Objectives . The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. . Methods . Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. . Results. Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. . Conclusions . These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61

Aims. Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Methods. Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically. Results. Histological analysis of supraspinatus muscle showed that HIIT improved muscle atrophy, fatty infiltration, and contractile force compared to the no exercise group. In the HIIT groups, supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat showed increased expression of tyrosine hydroxylase and uncoupling protein 1, and upregulated the β3AR thermogenesis pathway. However, the effect of HIIT was not present in mice injected with SR59230A, suggesting that HIIT affected muscles via β3AR. Conclusion. HIIT improved supraspinatus muscle quality and function after rotator cuff tears by activating systemic sympathetic nerve fibre near adipocytes and β3AR. Cite this article: Bone Joint Res 2023;12(8):455–466

Aims. Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484

Interstitial supraspinatus tears can cause persistent subacromial impingement symptoms despite non operative treatment. Autologous tendon cell injection (ATI) is a non-surgical treatment for tendinopathies and tear. We report a randomised controlled study of ATI compared to corticosteroid injection (CS) as treatment for interstitial supraspinatus tears and tendinopathy. Inclusion criteria were patients with symptom duration > 6 months, MRI confirmed intrasubstance supraspinatus tear, and prior treatment with physiotherapy and ≥ one CS or PRP injection. Participants were randomised to receive ATI to the interstitial tear or corticosteroid injection to the subacromial bursa in a 2:1 ratio, under ultrasound guidance. Assessments of pain (VAS) and function (ASES) were performed at baseline, and 1, 3, 6 and 12 months post treatment. 30 participants (19 randomised to ATI) with a mean age of 50.5 years (10 females) and a mean duration of symptoms of 23.5 months. Baseline VAS pain and ASES scores were comparable between groups. While mean VAS pain scores improved in both groups at 3 months after treatment, pain scores were superior with ATI at 6 months (p=0.01). Mean ASES scores in the ATI group were superior to the CS group at 3 months (p=0.026) and 6 months (p=0.012). Seven participants in the CS group withdrew prior to 12 months due to lack of improvement. At 12 months, mean VAS pain in the ATI group was 1.6 ± 1.3. The improvements in mean ASES scores in the ATI group at 6 and 12 months were greater than the MCID (12.0 points). At 12 months, 95% of ATI participants had an ASES score > the PASS (patient acceptable symptom state). This is the first level one study using ATI to treat interstitial supraspinatus tear. ATI results in a significant reduction in pain and improvement in shoulder function

Aims. Rotator cuff (RC) tears are common musculoskeletal injuries which often require surgical intervention. Noninvasive pulsed electromagnetic field (PEMF) devices have been approved for treatment of long-bone fracture nonunions and as an adjunct to lumbar and cervical spine fusion surgery. This study aimed to assess the effect of continuous PEMF on postoperative RC healing in a rat RC repair model. Methods. A total of 30 Wistar rats underwent acute bilateral supraspinatus tear and repair. A miniaturized electromagnetic device (MED) was implanted at the right shoulder and generated focused PEMF therapy. The animals’ left shoulders served as controls. Biomechanical, histological, and bone properties were assessed at three and six weeks. Results. Extension of the tendon from preload to the maximum load to failure was significantly better in the PEMF-treated shoulders at three weeks compared to controls (p = 0.038). The percentage strain was significantly higher in the PEMF group at both timepoints (p = 0.037). Collagen organization was significantly better (p = 0.034) as was tissue mineral density in the PEMF-treated group at three weeks (p = 0.028). Tendon immunohistochemistry revealed a prominent increase in type I collagen at the repair site at three weeks following continuous PEMF treatment compared with controls. None of the other tested parameters differed between the groups. Conclusion. MED-generated PEMF may enhance early postoperative tendon-to-bone healing in an acute rat supraspinatus detachment and repair model. Superior biomechanical elasticity parameters together with better collagen organization suggest improved RC healing. Cite this article: Bone Joint Res 2021;10(5):298–306

