The relationship between the duration and the retraction and atrophy grades in traumatic isolated full-thickness supraspinatus tears in young patients.

BACKGROUND: The study aimed to determine the grade of retraction and atrophy according to the time elapsed in traumatic isolated full-thickness supraspinatus (SS) tears in young patients. METHODS: One thousand twenty-six patients, who underwent arthroscopic shoulder surgery, were retrospectively reviewed. Pre-operative magnetic resonance imaging (MRI) of 69 patients aged 18 to 40 years with isolated traumatic full-thickness SS lesions remaining after exclusion criteria were evaluated for tendon retraction and atrophy grades. SS retraction was determined from a T2-weighted oblique coronal MRI slice, and the atrophy grade was determined from the T1-weighted oblique sagittal MRI slice. The patients were divided into four groups 0-1 month, 1-3 months, 3-6 months, and 6-12 months according to the time between trauma and MRI. The relationship of tendon retraction and muscle atrophy with elapsed time was evaluated, in addition, comparisons between groups were made. RESULTS: Thirty-one (45%) of the patients were female and their mean age was 30 ± 7.3 (18-40) years. The mean age of men was 30.5 ± 6.9 (18-39) years (p = 0.880). The time between rupture and MRI was moderately correlated with retraction and strongly correlated with atrophy grades (r = 0.599, 0.751, respectively). It was observed that there was a statistically significant difference between the 1st (0-1 month) and 2nd (1-3 months) groups (p = 0.003, 0.001, respectively), and between the 2nd and 3rd (3-6 months) groups (p = 0.032, 0.002, respectively), but there was no significant difference between the 3rd and 4th (6-12 months) groups (p = 0.118, 0.057, respectively). In addition, there was a moderate correlation between tendon retraction and atrophy grades (r = 0.668). Power (1- b) in post hoc analysis was calculated as 0.826. CONCLUSIONS: The current study, supported by arthroscopy, showed that there is a moderate and strong positive correlation between the time elapsed after trauma and the level of retraction and degree of atrophy in traumatic full-thickness SS tears, and demonstrated the importance of early surgical intervention in young patients.

The Biological Effect of Platelet-Rich Plasma on Rotator Cuff Tears: A Prospective Randomized In Vivo Study.

The positive effect of platelet-rich plasma (PRP) on tendon metabolism has been extensively investigated and proven in vitro. Additionally, in vivo animal studies have correlated the application of PRP with the enhancement of tenocyte anabolic activity in the setting of tendon degeneration. However, less is known about its in vivo effect on human tendon biology. The purpose of the current prospective randomized comparative study was to evaluate the effect of PRP on torn human supraspinatus tendon. Twenty consecutive eligible patients with painful and magnetic resonance imaging (MRI)-confirmed degenerative supraspinatus tendon tears were randomized in a one-to-one ratio into two groups. The patients in the experimental group (n = 10) underwent an ultrasound-guided autologous PRP injection in the subacromial space 6 weeks before the scheduled operation. In the control group (n = 10), no injection was made prior to surgery. Supraspinatus tendon specimens were harvested from the lateral end of the torn tendon during shoulder arthroscopy and were evaluated under optical and electron microscopy. In the control group, a mixed cell population of oval and rounded tenocytes within disorganized collagen and sites of accumulated inflammatory cells was detected. In contrast, the experimental group yielded abundant oval-shaped cells with multiple cytoplasmic processes within mainly parallel collagen fibers and less marked inflammation, simulating the intact tendon structure. These findings indicate that PRP can induce microscopic changes in the ruptured tendon by stimulating the healing process and can facilitate a more effective recovery.

Biomechanical effects of deltoid muscle atrophy on rotator cuff tissue: a finite element study.

The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

Effect of magnetic microbeads on sustained and targeted delivery of transforming growth factor-beta-1 for rotator cuff healing in a rat rotator cuff repair model.

