Mechanical, compositional, and structural properties of the mouse patellar tendon with changes in biglycan gene expression.

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.

Influence of decorin on the mechanical, compositional, and structural properties of the mouse patellar tendon.

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.

Fiber-aligned polymer scaffolds for rotator cuff repair in a rat model.

BACKGROUND: Repair techniques of rotator cuff tendon tears have improved in recent years; nonetheless, the failure rate remains high. Despite the availability of various graft materials for repair augmentation, there has yet to be a biomechanical study using fiber-aligned scaffolds in vivo. The objective of this study was to evaluate the efficacy of fiber-aligned nanofibrous polymer scaffolds as a potential treatment-delivery vehicle in a rat rotator cuff injury model. MATERIALS AND METHODS: Scaffolds with and without sacrificial fibers were fabricated via electrospinning and implanted to augment supraspinatus repair in rats. Repairs without scaffold augmentation were also performed to serve as controls. Rats were sacrificed at 4 and 8 weeks postoperatively, and repairs were evaluated histologically and biomechanically. RESULTS: Both scaffold formulations remained in place, with more noticeable cellular infiltration and colonization at 4 and 8 weeks after injury and repair for scaffolds lacking sacrificial fibers. Specimens with scaffolds were larger in cross-sectional area compared with controls. Biomechanical testing revealed no significant differences in structural properties between the groups. Some apparent material properties were significantly reduced in the scaffold groups. These reductions were due to increases in cross-sectional area, most likely caused by the extra thickness of the implanted scaffold material. No differences were observed between the 2 scaffold groups. CONCLUSIONS: No adverse effect of surgical implantation of overlaid fiber-aligned scaffolds on structural properties of supraspinatus tendons in rat rotator cuff repair was demonstrated, validating this model as a platform for targeted delivery.

Tendon properties remain altered in a chronic rat rotator cuff model.

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.

Exercise following a short immobilization period is detrimental to tendon properties and joint mechanics in a rat rotator cuff injury model.

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 euthanasia, 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 quasi-linear 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.

The effect of postoperative passive motion on rotator cuff healing in a rat model.

BACKGROUND: Surgical repairs of torn rotator cuff tendons frequently fail. Immobilization has been shown to improve tissue mechanical properties in an animal model of rotator cuff repair, and passive motion has been shown to improve joint mechanics in animal models of flexor tendon repair. Our objective was to determine if daily passive motion would improve joint mechanics in comparison with continuous immobilization in a rat rotator cuff repair model. We hypothesized that daily passive motion would result in improved passive shoulder joint mechanics in comparison with continuous immobilization initially and that there would be no differences in passive joint mechanics or insertion site mechanical properties after four weeks of remobilization. METHODS: A supraspinatus injury was created and was surgically repaired in sixty-five Sprague-Dawley rats. Rats were separated into three postoperative groups (continuous immobilization, passive motion protocol 1, and passive motion protocol 2) for two weeks before all underwent a remobilization protocol for four weeks. Serial measurements of passive shoulder mechanics (internal and external range of motion and joint stiffness) were made before surgery and at two and six weeks after surgery. After the animals were killed, collagen organization and mechanical properties of the tendon-to-bone insertion site were determined. RESULTS: Total range of motion for both passive motion groups (49% and 45% of the pre-injury values) was less than that for the continuous immobilization group (59% of the pre-injury value) at two weeks and remained significantly less following four weeks of remobilization exercise. Joint stiffness at two weeks was increased for both passive motion groups in comparison with the continuous immobilization group. At both two and six weeks after repair, internal range of motion was significantly decreased whereas external range of motion was not. There were no differences between the groups in terms of collagen organization or mechanical properties. CONCLUSIONS: 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.

Twenty-five years of tendon and ligament research.

Twenty-five years ago, the Journal of Orthopaedic Research published its first volume, which included five articles covering topics in tendon and ligament research. Since then, the body of tendon and ligament research has continued to increase exponentially. This review summarizes major advancements in tendon and ligament research since the initial publication of this journal. The purpose of this article is not to provide an in-depth review of all of tendon and ligament research, but instead to provide a concise literature review of some of the major and recurring areas of research. The general topics covered over the last 25 years include tissue properties, tendinopathy, healing, and engineered scaffolds.

Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model.

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.

Mechanical heart valve performance in a pulsatile pediatric ventricular assist device.

A pulsatile pediatric ventricular assist device with a dynamic stroke volume of 12 ml is currently under development at the Pennsylvania State University. A monoleaflet valve (Björk-Shiley Monostrut) and a bileaflet valve (CPHV, CarboMedics Prosthetic Heart Valve) were examined in this study. A high-speed video and data acquisition system was used to simultaneously record video images, pressure waveforms, and flow waveforms for an array of in vitro test conditions that varied heart rate and systolic duration. The CPHV in both the horizontal and vertical orientations have larger regurgitant volumes than the Monostrut valves at all operating conditions in both the inlet and outlet positions. However, the CPHV has higher stroke volumes and cardiac outputs than the Monostrut valve at higher heart rates and longer systolic durations. In addition, the hydrodynamic performance of the Monostrut valve is more sensitive to changes in operating conditions for the pulsatile pediatric ventricular assist device than the CPHV in both orientations. Additional testing is under way to identify the optimal operating conditions for each type of valve.