Massive posterosuperior cuff tears (mRCT) retracted to the glenoid are surgically challenging and often associated with high retear rates. Primary repair is a less-favourable option and other salvage procedures such as SCR and tendon transfers are used. This study presents clinical and radiological outcomes of muscle advancement technique for repair of mRCT. Sixty-one patients (mean age 57±6, 77% males and 23% females) (66 shoulders) underwent all-arthroscopic rotator cuff repair that included supraspinatus and infraspinatus subperiosteal dissection off scapular bony fossae, lateral advancement of tendon laminae, and tension-free double-layer Lasso Loop repair to footprint. Pre-and post-operative range of motion (ROM), cuff strength, VAS, Constant, ASES, and UCLA scores were assessed. Radiologic assessment included modified Patte and Goutallier classifications. All patients had MRI at 6 months to evaluate healing and integrity of repair was assessed using Sugaya classification with Sugaya 4 and 5 considered retears. Advanced fatty degeneration (Goutallier 3-4) was present in 44% and 20% of supraspinatus and infraspinatus. Tendon retraction was to the level of or medial to glenoid in 22%, and just lateral in 66%. 50.8% mRCT extended to teres minor. Subscapularis was partially torn (Lafosse 1-3) in 46% and completely torn (Lafosse 4-5) in 20%. At mean follow-up (52.4 weeks), a significant increase in ROM, Relative Cuff Strength (from 57% to 90% compared to contralateral side), VAS (from 4 ±2.5 to 1±1.7), Constant (50±17.8 to 74 ±13.0), ASES (52 ±17.5 to 87 ±14.9), and UCLA (16± 4.9 to 30 ±4.9) scores were noted. There were six retears (10%), one failure due to P. acnes infection. 93% returned to pre-injury work and 89% of cases returned to pre-injury sport. Satisfaction rate was 96%. Muscle advancement technique for mRCT is a viable option with low retear rates, restoration of ROM, strength, and excellent functional outcomes

16 to 34% of the population suffer from shoulder pain, the most common cause being rotator cuff tears. NICE guidance recommends using ultrasound scan (USS) or MRI to assess these patients, but does not specify which is preferable. This study assesses the accuracy of USS and MRI in rotator cuff tears in a DGH, to establish the most appropriate imaging modality. Patients who had at least two of shoulder ultrasound, MRI or arthroscopy within a seven month period (n=55) were included in this retrospective study. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were calculated using arthroscopy as the true result, and kappa coefficients calculated for each pairing. 59 comparisons were made in total. Sensitivity for MRI in full supraspinatus tears was 0.83, and for USS 0.75. Specificity for MRI in these tears was 0.75, and for USS 0.83. Values were much lower in other tears, which occurred less frequently. USS and MRI completely agreed with each other 61.3% of the time. Both modalities were only completely accurate 50% of the time. Kappa coefficient between arthroscopy and MRI for supraspinatus tears was 0.658, and for USS was 0.615. There was no statistical difference between MRI and USS sensitivity or specificity (p=1), suggesting that one modality cannot be recommended over the other for full supraspinatus tears. They also do not tend to corroborate one another, suggesting that there is no benefit from doing both scans. Further research is needed to see how both modalities can be improved to increase their accuracy

Aims. The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. Methods. In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts. Results. Rotator cuff muscle volume was significantly decreased in patients with OA, CTA, and IRCT compared to healthy patients (p < 0.0001). Atrophy was comparable for all muscles between CTA, IRCT, and OA patients, except for the supraspinatus, which was significantly more atrophied in CTA and IRCT (p = 0.002). In healthy shoulders, the anterior cuff represented 45% of the entire cuff, while the posterior cuff represented 40%. A similar partition between anterior and posterior cuff was also found in both CTA and IRCT patients. However, in OA patients, the relative volume of the anterior (42%) and posterior cuff (45%) were similar. Conclusion. This study shows that rotator cuff muscle volume is significantly decreased in patients with OA, CTA, or IRCT compared to healthy patients, but that only minimal differences can be observed between the different pathological groups. This suggests that the influence of rotator cuff muscle volume and atrophy (including intramuscular fat) as an independent factor of outcome may be overestimated. Cite this article: Bone Jt Open 2021;2(7):552–561