Structural failure is a well-established complication of rotator cuff repair procedures. To evaluate the effect of magnetic microbeads, designed for precise drug delivery via magnetic force, on sustained transforming growth factor-beta-1 (TGF-ß1) release and rotator cuff healing in a rat rotator cuff repair model. TGF-ß1 laden microbeads were prepared, and baseline in vitro experiments included the magnetization of the microbeads and TGF-ß1 release tests. In an in vivo experiment using a rat rotator cuff repair model on both shoulders, 72 rats were randomly assigned to three groups (24 per group): group A, conventional repair; group B, repair with and simple TGF-ß1 injection; and group C, repair with magnet insertion into the humeral head and TGF-ß1 laden microbead injection. Delivery of TGF-ß1 was evaluated at 1 and 7 days after the intervention using PCR, Western blot, and immunohistochemistry. At 6 weeks post-intervention, rotator cuff healing was assessed using biomechanical and histological analysis. The in vitro experiments confirmed the magnetization property of the microbeads and sustained delivery of TGF-ß1 for up to 10 days. No difference in the TGF-ß1 expression was found at day 1 in vivo. However, at day 7, group C exhibited a significantly elevated expression of TGF-ß1 in both PCR and Western blot analyses compared to groups A and B (all P < 0.05). Immunohistochemical analysis revealed a higher expression of TGF-ß1 at the repair site in group C on day 7. At 6 weeks, biomechanical analysis demonstrated a significantly higher ultimate failure load in group C than in groups A and B (P < 0.05) and greater stiffness than in group A (P = 0.045). In addition, histological analysis showed denser and more regular collagen fibers with complete continuity to the bone in group C than in groups A and B, a statistically significant difference according to the semi-quantitative scoring system (all P < 0.05). The use of the TGF-ß1 laden magnetic microbeads demonstrated sustained delivery of TGF-ß1 to the repair site, improving rotator cuff healing.

Association of calcific rotator cuff tendinopathy with nephrolithiasis and/or cholelithiasis: A case-control study.

This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (P < .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (P = .006) and 16 (13.9%) (P = .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, P = .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, P = .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with P < .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, P = .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis.

The effects of tears in infraspinatus on other rotator cuff constituents.

The rotator cuff tear effects on glenohumeral joint tissues, such as superior labrum anterior-posterior (SLAP) lesions, have been studied experimentally or numerically in various cases. In relation to these studies, and as a novel feature of our study, infraspinatus (INF) muscle tear effects on other muscle force variations and stress and strain increases on glenoid labrum (GL), glenoid cartilage (GC) tissues, and a SLAP pathology were investigated. The ITK-SNAP Software (ISS) was used to segment the humerus and glenoid bone. The surface entities were segmented and exported to SolidWorks 2019, where the finite element model (FEM) was completed. Static optimizations of the muscle forces were calculated using a generic model in OpenSim 4.1 for the 0-3.88 s time interval to perform our finite element analyses (FEAs) in ANSYS 19.3 for the intact, partial torn, and fully torn INF muscle. The FEAs were also conducted for the specified time interval. The stress and strain increases on the GL, and GC tissues were determined to be critical when compared with yield strengths. In the case of fully torn INF, the GL and cartilage interfacial principal stress was calculated to be 3.3856 MPa. In the case of the fully torn INF, the principal stress that occurred on the GC tissue was calculated to be 42.465 MPa. In the case of the intact INF, the principal stress that occurred on the labrum was obtained as 4.257 MPa. These results showed that there was no detachment or disorder on the designated tissues caused by the INF muscle tear when the shoulder functioned at 60° of external rotation at 11° of abduction. Nonetheless, a minor amount of external force could cause severe pathological effects on the specified tissues.

Platelet-rich plasma in the management of rotator cuff tendinopathy.

Platelet-rich plasma (PRP) is an autologous blood-derived product that has gained significant attention in the treatment of tendinopathies as one of many treatment modalities in the field of regenerative medicine. Rotator cuff pathologies are the leading cause of shoulder pain. Despite the high success rate with conservative treatment and arthroscopic surgical repair, the search for a nonsurgical treatment has made PRP a trending topic recently. The purpose of this article is to review the recent literature data on the possible role of PRP in different rotator cuff pathologies. The limited data in the literature about isolated tendinopathies without a tear (tendonitis and tendinosis) suggests potential benefit from conservative treatment with PRP. Many studies exist for the treatment of rotator cuff tears solely using PRP or as an augmentation to arthroscopic repair. Despite the large number of randomized clinical trials and meta-analyses about the topic, there is no consensus in favor of routine application of PRP in this patient population. The existing reliable evidence of benefit seems to be restricted to its use in only inflammatory tendinopathies with preserved tendon integrity.

