Significance of granulation tissue in torn supraspinatus insertions: An immunohistochemical study with antibodies against interleukin-1β, cathepsin D,and matrix metalloprotease-1

The pathophysiology of rotator cuff tears can be elucidated by examining the tendinous insertion of the supraspinatus musele. As seen by light microscopy, the granulation tissue around the insertion of a torn supraspinatus tendon appears to induce osteochondral destruction by means of multinucleated giant cells and chemical mediators. The purpose of this study was to examine the contribution of certain chemical mediators to osteochondral destruction using immunohistochemical analysis of interleukin-β, cathepsin D, and matrix metalloprotease-1. Sixteen supraspinatus insertions with portions of the greater tuberosity, including eight complete-thickness tears and eight incomplete-thickness tears, were obtained during surgery. Six fresh cadaveric supraspinatus tendons without grossly evident tears served as normal controls. Strong immunoreactivity was found in all 16 torn supraspinatus insertions but not in the six insertions of apparently intact tendons. Macrophages and multinucleated giant cells, which showed immunoreactivity for all three chemical mediators, were often found at the interface between the osteochondral margin of the enthesis and the granulation tissue, suggesting that they may be involved in osteochondral destruction. We therefore concluded that, in addition to repetitive subacromial impingement, this granulation tissue may contribute to the development of rotator cuff tears by weakening the insertion.     

Pathological study of the supraspinatus tendon

To clarify the aging process and pathogenesis of rotator cuff tears, left supraspinatus tendons from 268 cadaveric specimens (171 men and 97 women, ages 0 to 87 years) were studied. The incidence of complete thickness tear was 6.7%, and that of incomplete thickness tear was 13.8% (bursal side tears: 2.6%, intratendinous tears: 7.5% and joint side tears: 3.7%). Microscopic examinations were conducted topographically in five sites near the supraspinatus insertion. In the articular side of the tendon, there were fewer tenocytes, fewer arterioles and more chondrocyte like cells than in any other portions. The incidence of hyperplasia of intima was higher in the specimens of aged persons in all portions. At the insertion in the aged specimens the arrangement of four transitional zones became much more irregular and the numbers of tidemark was occasionally increased with granulomatous tissue. The pathogenesis of the rotator cuff tear can be ascribed to the combination of aging, enthesopathy, inherent property of the supraspinatus tendon, injury and subacromial impingement.     

Healing of full-thickness tears of avian supracoracoid tendons: in situ hybridization of alpha1(I) and alpha1(III) procollagen mRNA.

Although clinically significant, much remains unknown about the healing of the torn rotator cuff tendon, because of unavailability of appropriate animal model. The human supraspinatus tendon faces the subacromial bursa superiorly, and the joint capsule inferiorly, while the digital flexor tendon is surrounded by the synovium. We hypothesized that the supraspinatus tendon heals by the process which is different from that observed with digital flexor tendons, in which epitenon cells migrate into the torn portion circumferentially. The avian supracoracoid tendon was adopted for this experiment because of its similarity to the human supraspinatus tendon. We developed a full-thickness tendon laceration followed by primary suture. The objective of this study was to detect localization of the responsible cells for repair of the tendon. We examined the process using histology and in situ hybridization. Starting at week 1 the peritendon cells of the bursal side proliferated and migrated into the laceration site. At week 6, the tendon stumps were continuous with new connective tissue. High-level expression of procollagen mRNA in the proliferating peritendon cells on the bursal side demonstrates to contribute to the reparative process, which progressed to the joint side. This mode of repair is different from that of the digital flexor tendon.     

Apoptosis in rotator cuff tendonopathy.

The aim of this study was to investigate the involvement of apoptosis (programmed cell death) in the pathogenesis of rotator cuff disorders. The edges of torn supraspinatus rotator cuff tendons were collected from patients with rotator cuff tear (n = 25). Samples of the intra-articular portion of subscapularis tendons were collected from patients without rotator cuff tear as control (n = 6). To minimize individual variance, we also collected six pairs of supraspinatus tendon and subscapularis tendon from six patients with rotator cuff tears. Apoptosis was detected by in situ DNA end labelling assay and DNA laddering assay. Immunohistochemical staining was performed to identify cells undergoing apoptosis. Control subscapularis tendon had normal morphology. Tendon from torn supraspinatus rotator cuff showed significant mucoid degeneration. Within the areas of degeneration, there were large numbers of apoptotic cells. The percentage of apoptotic cells in the degenerative rotator cuff (34%) was significantly higher than that in controls (13%) (p < 0.001). The excessive apoptosis detected in degenerative rotator cuff tissue was confirmed by DNA laddering assays. This is the first report of excessive apoptosis in degenerating rotator cuff tendon. Cells undergoing apoptosis in rotator cuff were mainly fibroblast-like cells. These finding indicate that apoptosis may play an important role in the pathogenesis of rotator cuff degeneration.     