We hypothesised that diet-induced obesity (DIO) would result in inferior enthesis healing in a rat model of rotator cuff (RC) repair and that dietary intervention in the peri-operative period would improve enthesis healing. A total of 78 male Sprague-Dawley rats were divided into three weight-matched groups from weaning and fed either: control diet (CD), high-fat diet (HFD), or HFD until surgery, then CD thereafter (HF-CD). After 12 weeks, the left supraspinatus tendon was detached, followed by immediate surgical repair. At 2 and 12 weeks post-surgery, animals were culled, and RCs harvested for biomechanical and histological evaluation. Body composition and metabolic markers were assessed via DEXA and plasma analyses, respectively. DIO was established in the HFD and HF-CD groups before surgery and subsequently reversed in the HF-CD group after surgery. Histologically, the appearance of the repaired entheses was poorer in both the HFD and HF-CD groups compared with the CD group at 12 weeks after surgery, with semiquantitative scores of 6.2 (P<0.01), 4.98 (P<0.01), and 8.7 of 15, respectively. The repaired entheses in the HF-CD group had a significantly lower load to failure (P=0.03) at 12 weeks after surgery compared with the CD group, while the load to failure in the HFD group was low but not significantly different (P=0.10). Plasma leptin were negatively correlated with histology scores and load to failure at 12 weeks after surgery. DIO impaired enthesis healing in this rat RC repair model, with inferior biomechanical and histological outcomes. Restoring normal weight with dietary change after surgery did not improve healing outcomes. Circulating levels of leptin significantly correlated with poor healing outcomes. This pre-clinical rodent model demonstrates that obesity is a potentially modifiable factor that impairs RC healing and increases the risk of failure after RC surgery

Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model. A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site. In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity. This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem

Introduction. We aim to assess whether radiographic characteristics of the greater tuberosity fragment can predict rotator cuff tears inpatients with anterior shoulder dislocations combined with an isolated fracture of the greater tuberosity. Methods. A retrospective single-centre case series of 61 consecutive patients that presented with anterior shoulder dislocations combined with an isolated fracture of the greater tuberosity between January 2018 and July 2022. Inclusion criteria: patients with atraumatic anterior shoulder dislocation associated with an isolated fracture of the greater tuberosity with a minimum follow-up of 3-months. Exclusion criteria: patients with other fractures of the proximal humerus or glenoid. Rotator cuff tears were diagnosed using magnetic resonance or ultrasound imaging. Greater tuberosity fragment size and displacement was calculated on plain radiographs using validated methods. Results. The case series was composed of 22 men and 39 women with a mean age of 65 years (29 - 91 years). The mean follow-up was 15months and median follow up 8.5 months (3 – 60 months). A rotator cuff tear was diagnosed in 14 patients (16%) and involved the supraspinatus (13), infraspinatus (4) and subscapularis (2). Full-thickness tears occurred in 6 patients and partial-thickness tears in 8patients. The mean time from initial injury to rotator cuff tear diagnosis was 5 months (2 – 22 months). The mean greater tuberosity fragment length was 23.4 mm in rotator cuff tear patients versus 32.6 mm in those without a tear (p = 0.006, CI: -15 - -2). The mean greater tuberosity. fragment width was 11.1 mm in rotator cuff tear patients versus 17.8 mm in those without a tear (p = 0.0004, CI: -10 - -2). There was no significant difference in the super inferior and anteroposterior fragment displacement between the two groups. Conclusion. In patients with shoulder dislocations combined with an isolated fracture of the greater tuberosity, rotator cuff tears are associated with a smaller sized greater tuberosity fragment