Rotator Cuff Tendinopathy: Pathways of Apoptosis.

Rotator cuff repair is usually successful, but retear is not uncommon. It has been previously identified that there is a higher incidence of apoptosis in the edges of the torn supraspinatus tendon. A prospective cohort study was conducted with 28 patients-14 rotator cuff tear patients, 5 instability patients, and 9 Anterior cruciate ligament reconstruction patients to determine whether there was any increase in several genes implicated in apoptosis, including Fas receptor (FasR), Fas ligand, Aifm-1, Bcl-2, Fadd, Bax, and caspase-3. There was a significant expression of Bax (P=0.2) and FasR (P=0.005) in the edges of torn supraspinatus tendons, and in intact subscapularis tendons, there was a significant expression of caspase-3 (P=0.02) compared with samples from the torn supraspinatus tendon (P=0.04). The cytochrome c pathway, with its subsequent activation of caspase-3, as well as the TRAIL-receptor signaling pathway involving FasR have both been implicated. The elevated expression of Bax supported the model that the Bax to Bcl-2 expression ratio represents a cell death switch. The elevated expression of Bax in the intact subscapularis tissue from rotator cuff tear patients also may confirm that tendinopathy is an ongoing molecular process.

Transcriptomics reveals dynamic changes in the "gene profiles" of rat supraspinatus tendon at three different time points after diabetes induction.

OBJECTIVE: There is increasing evidence that type 2 diabetes mellitus (T2DM) is an independent risk factor for the occur of tendinopathy. Therefore, this study is the first to explore the dynamic changes of the "gene profile" of supraspinatus tendon in rats at different time points after T2DM induction through transcriptomics, providing potential molecular markers for exploring the pathogenesis of diabetic tendinopathy. METHODS: A total of 40 Sprague-Dawley rats were randomly divided into normal (NG, n = 10) and T2DM groups (T2DM, n = 30) and subdivided into three groups according to the duration of diabetes: T2DM-4w, T2DM-8w, and T2DM-12w groups; the duration was calculated from the time point of T2DM rat model establishment. The three comparison groups were set up in this study, T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG. Differentially expressed genes (DEGs) in 3 comparison groups were screened. The intersection of the three comparison groups' DEGs was defined as key genes that changed consistently in the supraspinatus tendon after diabetes induction. Cluster analysis, gene ontology (GO) functional annotation analysis and Kyoto encyclopedia of genes and genomes (KEGG) functional annotation and enrichment analysis were performed for DEGs. RESULTS: T2DM-4w group vs. NG, T2DM-8w group vs. NG, and T2DM-12w group vs. NG detected 519 (251 up-regulated and 268 down-regulated), 459 (342 up-regulated and 117 down-regulated) and 328 (255 up-regulated and 73 down-regulated) DEGs, respectively. 103 key genes of sustained changes in the supraspinatus tendon following induction of diabetes, which are the first identified biomarkers of the supraspinatus tendon as it progresses through the course of diabetes.The GO analysis results showed that the most significant enrichment in biological processes was calcium ion transmembrane import into cytosol (3 DEGs). The most significant enrichment in cellular component was extracellular matrix (9 DEGs). The most significant enrichment in molecular function was glutamate-gated calcium ion channel activity (3 DEGs). The results of KEGG pathway enrichment analysis showed that there were 17 major pathways (p < 0.05) that diabetes affected supratinusculus tendinopathy, including cAMP signaling pathway and Calcium signaling pathway. CONCLUSIONS: Transcriptomics reveals dynamic changes in the"gene profiles"of rat supraspinatus tendon at three different time points after diabetes induction. The 103 DEGs identified in this study may provide potential molecular markers for exploring the pathogenesis of diabetic tendinopathy, and the 17 major pathways enriched in KEGG may provide new ideas for exploring the pathogenesis of diabetic tendinopathy.

Histological and biochemical changes in a rat rotator cuff tear model with or without the subacromial bursa.

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1ß (IL-1ß), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained.

Lineage tracing reveals a novel PDGFRß+ satellite cell subset that contributes to myo-regeneration of chronically injured rotator cuff muscle.