Inhomogeneous mechanical behavior of the human supraspinatus tendon under uniaxial loading.

Disorders of the rotator cuff, particularly tears of the rotator cuff tendons, cause significant shoulder disability. Among numerous factors thought to be responsible for the initiation and progression of supraspinatus tears are those related to the tendon's biomechanical properties. We hypothesized that in supraspinatus tendons subjected to tensile loading a strain gradient (difference) exists between the articular and bursal tendon surfaces, that regional strain differences exist on each of these two tendon surfaces, and that tendon surface strains vary with glenohumeral abduction. To test these hypotheses, the intrinsic inhomogeneous deformational characteristics of the articular and bursal surfaces of eight intact human cadaveric supraspinatus tendons were studied at three glenohumeral abduction angles using a novel multiple strain measuring system which simultaneously recorded surface marker displacements on two opposing soft tissue surfaces. Under applied tensile loads, the articular surface exhibited greater strain at 22 degrees (7.4+/-2.6% vs. 1.3+/-0.7%, p=0.0002) and 63 degrees (6.4+/-1.6% vs. 2.7+/-1.2%, p=0.0001) whereas the bursal surface exhibited greater strain at 90 degrees (7.6+/-2.8% vs. 4.9+/-0.4%, p=0.013). At all abduction angles, insertion strains were higher than those of the mid-tendon and tendon-muscle junction regions. The existence of inhomogeneous surface strains in the intact supraspinatus tendon demonstrates that intratendinous shear occurs within the tendon. The higher strain on the articular side of the tendon, especially at the insertion region, suggests a propensity for tears to initiate in the articular tendinous zone.     

Effect of glenohumeral abduction angle on the mechanical interaction between the supraspinatus and infraspinatus tendons for the intact,partial‐thickness torn,and repaired supraspinatus tendon conditions

Rotator cuff tears are difficult to manage because of the structural and mechanical inhomogeneity of the supraspinatus tendon. Previously, we showed that with the arm at the side, the supraspinatus and infraspinatus tendons mechanically interact such that conditions that increase supraspinatus tendon strain, such as load or full‐thickness tears, also increase infraspinatus tendon strain. This suggests that the infraspinatus tendon may shield the supraspinatus tendon from further injury while becoming at increased risk of injury itself. In this study, the effect of glenohumeral abduction angle on the interaction between the two tendons was evaluated for supraspinatus tendon partial‐thickness tears and two repair techniques. Principal strains were quantified in both tendons for 0°, 30°, and 60° of glenohumeral abduction. Results showed that interaction between the two tendons is interrupted by an increase in abduction angle for all supraspinatus tendon conditions evaluated. Infraspinatus tendon strain was lower at 30° and 60° than at 0° abduction angle. In conclusion, interaction between the supraspinatus and infraspinatus tendons is interrupted with increase in abduction angle. Additionally, 30° abduction should be further evaluated for management of rotator cuff tears and repairs as it is the angle at which both supraspinatus and infraspinatus tendon strain is decreased. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:846–851, 2010     

Comparing normal and torn rotator cuff tendons using dynamic shear analysis

This study reports the application of a novel method for quantitatively determining differences in the mechanical properties of healthy and torn rotator cuff tissues. In order to overcome problems of stress risers at the grip-tendon interface that can obscure mechanical measurements of small tendons, we conducted our investigation using dynamic shear analysis. Rotator cuff tendon specimens were obtained from 100 patients during shoulder surgery. They included 82 differently sized tears and 18 matched controls. We subjected biopsy samples of 3 mm in diameter to oscillatory deformation under compression using dynamic shear analysis. The storage modulus (G') was calculated as an indicator of mechanical integrity. Normal tendons had a significantly higher storage modulus than torn tendons, indicating that torn tendons are mechanically weaker than normal tendons (p = 0.003). Normal tendons had a significantly higher mean shear modulus than tendons with massive tears (p < 0.01). Dynamic shear analysis allows the determination of shear mechanical properties of small tissue specimens obtained intra-operatively that could not be studied by conventional methods of tensile testing. These methods could be employed to investigate other musculoskeletal tissues. This pilot study provides some insight into mechanisms that might contribute to the failure of repair surgery, and with future application could help direct the most appropriate treatment for specific rotator cuff tears.     

