Although perhaps less so than bone and muscle, extensive research on the adaptation of tendons to mechanical stresses has been conducted (Killian et al., 2012b; Wang, 2006). Most investigations have focused on the tendon proper, finding that the nature of loading directs the homeostatic balance between anabolic and catabolic pathways in resident fibroblasts (Killian et al., 2012a). The role of mechanical stimulation in tendon healing is discussed below. In addition, researchers have recently explored the role of mechanical loading on the bone-tendon insertion site (Benjamin et al., 2006). Using a mouse model, Thomopoulos et al. showed that decreased muscle loading delayed maturation of the supraspinatus enthesis during postnatal development. While a fibrocartilage transition was identified in both experimental and control animals at 14 days post-birth, the mice with reduced muscle loading demonstrated less mineral deposition, impaired fibrochondrocyte and matrix organization, and inferior mechanical properties at later time points (Thomopoulos et al., 2010). This study, among others, reinforces the importance of proper mechanical loading in maintaining the health of the mature musculoskeletal system, but also in driving the appropriate maturation of these developing structures early in life. Should tendon injury occur, the implementation of physical rehabilitation protocols is equally important in regaining tendon function, though the innate healing process of tendons is quite poor, as highlighted below.
TENDON INJURY AND NATURAL HEALING
Tendon injuries, broadly categorized as chronic degenerative tendinopathies or acute ruptures, are a common clinical problem. Degenerative tendinopathy often precedes acute ruptures, with the former considered a failed healing response that is characterized by hypervascularity, mucoid degeneration, ectopic bone and cartilage nodules, and disorganized extracellular matrix (Kannus and Jozsa, 1991; Riley, 2008). Given the temporal relationship between chronic and acute tendon injuries, it is arguable that research examining the interaction between both pathologies will provide insights into the common clinical scenario. However, most in vivo studies of the sequelae of acute tendon ruptures are performed in animal models with previously healthy tendons. Therefore the applicability of research findings to the human condition may be questioned. Nevertheless, the current understanding of the innate healing response following acute tendon injury follows.
An estimated 300,000 tendon and ligament repair surgeries are performed annually in the U.S (Pennisi, 2002). In spite of surgical intervention, the natural healing process of tendons is still slow, due to their hypocellular and hypovascular nature (Liu et al., 2011). Even after one year, the structure and function of the resulting tissue remain inferior to uninjured tendons. The healing response is predicable, and is traditionally divided into three overlapping stages – (1) inflammation, (2) proliferation/repair, and (3) remodeling (Hope and Saxby, 2007). In the inflammatory stage, the blood clot that forms immediately following rupture of tendon vessels activates the release of chemoattractants and serves as a preliminary scaffold for invading cells. Inflammatory cells including neutrophils, monocytes, and lymphocytes migrate from surrounding tissues into the wound site, where necrotic debris is digested by phagocytosis (Voleti et al., 2012). Additionally, the recruitment and activation of tenocytes begins, but peaks in the subsequent stage. The second stage, known as the proliferative or reparative phase, begins roughly two days after