Obesity is associated with poor outcomes and increased risk of failure after rotator cuff (RC) repair surgery. The effect of diet-induced obesity (DIO) on enthesis healing has not been well characterised and whether its effects can be reversed with dietary intervention is unknown. We hypothesised that DIO would result in inferior enthesis healing in a rat model of RC repair and that dietary intervention in the peri-operative period would improve enthesis healing. A total of 78 male Sprague-Dawley rats were divided into three weight-matched groups from weaning and fed either: control diet (CD), high-fat diet (HFD), or HFD until surgery, then CD thereafter (HF-CD). After 12 weeks the left supraspinatus tendon was detached, followed by immediate surgical repair. At 2 and 12 weeks post-surgery, animals were cullers and RCs harvested for biomechanical and histological evaluation. Body composition and metabolic markers were assessed via DEXA and plasma analyses, respectively. DIO was established in the HFD and HF-CD groups prior to surgery, and subsequently reversed in the HF-CD group after surgery. At 12 weeks post-surgery, plasma leptin concentrations were higher in the HFD group compared to the CD group (5.28 vs. 2.91ng/ml, P=0.003). Histologically, the appearance of the repaired entheses was poorer in both the HFD and HF-CD compared to the CD group at 12 weeks (overall histological score 6.20 (P=0.008), 4.98 (P=0.001) and 8.68 out of 15, respectively). The repaired entheses in the HF-CD group had significantly lower (26.4 N, P=0.028) load-at-failure 12 weeks post-surgery compared to the CD group (34.4 N); while the HFD group was low, but not significantly different (28.1 N, P=0.096). Body mass at the time of surgery, plasma leptin and body fat percentage were negatively correlated with histological scores and plasma leptin with load-at-failure 12 weeks post-surgery. DIO impaired enthesis healing in this rat RC repair model, with inferior biomechanical and histological outcomes. Restoring normal weight with dietary change after surgery did not improve healing outcomes. Exploring interventions that improve the metabolic state of obese patients and counselling patients appropriately about their modest expectations after repair should be considered

The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations

Summary Statement. Tendon-bone interface becomes matured with the perforating fiber and the cells striding over the bone area. We suggest that both “perforating fiber” and “cell stride” could play a crucial role in regeneration after rotator cuff repair. Introduction. To obtain a successful outcome after rotator cuff repair, repaired tendon requires to be anchored biologically to the bone. However, it is well known that the histological structure of the repaired tendon-bone insertion is totally different from the normal insertion. This morphological alteration may contribute to biological instability after surgical repair. To address these issues, it is fundamental to clarify the difference of the structure between the normal and the repaired insertion in detail. Surprisingly, few studies on the tendon-bone insertion using electron microscopy has been performed so far, since the insertion area is solid (bone/cartilage) and extremely limited for the analysis. Recently, a new scanning electron microscopical method (FIB/SEM tomography) has been developed, making it possible to analyze the wider area with the higher resolution and reconstruct 3D ultrastructures. The purpose of this study was to analyze the ultrastructure of the repaired supraspinatus tendon-bone insertion in rat using FIB/SEM tomography. Materials and Methods. Adult Sprague-Dawley rats underwent complete cuff tear and subsequent repair of the supraspinatus tendon. The repaired supraspinatus tendon-bone interface was evaluated at 2 and 4 weeks after surgery. At each time point, 6 shoulders were used for biomechanical testing (ultimate load-to-failure and linear stiffness), 3 shoulders for conventional histological analysis and 3 shoulders for the ultrastructural analysis. The supraspinatus tendon insertion of the age-matched adult SD rats was used as normal control. For statistical analysis, the Wilcoxon's rank sum test was used to compare load-to-failure and linear stiffness. Differences of P<0.05 were considered significant. Results. <Biomechanical testing> All shoulders failed at the tendon-bone interface. The ultimate load-to-failure and the linear stiffness were significantly greater at 8 weeks than at 4 weeks (p<0.05). Normal tendon-bone insertion: The normal supraspinatus insertion consists of four-layered structure: tendon, fibrocartilage, mineralised fibrocartilage and bone. Repaired tendon-bone interface. At week 2, the fibro-vascular tissue was intervened between the tendon and bone at the repaired site. At week 4, the fibro-vascular tissue became organised, and perforating fibers were partially observed. <Ultrastructure using FIB/SEM tomography> Normal tendon-bone insertion: The ultrastructure of the normal supraspinatus insertion was very smooth. The cells were located between collagen bundles and arranged with their cell processes parallel to the bundles. Repaired tendon-bone interface: At week 2, the cells in the fibro-vascular tissue were arranged irregularly. At week 4, a part of the cells became arranged regularly and participated in linkage between the fibro-vascular tissue and bone, striding their processes across the bone side. Apparent boundary separating the fibro-vascular tissue from bone was observed throughout the periods. Conclusion. At 4 weeks after surgery, the repaired supraspinatus insertion remains to be immature and biologically weak. At 8 weeks after the surgery, it becomes matured with the perforating fiber and the cells striding over the bone area. We therefore suggest that both “perforating fiber” and “cell stride” could play a crucial role in regeneration of the tendon-bone interface after rotator cuff repair