Strain distribution due to propagation of tears in the anterior supraspinatus tendon

Rotator cuff tears are a significant clinical problem. Tears in the anterior supraspinatus might behave differently compared to central tears due to differences in regional structural properties. The objective of this study was to determine strain distributions for anterior supraspinatus tendon tears and the relationship to tear propagation during cyclic loading. It was hypothesized that highest maximum principal strain would be posterior to the tear, and tears would propagate in the direction of the maximum principal strain. Eight human cadaveric supraspinatus tendons with surgically created small tears in the anterior third were tested with increasing levels of cyclic loads. The position of strain markers was recorded on the bursal surface of the tendon to calculate strain. Tendons reached a 2 cm critical tendon retraction at 580 ± 181 N. Largest strains were found medial and posterior to the tear (26.1 ± 9.4%). In five tendons, the strain direction for the initial (114 ± 28°) and final loading sets (86 ± 20°) indicated the strain direction shifted from an anterior to posterior orientation (p < 0.01), corresponding to the direction of tear propagation. Based on the results, anterior supraspinatus tears would remain isolated to the supraspinatus tendon during activities of daily living. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1283–1289, 2014.     

Effects of lidocaine on torn rotator cuff tendons

We determined lidocaine's action on torn rotator cuff tendons in vitro and in vivo. For in vitro experiments, cell proliferation and viability assays were performed using tenocytes derived from human torn rotator cuff tendons. For in vivo experiments, acute rotator cuff tears were made on the supraspinatus tendons in the rats’ bilateral shoulders; before closure, lidocaine was injected into the shoulder and saline into the contralateral shoulder (control). After sacrifice, the specimens underwent biomechanical testing or histological analysis at 24 h and at 2, 4, and 8 weeks after surgery. The extent of collagen organization and apoptosis were semi‐quantitatively evaluated using collagen picrosirius red staining. Apoptosis was examined using TUNEL staining and electron microscopy. Cell proliferation decreased dose‐dependently. After exposure to 0.1% lidocaine for 24 h, cell viability decreased. Two and 4 weeks after surgery, the ultimate load to failure decreased more in the lidocaine group than in the control group, with significantly reduced stiffness in the lidocaine group 2 weeks after surgery. Collagen organization significantly decreased in the lidocaine group by 4 weeks after surgery but returned to baseline at 8 weeks. TUNEL staining detected numerous apoptotic tenocytes at the torn tendon edge exposed to lidocaine 24 h after surgery; electron microscopy confirmed the condensed cell nuclei. These changes were not observed in controls. Lidocaine caused cytotoxicity to tenocytes under both conditions, decreased biomechanical properties, and induced apoptosis and delay of collagen organization in this model. Subacromial lidocaine injections in patients with rotator cuff tears should be performed carefully. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1620–1627, 2016.     

Glenoid cartilage mechanical properties decrease after rotator cuff tears in a rat model

Rotator cuff repairs are commonly performed to reduce pain and restore function. Tears are also treated successfully without surgical intervention; however, the effect that a torn tendon has on the glenohumeral cartilage remains unknown. Clinically, a correlation between massive rotator cuff tears and glenohumeral arthritis has often been observed. This may be due to a disruption in the balance of forces at the shoulder, resulting in migration of the humeral head and subsequently, abnormal loading of the glenoid. Our lab previously demonstrated changes in ambulation and intact tendon mechanical properties following supraspinatus and infraspinatus rotator cuff tendon tears in a rat model. Therefore, the purpose of this study was to investigate the effects of supraspinatus and infraspinatus rotator cuff tears on the glenoid cartilage. Nine rats underwent unilateral detachment of the supraspinatus and infraspinatus tendons and were sacrificed after 4 weeks. Cartilage thickness significantly decreased in the antero‐inferior region of injured shoulders. In addition, equilibrium elastic modulus significantly decreased in the center, antero‐superior, antero‐inferior, and superior regions. These results suggest that altered loading after rotator cuff injury may lead to damage to the joint with significant pain and dysfunction. Clinically, understanding the mechanical processes involved with joint damage will allow physicians to better advise patients. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1435–1439, 2012     

Arthroscopic Intratendinous Repair of the Delaminated Partial-Thickness Rotator Cuff Tear in Overhead Athletes

