Davis, One Shields Ave, Davis, CA 95616, USA 2 Department of Physiology and Membrane Biology, University of California Davis, One Shields Ave, Davis, CA 95616, USA 123 Sports Med (2017) 47 (Suppl 1):S5–S11 DOI 10.1007/s40279-017-0719-x