Growth factors play an important role in supraspinatus tendon-to-bone healing. The objective of this study was to evaluate the temporal expression of 8 different growth factors in tendon-to-bone healing in an animal model. We hypothesize that growth factors exhibit unique temporal profiles that correlate to specific stages in the acute process of the supraspinatus tendon. To test this hypothesis, rats underwent bilateral supraspinatus tendon detachment and repair. Animals were euthanized at 1, 2, 4, 8, and 16 weeks. Immunohistochemical staining was done using antibodies for basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12), BMP-13, BMP-14, cartilage oligomeric matrix protein (COMP), connective tissue growth factor (CTGF), platelet-derived growth factor-B (PDGF-B), and transforming growth factor-beta1 (TGF-beta1). Immunoassays showed an increase in the expression of all growth factors at 1 week, followed by a return to control or undetectable levels by 16 weeks in both the insertion and midsubstance. Future studies will investigate the different impacts of growth factor expression in tendon to bone healing.

The interactions of small leucine-rich proteoglycans (SLRPs) with collagen fibrils, their association with water, and their role in fibrillogenesis suggests that SLRPs may play an important role in tendon mechanics. Some studies have assessed the role of SLRPs in the mechanical response of the tendon, but the relationships between sophisticated mechanics, assembly of collagen, and SLRPs have not been well characterized. Decorin content was varied in a dose dependent manner using decorin null, decorin heterozygote, and wild type mice. Quantitative measures of mechanical (tension and compression), compositional, and structural changes of the mouse patellar tendon were evaluated. Viscoelastic, tensile dynamic modulus was increased in the decorin heterozygous tendons compared to wild type. These tendons also had a significant decrease in total collagen and no structural changes compared to wild type. Decorin null tendons did not have any mechanical changes; however, a significant decrease in the average fibril diameter was found. No differences were seen between genotypes in elastic or compressive properties, and all tendons demonstrated viscoelastic mechanical dependence on strain rate and frequency. These results suggest that decorin, a member of the SLRP family, plays a role in tendon viscoelasticity that cannot be completely explained by its role in collagen fibrillogenesis. In addition, reductions in decorin do not cause large changes in indentation compressive properties, suggesting that other factors contribute to these properties. Understanding these relationships may ultimately help guide development of tissue engineered constructs or treatment modalities.

In this model, immediate postoperative passive motion was found to be detrimental to passive shoulder mechanics. We speculate that passive motion results in increased scar formation in the subacromial space, thereby resulting in decreased range of motion and increased joint stiffness. Passive motion had no effect on collagen organization or tendon mechanical properties measured six weeks after surgery.

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Tendons have complex mechanical properties that depend on their structure and composition. Some studies have assessed the role of small leucine-rich proteoglycans (SLRPs) in the mechanical response of tendon, but the relationships between sophisticated mechanics, assembly of collagen and SLRPs have not been well characterized. In this study, biglycan gene expression was varied in a dose dependent manner using biglycan null, biglycan heterozygote and wild type mice. Measures of mechanical (tension and compression), compositional and structural changes of the mouse patellar tendon were evaluated. Viscoelastic, tensile dynamic modulus was found to be increased in the biglycan heterozygous and biglycan null tendons compared to wild type. Gene expression analyses revealed biglycan gene expression was closely associated in a dose-dependent allelic manner. No differences were seen between genotypes in elastic or compressive properties or quantitative measures of collagen structure. These results suggest that biglycan, a member of the SLRP family, plays a role in tendon viscoelasticity that cannot be completely explained by its role in collagen fibrillogenesis.

While rotator cuff repair is often successful at relieving pain, the repaired insertion site can fail. The repaired mechanical properties improved when the shoulder was immobilized in an animal model, but joint stiffness and range of motion were not evaluated. This study objective was to measure rotational mechanics before and after shoulders were immobilized following cuff injury/ repair, not immobilized following cuff injury/repair, and immobilized without injury/repair. Humeral rotation was significantly less 4 and 8 weeks following injury/repair but did not decrease significantly when the injured/repaired shoulder was immobilized. Rotational stiffness increased significantly 4 and 8 weeks following injury/repair and was significantly greater at 4, but not 8, weeks when the injured/repaired shoulders were immobilized. This study demonstrates that the increase in joint stiffness caused by immobilizing an injured/repaired shoulder is transient and, therefore, does not outweigh the long-term benefits of immobilization on improved tendon to bone healing.

Rotator cuff tears are a common clinical problem that can result in pain and disability. Previous studies in a rat model showed enhanced tendon to bone healing with postoperative immobilization. The objective of this study was to determine the effect of postimmobilization activity level on insertion site properties and joint mechanics in a rat model. Our hypothesis was that exercise following a short period of immobilization will cause detrimental changes in insertion site properties compared to cage activity following the same period of immobilization, but that passive shoulder mechanics will not be affected. We detached and repaired the supraspinatus tendon of 22 Sprague-Dawley rats, and the injured shoulder was immobilized postoperatively for 2 weeks. Following immobilization, rats were prescribed cage activity or exercise for 12 weeks. Passive shoulder mechanics were determined, and following euthansia, tendon cross-sectional area and mechanical properties were measured. Exercise following immobilization resulted in significant decreases compared to cage activity in range of motion, tendon stiffness, modulus, percent relaxation, and several parameters from both a structurally based elastic model and a quasilinear viscoelastic model. Therefore, we conclude that after a short period of immobilization, increased activity is detrimental to both tendon mechanical properties and shoulder joint mechanics, presumably due to increased scar production. ß

Background Chronic rotator cuff tears are often associated with pain or poor function. In a rat with only a detached supraspinatus tendon, the tendon heals spontaneously which is inconsistent with how tears are believed to heal in humans. Questions/purposes We therefore asked whether a combined supraspinatus and infraspinatus detachment in the rat would fail to heal and result in a chronic injury in the supraspinatus tendon. Methods We acutely detached the supraspinatus and infraspinatus tendons in a rat model. At 4, 8, and 16 weeks post-detachment, biomechanical testing, collagen organization, and histological grading were evaluated for the detached supraspinatus and infraspinatus tendons and compared to controls. Results In the detached supraspinatus tendon, area and percent relaxation were increased at all time points while the modulus and stiffness were similar to those of controls at 4 and 8 weeks. Collagen disorganization increased at late time points while cellularity increased and cells were more rounded in shape. In the detached infraspinatus tendon, area and percent relaxation were also increased at late time points. However, the modulus values initially decreased followed by an increase in both modulus and stiffness at 16 weeks compared to control. In the detached infraspinatus, we also observed a decrease in collagen organization at all time points and increased cellularity and a more rounded cell shape. Conclusions Due to the ongoing changes in mechanics, collagen organization and histology in the detached supraspinatus tendon compared to control animals at 16 weeks, this model may be useful for understanding the human chronic tendon tear. Clinical Relevance This rat rotator cuff chronic model can be used to test hypotheses regarding injury and repair mechanisms that cannot be addressed in human patients or in cadaveric studies.