A distinct type of partial-thickness rotator cuff tear has been observed in overhead athletes, characterized by partial failure of the undersurface of the posterior supraspinatus and anterior infraspinatus tendons with intratendinous delamination. We present a technique of percutaneous intratendinous repair using nonabsorbable mattress sutures designed for the management of articular-side delaminated partial-thickness tears. After tear evaluation and preparation, the torn rotator cuff undersurface is held in a reduced position with a grasper through an anterolateral rotator interval portal while viewing intra-articularly. Two spinal needles are then placed percutaneously through the full thickness of the torn and intact rotator cuff. A polydioxanone suture is passed through each needle, retrieved out the anterior portal, and used to shuttle a single nonabsorbable No. 2 suture through the tissue, creating a mattress suture. Multiple mattress sutures can be placed as dictated by tear size and morphology, with suture retrieval and knot securing then proceeding in the subacromial space. We have adopted this approach with the goals of anatomically re-establishing the rotator cuff insertion and sealing the area of intratendinous delamination while preventing significant alteration to the anatomy of the rotator cuff insertion, which could lead to motion deficits, internal impingement, and potential tear recurrence.     

Oxidative stress-induced c-Jun N-terminal kinase (JNK) activation in tendon cells upregulates MMP1 mRNA and protein expression.

To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons was evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and Western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 overexpression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.     

Rotator cuff defect healing: A biomechanical and histologic analysis in an animal model

Rotator cuff tears are one of the most common causes of pain and disability in the upper extremity. With the use of an animal model, we studied the healing response of a controlled defect in the normal supraspinatus tendon and in a tendon with a reduced intrinsic healing capacity. In 36 Sprague-Dawley rats, defects (2 mm × 2 mm) were created in the supraspinatus tendons bilaterally. To model a tendon with an intrinsically reduced capacity to heal, the tissue adjacent to the defect area in the left shoulder was treated with in situ freezing. The contralateral tendon was not frozen. After 3 (n = 12), 6(n = 12), and 12(n = 12) weeks, animals were killed and underwent histologic (n = 4 from each group) and biomechanical (n = 8 from each group) evaluation. An additional group of untreated animals served as a normal control group. On histologic evaluation 78% of tendons had persistent defects (defined as incomplete closure of the defect site). Over time, the tissue from both groups demonstrated an improved histologic grade but did not reach normal levels, even at 12 weeks. No histologic differences were found between defect healing in normal tendons and in those treated with in situ freezing. On biomechanical evaluation there were also no significant differences between treatment groups. Over time, an improvement occurred in tissue properties, indicating that some healing of the defects had occurred. However, these tissue properties remained an order of magnitude lower than those of normal control tendons. These findings indicate that there is an active but inadequate repair response to the defect in the rat supraspinatus tendon, which is not significantly worsened by in situ freezing of the tissue around the defect. This model has applications     

Supraspinatus tendon repair into a bony trough in the rabbit: Mechanical restoration and correlative imaging

Recurrence of tears is a common complication after rotator cuff surgery. Retearing seems to occur early after surgery and may be attributed to too early or too vigorous exercises. We found no experimental data correlating the strength of the rotator cuff early after surgery and imaging. Our objectives were to measure the peak load to failure of rabbit supraspinatus tendon–bone constructs at early times postoperatively, to determine their mode of failure, and to determine whether computed tomography (CT) can predict their strength. We divided one supraspinatus tendon of 40 adult female white New Zealand rabbits and, after resection of the enthesis, sutured the tendon into a bony trough. Ten rabbits were killed immediately and 10 each at 1, 2, and 6 weeks postoperatively. The explanted tendons of both shoulders were imaged on CT and tested to failure. Compared to normal tendons (mean 210 ± 42 N), the mean strength was very low at 0 weeks (57 ± 21 N) and 1 week (86 ± 33 N) (both p < 0.05); it had recovered by 6 weeks (324 ± 66 N). Early on, suture pullout was the most common mode of failure, whereas at 6 weeks, mid‐substance tears predominated (p < 0.05). Hypoattenuation on CT was associated with increased strength of the tendon–bone construct (p < 0.05). The strength of the surgical construct is very low in the early postoperative period. Therefore, the shoulder should be submitted only to loads not interfering with healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:710–715, 2010     

Outcome of pectoralis major transfer for the treatment of irreparable subscapularis tears

