Biology Votes Repair?

Every patient who arrives in the office with an acute Achilles tendon rupture receives similar advice—we have compelling evidence that both operative and nonoperative management provide satisfactory results. Inevitably, many patients are skeptical. If the results are similar, why does every professional athlete undergo Achilles repair? In our practice, I usually discussed the improved mechanical strength achieved with repair and concerns about elongation and rerupture in high-level athletes, while acknowledging that surgery carries risks. Achilles tendon rupture management likely represents a case of clinical equipoise. And yet, as a surgeon, I have always believed (or desired to believe) that surgery must be better. The article by Wei et al. lends support to the notion that repair is biologically superior to nonoperative management. The authors studied mice, comparing surgical repair versus nonoperative management after tenotomy. Their study was large, with nearly 200 mice, and the authors should be congratulated on their use of an external fixator to ensure that post-injury positioning was standardized. The authors had 5 groups of mice: (1) control, (2) injury+no repair+90° immobilization, (3) injury+no repair+160° immobilization, (4) injury+repair+90° immobilization, and (5) injury+repair+160° immobilization. The authors provided proof of concept that immobilization in plantar flexion is of paramount importance. The tendons repaired and then immobilized at 90° had less biomechanical strength than the tendons immobilized at 160°, regardless of whether the tendon was repaired. Supporting the healing tendon in plantar flexion also led to better qualitative histological grading scores. Surgically repairing the tendon combined with plantar-flexed immobilization increased tendon-related gene expression, while not repairing the injury led to a stronger inflammatory response. In their discussion, the authors emphasized the importance of a low-tension environment for collagen remodeling and tissue quality. One clinical challenge is how to advise patients who have been immobilized in neutral dorsiflexion rather than plantar flexion prior to presentation. If the patient has been immobilized in neutral for more than a few days, are the results of nonoperative management still noninferior to those of surgery? While more study is needed to answer that and other questions, this study highlights the importance of plantar flexion for creating a low-tension environment to optimize tendon healing. The study has many unavoidable limitations that hinder generalizability to our patients. The Achilles tendon in mice is quite different from the Achilles tendon in humans. Mice are quadrupeds and, as such, the importance of the Achilles tendon for locomotion is lessened; mice walk well with the loss of a leg, but humans do not. Additionally, many Achilles tendon ruptures are related to underlying tendinopathy, while this model created ruptures by a tenotomy. In a spontaneous rupture, the ends of an Achilles tendon look like a horse’s tail, not a transverse cut. It is possible that spontaneous ruptures lend themselves to healing due to overlapping tissue and increased surface area. On the other hand, it is also possible that spontaneous ruptures increase collagen disorganization and therefore healing is of lower quality in humans. Finally, it is difficult to know if the results of this study will hold up in the long term, given the relatively short follow-up timeline. This study tested 2 immobilization paradigms—constant plantar flexion and constant neutral immobilization—that do not fully reflect the standard clinical protocol. Prolonged immobilization in plantar flexion has fallen out of favor clinically and has been replaced with progressive loading that aims to safely introduce the mechanical loading needed to promote tendon remodeling and more organized type-I collagen. The findings in this mouse experiment suggest that continued underloading in plantar flexion is optimal for tendon healing, but our clinical experience and other preclinical experiments suggest otherwise. A 2019 study by Hillin et al. tested the isolated effects of immobilization paradigms following an unrepaired Achilles tendon transection in a rat model1. They found that prolonged plantar flexion immobilization reduced tendon elongation but at the cost of reduced collagen organization, while prolonged neutral immobilization improved collagen organization but with increased elongation. Progressively reducing plantar flexion immobilization in that model improved tendon properties while minimizing elongation. Clinicians should carefully consider the implications of immobilization strategies and practical considerations when considering preclinical reports. Despite the limitations of animal research, however, this paper presents novel findings that are important to our understanding of optimizing tendon healing.