Tendon disorders represent the most common musculoskeletal complaint for which patients seek medical attention; inflammation drives tendon degeneration before tearing and impairs healing after repair. Clinical evidence has implicated the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway as a correlate of pain-free return to function after surgical repair. However, it is currently unknown whether this response is a reaction to or a driver of pathology. Therefore, we aimed to understand the clinically relevant involvement of the NF-κB pathway in tendinopathy, to determine its potential causative roles in tendon degeneration, and to test its potential as a therapeutic candidate. Transcriptional profiling of early rotator cuff tendinopathy identified increases in NF-κB signaling, including increased expression of the regulatory serine kinase subunit IKKβ, which plays an essential role in inflammation. Using cre-mediated overexpression of IKKβ in tendon fibroblasts, we observed degeneration of mouse rotator cuff tendons and the adjacent humeral head. These changes were associated with increases in proinflammatory cytokines and innate immune cells within the joint. Conversely, genetic deletion of IKKβ in tendon fibroblasts partially protected mice from chronic overuse–induced tendinopathy. Furthermore, conditional knockout of IKKβ improved outcomes after surgical repair, whereas overexpression impaired tendon healing. Accordingly, targeting of the IKKβ/NF-κB pathway in tendon stromal cells may offer previously unidentified therapeutic approaches in the management of human tendon disorders.
Background: Patellar tendinopathy is an overuse injury of the patellar tendon frequently affecting athletes involved in jumping sports. The tendinopathy may progress to partial patellar tendon tears (PPTTs). Current classifications of patellar tendinopathy are based on symptoms and do not provide satisfactory evidence-based treatment guidelines. Purpose: To define the relationship between PPTT characteristics and treatment guidelines, as well as to develop a magnetic resonance imaging (MRI)–based classification system for partial patellar tendon injuries. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: MRI characteristics and clinical treatment outcomes were retrospectively reviewed for 85 patients with patellar tendinopathy, as well as 86 physically active control participants who underwent MRI of the knee for other conditions. A total of 56 patients had a PPTT and underwent further evaluation for tear size and location. The relationship between tear characteristics and clinical outcome was defined with use of statistical comparisons and univariate and logistic regression models. Results: Of the 85 patients, 56 had partial-thickness patellar tendon tears. Of these tears, 91% involved the posterior and posteromedial regions of the proximal tendon. On axial MRI views, patients with a partial tear had a mean tendon thickness of 10 mm, as compared with 6.2 mm for those without ( P < .001). Eleven patients underwent surgery for their partial-thickness tear. All of these patients had a tear >50% of tendon thickness (median thickness of tear, 10.3 mm) on axial views. Logistic regression showed that tendon thickness >8.8 mm correlated with the presence of a partial tear, while tendon thickness >11.45 mm and tear thickness >55.7% predicted surgical management. Conclusion: Partial-thickness tears are located posterior or posteromedially in the proximal patellar tendon. The most sensitive predictor for detecting the presence of a partial tear was patellar tendon thickness, in which thickness >8.8 mm was strongly correlated with a tear of the tendon. Tracking thickness changes on axial MRI may predict the effectiveness of nonoperative therapy: athletes with patellar tendon thickness >11.5 mm and/or >50% tear thickness on axial MRI were less likely to improve with nonoperative treatment. A novel proposed classification system for partial tears, the Popkin-Golman classification, can be used to guide treatment decisions for these patients.
Current surgical techniques for tendon-to-bone repair have unacceptably high failure rates, indicating that the initial repair strength is insufficient to prevent gapping or rupture. In the rotator cuff, repair techniques apply compression over the repair interface to achieve contact healing between tendon and bone, but transfer almost all force in shear across only a few points where sutures puncture the tendon. Therefore, we evaluated the ability of an adhesive film, implanted between tendon and bone, to enhance repair strength and minimize the likelihood of rupture. Mechanical models demonstrated that optimally designed adhesives would improve repair strength by over 10-fold. Experiments using idealized and clinically-relevant repairs validated these models. This work demonstrates an opportunity to dramatically improve tendon-to-bone repair strength using adhesive films with appropriate material properties.
Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and previously unexplored imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.
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