Excessive apoptosis has been found in torn supraspinatus tendon1 and mechanically loaded tendon cells2. Following oxidative and other forms of stress, one family of proteins that is often unregulated are Heat Shock Proteins (HSPs). The purpose of this study was to determine if HSPs were unregulated in human and rat models of tendinopathy and to determine if this was associated with increased expression of regulators of apoptosis (cFLIP, Caspases 3& 8). A running rat supraspinatus tendinopathy overuse model 3 was used with custom microarrays consisting of 5760 rat oligonucleotides in duplicate. Seventeen torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery and evaluated using semiquantative RT-PCR and immunohistochemistry. Rat Microarray: Upregulation of HSP 27 (×3.4) & 70 (×2.5) and cFLIP (×2.2) receptor was noted in degenerative rat supraspinatus tendon subjected to daily treadmill running for 14 days compared to tendons of animals subject to cage activity only. Histological analysis: All torn human supraspinatus tendons exhibited changes consistent with marked tendinopathy. Matched subscapularis tendon showed appearances of moderate-advanced degenerative change. Apoptosis mRNA expression: The expression levels of caspase 3 & 8 and HSPs 27 & 70 were significantly higher in the torn edges of supraspinatus when compared to matched subscapularis tendon and control tendon (p< 0.01). cFLIP showed significantly greater (p< 0.001) expression in matched subscapularis compared to supraspinatus and control tendon. Immunohistochemical analysis: cFLIP, Caspase 3 & 8 and HSP 27 and 70 was confirmed in all samples of torn supraspinatus tendon. Significantly increased immunoactivity of Caspase 3& 8 and HSP 27 & 70 were found in torn supraspinatus (p< 0.001) compared to matched and normal subscapularis. The proteins were localized to tendon cells. The finding of significantly increased levels of Heat Shock Proteins in human and rat models of tendinopathy with the co-expression of other regulators of apoptosis suggests that Heat Shock Proteins play a role in the cascade of stress activated-programmed cell death and degeneration in tendinopathy

Introduction. Many literatures regarding more specific tests to diagnose the supraspinatus tendon injuries and the best rehabilitation methods to strengthen the supraspinatus have been published. However, conflicting results have been reported. 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography (PET) has been recently used to assess skeletal muscle activities in various fields. Purpose. To evaluate & compare the metabolic activities of deltoid & rotator cuff muscles after the full-can & empty-can exercises using PET-CT. Materials and Methods. Ten healthy volunteers (age 27–34/mean 29.8 ± 2.7) with no history of shoulder pain and diabetes mellitus participated in this study. After FDG injection, both arms were maintained in the position of empty can and full can for ten minutes respectively. PET-CT was performed at forty minutes after the injection. The maximum standardized uptake value (SUV) was measured in the anterior, middle and posterior deltoid, supraspinatus, subacapularis and infraspinauts on the entire axial images. Results. The middle deltoid and subscapularis showed significantly greater activity during the empty-can exercise than during the full-can exercise (P=.006 and P=.003 respectively). The muscular activity of the supraspinatus also increased during the empty-can exercise than during the full-can exercise, although no statistical difference existed between two exercises. Six cases of eight cases who had increased activity of the subscapularis had increased activity in superior one half of the subscapularis than in lower one half of it, although there is no significant difference between two portions. Conclusion. The Empty-can exercise requires more strength of the middle deltoid, subscapularis and supraspinatus to keep the arm in internal rotation. The increased activity of the middle deltoid and subscapularis muscles after the empty-can exercise can make the empty-can test less specific to the supraspinatus muscle. The empty-can test can induce pain and weakness due to the subscapularis pathology. The full-can test can be used to test the function of the supraspinatus with the least amount of surrounding middle deltoid and subacapularis muslce activity

