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Rotator cuff supraspinatus tendon injuries are common with high rates of anatomic failure after surgical repair. The purpose of the study was to define clinically relevant features of a mouse model of supraspinatus tendon injury to determine painful, functional, and structural outcomes; we further investigated two cell populations mediating healing using genetic lineage tracing after full detachment and repair of the supraspinatus tendon in mice. The pain was assessed using the mouse grimace scale and function by gait analysis and tensile testing. Histological and microCT analyses were used to determine enthesis/tendon and bone structure, respectively. Lineage tracing was carried out using inducible Cre lines for ScxCreERT2 (tendon cells) and αSMACreERT2 (myofibroblasts and mesenchymal progenitors). Mice only expressed pain transiently after surgery despite long-term impairment of functional and structural properties. Gait, tensile mechanical properties, and bone properties were significantly reduced after injury and repair. Lineage tracing showed relatively few Scx lin tendon cells while αSMA lin cells contributed strongly to scar formation. Despite surgical reattachment of healthy tendon, lineage tracing revealed poor preservation of supraspinatus tendon after acute injury and loss of tendon structure, suggesting that tendon degeneration is also a key impediment of successful rotator cuff repair. Scar formation after surgery is mediated largely by αSMA lin cells and results in permanently reduced functional and structural properties., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Rotator cuff disease pathogenesis is associated with intrinsic (e.g., age, joint laxity, muscle weakness) and extrinsic (e.g., mechanical load, fatigue) factors that lead to chronic degeneration of the cuff tissues. However, etiological studies are difficult to perform in patients due to the long duration of disease onset and progression. Therefore, the purpose of this study was to determine the effects of altered joint loading on the rotator cuff. Mice were subjected to one of three load‐dependent rotator cuff tendinopathy models: underuse loading, achieved by injecting botulinum toxin‐A into the supraspinatus muscle; overuse loading, achieved using downhill treadmill running; destabilization loading, achieved by surgical excision of the infraspinatus tendon. All models were compared to cage activity animals. Whole joint function was assessed longitudinally using gait analysis. Tissue‐scale structure and function were determined using microCT, tensile testing, and histology. The molecular response of the supraspinatus tendon and enthesis was determined by measuring the expression of 84 wound healing‐associated genes. Underuse and destabilization altered forepaw weight‐bearing, decreased tendon‐to‐bone attachment strength, decreased mineral density of the humeral epiphysis, and reduced tendon strength. Transcriptional activity of the underuse group returned to baseline levels by 4 weeks, while destabilization had significant upregulation of inflammation, growth factors, and extracellular matrix remodeling genes. Surprisingly, overuse activity caused changes in walking patterns, increased tendon stiffness, and primarily suppressed expression of wound healing‐related genes. In summary, the tendinopathy models demonstrated how divergent muscle loading can result in clinically relevant alterations in rotator cuff structure, function, and gene expression. [ABSTRACT FROM AUTHOR]

The article presents a study that explores the mechanisms for the attachment of architectured materials and mechanics of the tendon enthesis. It mentions about the 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.