BACKGROUND: Chronic tears of the subscapularis tendon with or without associated tears of the supraspinatus and infraspinatus tendons may lead to pain and dysfunction of the shoulder. If conservative treatment fails and repair of the musculotendinous unit is impossible, transfer of the pectoralis major tendon can be attempted to substitute for lost subscapularis function. METHODS: Twenty-eight patients underwent a total of thirty consecutive pectoralis major transfers at an average age of fifty-three years. There were twelve isolated subscapularis tears and eighteen subscapularis tears associated with a tear of the supraspinatus or the supraspinatus and infraspinatus. All patients were examined clinically and with standard radiographs. RESULTS: The mean relative Constant score increased from 47% preoperatively to 70% at an average of thirty-two months postoperatively (p < 0.0001). The mean Constant scores for pain (p = 0.0009) and activities of daily living (p < 0.0001), the range of forward flexion (p < 0.05), and abduction strength (p = 0.001) also improved. Thirteen patients (14 shoulders) were very satisfied, ten patients (eleven shoulders) were satisfied, two patients (two shoulders) were disappointed, and three patients (three shoulders) were dissatisfied with the result. The average subjective shoulder value increased from 23% preoperatively to 55% postoperatively (p = 0.0009). In patients with a massive tear, the outcome was less favorable when the torn supraspinatus tendon was irreparable, as determined preoperatively or intraoperatively, than when it was reparable (average relative Constant scores, 49% and 79%, respectively; p = 0.002). CONCLUSIONS: Pectoralis major transfer results in improvement for patients with an irreparable subscapularis tear with or without an associated reparable supraspinatus tear. If an irreparable subscapularis tear is associated with an irreparable supraspinatus tear, the results are less favorable, and pectoralis major transfer may not be warranted.     

Acromial spur: relationship to aging and morphologic changes in the rotator cuff

This study's objective is to elucidate the relationship between acromial spur formation and rotator cuff pathology or aging. The subjects comprised 1029 shoulders in control, cadaveric, and operative groups. A radiograph in the supraspinatus outlet view was taken in all subjects. The lengths of the incident spurs were measured and classified into 3 sizes (small, <5 mm; medium, <10 mm; and large, > or =10 mm). The rotator cuff was macroscopically classified as normal or as having bursal-side fraying, joint-side tear, intratendinous tear, bursal-side tear, complete tear limited to the supraspinatus tendon, or massive tear. In the control group, the overall incidence of spurs and spur size increased with advancing age (P < .001), but the majority of spurs were small (<5 mm). In the cadaveric group, the overall incidence did not correlate with advancing age (P > .05). However, spur size increased with age in subjects aged 50 years or older (P < .001). The incidence of spurs in rotator cuffs with bursal-side tears was highest and was significantly higher than that in normal cuffs and cuffs with bursal-side fraying and intratendinous tears. We observed 40% of medium spurs and 69% of large spurs in cases with bursal-side tears, complete tears limited to the supraspinatus tendon, and massive tears. In the operative group, the overall incidence correlated to advancing age (P < .001), reaching 80% or more in subjects aged 30 years or older. In addition, the size of spurs was larger than that in the other 2 groups in all age groups with few exceptions (P < .05). Small spurs were associated with advancing age. Morphologic change to the bursal side of the rotator cuff may enhance spur growth. The presence of a small spur has no diagnostic value for rotator cuff tears. Spurs measuring 5 mm or more, however, are of diagnostic value because of their high rate of association with bursal-side tear, complete tears limited to the supraspinatus tendon, or massive tears.     

Functional outcome of arthroscopic rotator cuff repairs: a correlation of anatomic and clinical results

Even though several studies have revealed excellent clinical results with arthroscopic repair of rotator cuff tendons, poor healing of the repair and retearing of the tendon occur in many cases. Patterns of outcome correlating functional capacity and anatomic integrity of the repaired rotator cuff are not well defined. The goal of this prospective study was to determine the pattern of anatomic and functional outcomes among patients undergoing single-row arthroscopic rotator cuff repair. This study confirmed that single-row arthroscopic repair of small- and medium-sized supraspinatus tendon tears significantly improves rotator cuff integrity and functional outcomes. A completely healed tendon was observed in 60% of the cases. Age is a predictor of cuff integrity after the operation. Functional improvement was greater and significant in patients with complete healing at follow-up; however, a recurrent tear did not preclude positive functional results.     

Cystic changes of the humeral head on MR imaging: Relation to age and cuff-tears

We obtained MR images of 140 painful shoulders in 134 patients to determine the relationship between cystic changes of the humeral head and integrity of the rotator cuff. Cystic changes were observed in 49 shoulders (35%) and the commonest site was in the bare bone area of the anatomical neck, and the second commonest site was at the attachment of the supraspinatus tendon. Cystic changes in the bare bone area were observed equally often in shoulders with or without rotator cuff tears (27% and 18%, respectively) and were more frequently observed in the elderly. Cystic changes at the attachment of the supraspinatus and subscapularis tendons were specific to rotator cuff tears: they were observed in 28% of rotator cuff tears, but in none of those with an intact cuff.

We conclude that there are two distinct types of cystic changes: one at the attachment of the supraspinatus and subscapularis tendons, which is closely related to tears of these tendons, and the other in the bare bone area of the anatomical neck, which is related to aging.