INTRODUCTION. Rotator cuff tears are common injuries which often require surgical repair. Unfortunately, repairs often fail [1] and improved repair strength is essential. P2 Porous titanium (DJO Surgical, Austin TX) has been shown to promote osseointegration [2,3] and subdermal integration [4]. However, the ability of P2Porous titanium to aid in supraspinatus tendon-to-bone repair has not been evaluated. Therefore, the purpose of this study was to investigate P2 implants used to augment supraspinatus tendon-to-bone repair in a rat model [5]. We hypothesized that supraspinatus tendon-to-bone repairs with P2 implants would allow for ingrowth and increased repair strength when compared to standard repair alone. METHODS. Thirty-four adult male Sprague-Dawley rats were used (IACUC approved). Rats received bilateral supraspinatus detachment and repair with one limb receiving P2 implant. Animals were sacrificed at time 0 (n=3), 2 weeks (n=8), 4 weeks (n=9) and 12 weeks (n=14). Limbs were either dissected for histological and SEM analysis or mechanical testing as described previously [5]. Specimens for histology and SEM were embedded in PMMA for tissue-implant interface analysis. Specimens were first viewed in SEM under BSE to detect bony ingrowth, then stained with Sanderson's Rapid Bone Stain and viewed under transmitted and polarized light for tissue ingrowth. Comparisons were made using Student's t-tests with significance at p≤0.05. RESULTS. No differences in cross-sectional area were detected at any time point (Fig 1A). Percent relaxation was significantly increased in the P2 group at 2 weeks, but not at 4 and 12 weeks (Fig 1B). Maximum load was significantly increased in the P2 group at 2 weeks, but not at 4 weeks (Fig 1C – maximum load not reported due to failure at grip at 12 weeks). Modulus was significantly increased in the P2 group at 4 weeks, but not at 2 or 12 weeks (Fig 1D). No differences were detected in stiffness at any time point (data not shown). BSE analysis demonstrated bone ingrowth (Fig 2) and histological analysis showed soft tissue integration (Fig 3). DISCUSSION. Results indicate superior mechanical properties in the P2 group at 2 and 4 weeks, and tissue ingrowth at all time points. Importantly, at 2 weeks, the P2group had 76% increased maximum load compared to standard repair. As supraspinatus tendon re-tears are extremely common early [1] and occur at the tendon-to-bone interface, this finding supports the reduction of re-tear risk with the P2 implant. Although no differences were detected in maximum load at 4 weeks, the increase at 2 weeks denotes that P2 implants improved early tendon-to-bone healing. Additionally, at 4 weeks, the P2 implant group had significantly increased elastic modulus, further supporting increased mechanical properties due to the P2 implant. Clinically, improved early healing might allow faster rehabilitation and associated recovery. This study demonstrates that the P2 implant improves tendon-to-bone healing up to 4 weeks (with no detrimental effects at longer time points), suggesting that P2 porous titanium may be of benefit for use in clinical rotator cuff repairs

The purpose of this study was to clarify the effect of delay of the reattachment of the supraspinatus tendon into a bony trough to the strength of the repaired tendon-bone complex. The supraspinatus tendon of rabbits were transected and reattached into bony troughs at the greater tuberosity immediately and six weeks after transection. The tensile strength of the tendon-bone complex, harvested twelve weeks after reattachment, were measured. The tensile strength showed no difference between immediate and delayed reattached shoulders. Six weeks delay of supraspinatus tendon repair seems not to weaken the tensile strength of repaired tendon-bone complex. The purpose of this study was to clarify the effect of timing of surgery on the strength of the supraspinatus tendon-bone complex after the reimplantation of the tendon into a bony trough. In eight rabbits, the supraspinatus tendon was transected and reinserted into a bony trough at the greater tuberosity (early reattachment group). In seven rabbits, the supraspinatus tendon was reinserted six weeks after transection (delayed reattachment group). In both groups, the rabbits were sacrificed twelve weeks after reattachment, and the tensile strength of the tendon-bone complex was measured. The contralateral shoulders served as controls. None of the operated tendons failed at the site of reimplantation. The ratio of tensile strength of the operated tendon-bone complex to the controls showed no difference between two groups (Immediate reattachment group: 79.9± 1 S.E. 16.5%, delayed reattachment group: 80.4± 12.6%, P> 0.05). This is the first experimental study to compare the tensile strength of supraspinatus tendon-bone complex repaired after different time intervals. Stress-shielded tendon & bone tend to decrease their tensile strength. Given the six weeks duration of detachment, a weaker tensile strength of delayed reattachment group was expected than of the early reattachment group. The fact that both groups did not show a difference might be due to the recovery of tensile strength of tendon & bone in twelve weeks after reattachment. Six weeks delay of repair of supraspinatus tendon does not weaken the tensile strength of repaired tendon-bone complex. Fundings This study has been supported in part by a grant from the American Shoulder and Elbow Surgeons

Purpose of the study: Compression of the suprascapular nerve in the superior or inferior scapular incisures is a well-known syndrome compression syndrome triggered in the narrow osteofibrous tunnel. This study was undertaken after observing several cases of nerve compression in the supraspinatus fossa after neruolysis procedures. We wanted to better understand the relations with the supraspinatus fascia. Material and methods: Thirty human cadaver shoulders were dissected. After exposing the supra and infraspina-tus fossae and section of the scapular spine, the supra and infraspintus tendons were sectioned and folded back medially to expose the suprascapular pedicle in the superior scapular incisure, the supraspinatus fossa, and the inferior scapular incisure. The presence of a fascia sheathing the nerve, of subfascial tissue, and of a transversal inferior (spinoglenoid) ligament was noted together with the histology of the observed structures. Results: A supraspinatus fascia sheathing the nerve was observed in 29 dissections. This fascia was inserted on the superior border of the scapula and the superior scapular ligament and the floor of the supraspinatus fossa. Diffuse adipose deposits under the fascia was observed in 55.5% of the dissections, or located around the vasculonervous bundle in 44.5%. There was a fibrous buttonhole facing the lateral border of the spine in 28 shoulders with a thickened zone which constituted histologically the equivalent of an inferior transvers ligament in 26 shoulders. One subfascial lipoma was discovered. Discussion: Sheathing with a supraspinatus fascia could explain suprascapular nerve compression in the supra-spinatus fossa where the nerve is exposed to compression against the bony base on which it runs between the superior and inferior incisures. These anatomic data suggest that suprascapular neurolysis should release the nerve over its entire length and not just at the superior or inferior scapular incisure. Conclusion: The succession of the superior transverse ligament, the supraspinatus fascia, and the inferior transverse ligament constitutes an osteofibrous tunnel which should be considered as a potential source of a suprascapular tunnel syndrome at three levels

Aim: The purpose of this study was to evaluate the cytokine molecules present in a rat tendinopathy model and in the torn edge of human rotator cuff tendon in an attempt to understand their role in tendon degeneration. Methods: A rat tendon overuse model was used with custom microarrays consisting of 5760 rat oligonucleotide features in duplicate. Seventeen torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from patients undergoing arthroscopic shoulder surgery.Control samples of subscapularis tendon were collected from ten patients undergoing arthroscopic stabilisation surgery.Specimens were analysed for the presence of interleukins 18, 15, 12, 11, 6, 2, macrophage inhibitory factor (MIF), and tumour necrosis factor ƒÑ by semiquantitative RT-PCR and immunohistochemistry. Tendinopathy was assessed on a basic histological scale. Results: Rat Microarray analysis: Upregulation of IL-6, IL-11 and IL18 receptor was noted in the degenerated rat supraspinatus tendon. Downregulation of IL-2 was noted. No other cytokine signal was expressed. Histological analysis: All torn human supraspinatus tendons changes consistent with marked tendinopathy. Matched subscapularis tendon showed appearances of moderate-advanced degenerative change. Cytokine mRNA expression: TNF-£\ mRNA expression was found to be significantly elevated (p< 0.01) in subscapularis tendon compared to torn supraspinatus samples. The expression levels of IL-18, IL-15, IL-6 and MIF was significantly higher in the torn edges of supraspinatus when compared to matched subscapularis tendon and normal control tendon (p< 0.001). Immunohistochemical analysis: Presence of IL-18, IL-15, Il-6, MIF and TNF-£\ was confirmed in all samples of torn supraspinatus tendon. Significantly increased levels of IL-18, IL-15, IL-6 and MIF were found in torn supraspinatus. (p< 0.01) compared to matched and normal subscapularis. Conclusions: Cytokines have been shown to promote the intensive production of reactive O2 metabolites . 1. and are potent agonists of protein kinases . 2. Our finding of significantly increased cytokine levels may suggest that these molecules when expressed during the degenerate and healing phases of tendon injury result in the subsequent production of reactive O2 species and protein kinases. 3. causing tendon damage or failure of the normal reparative process. Our finding of marked tendinopathy in matched subscapularis tendon may also provide a useful human tendinopathy model