Massive rotator cuff (RC) tendon tears are associated with progressive fibro-adipogenesis and muscle atrophy that altogether cause shoulder muscle wasting. Platelet derived growth factor ß (PDGFRß) lineage cells, that co-express PDGFRα have previously been shown to directly contribute to scar formation and fat accumulation in a mouse model of irreversible tendon and nerve transection (TTDN). Conversely, PDGFRß+ lineage cells have also been  shown to be myogenic in cultures and in other models of skeletal muscle injury. We therefore hypothesized that PDGFRß demarcates two distinct RC residing subpopulations, fibro-adipogenic and myogenic, and aimed to elucidate the identity of the PDGFRß myogenic precursors and evaluate their contribution, if any, to RC myo-regeneration. Lineage tracing revealed increasing contribution of PDGFRß+ myo-progenitors to the formation of GFP+ myofibers, which were the most abundant myofiber type in regenerated muscle at 2 weeks post-TTDN. Muscle regeneration preceded muscle atrophy and both advanced from the lateral site of tendon transection to the farthest medial region. GFP+/PDGFRß+Sca-1-lin-CXCR4+Integrin-ß1+ marked a novel subset of satellite cells with confirmed myogenic properties. Further studies are warranted to identify the existence of PDGFRß+ satellite cells in human and other mouse muscles and to define their myo-regenerative potential following acute and chronic muscle injury.

The subacromial bursa modulates tendon healing after rotator cuff injury in rats.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa's effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6. These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

Fixation technique of biodegradable magnesium alloy suture anchor in the rotator cuff repair of the shoulder in a goat model: a technical note.

BACKGROUND: Shoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model. METHODS: We developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration. RESULTS: The 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels. CONCLUSIONS: The findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery.

Semi-Bone Tunnel Technique Using Double-Row Suture Bridge Combined With Platelet-Rich Plasma Hydrogel for Rotator Cuff Repair in a Rabbit Model.

BACKGROUND: The approach to managing the footprint area and reconstructing the tendon-bone interface (TBI) is critical for optimal healing. PURPOSE: To evaluate the outcomes of the semi-bone tunnel (SBT) technique using a double-row suture bridge combined with platelet-rich plasma (PRP) hydrogel for rotator cuff repair in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 New Zealand White rabbits were divided into 4 groups. The supraspinatus tendons were severed at the footprint to create a rotator cuff tear model in the surgical groups. Rabbits were treated with the traditional onto-surface repair (control group), SBT technique (SBT group), and SBT technique combined with PRP hydrogel implantation (SBT+PRP group). The rabbits without surgery were the normal group. At 8 weeks after surgery, macroscopic observation, magnetic resonance imaging (MRI) and micro-computed tomography (µCT) examinations, histological evaluations, and biomechanical tests were performed to assess the curative effects of the given treatments. RESULTS: The MRI results showed that the repaired supraspinatus tendon presented a uniform signal, minimal inflammatory response, and the lowest signal-to-noise quotient value in the SBT+PRP group. The µCT results suggested that the SBT technique did not reduce the local bone mineral density in the TBI area compared with the onto-surface repair technique. The histological staining results showed that the regenerated TBI in the SBT+PRP group had a 4-layer structure similar to the natural tissue. The highest values for biomechanical properties were observed in the SBT+PRP group, and there was no significant difference between the SBT+PRP group and normal group. CONCLUSION: The SBT technique presented a better tendon-bone healing effect for rotator cuff tear in the rabbit model compared with the traditional onto-surface repair technique. The specimens in the SBT+PRP group had a similar TBI structure and biomechanical properties to the natural tissue. CLINICAL RELEVANCE: The SBT technique can be an alternative surgical approach for rotator cuff repair, especially for moderate to large tears and cases requiring scaffold implantation.

The association between a rotator cuff tendon tear and a tear of the long head of the biceps tendon: Chart review study.

Rotator cuff (RC) and long head of the biceps tendon (LHBT) tears are common shoulder problems presented to the orthopedic clinic. The aim of this study was to assess the association between RC and LHBT tears among a Saudi population sample. A total of 243 patients who were diagnosed with shoulder pain due to RC or LHBT tear between 2016 and 2018 using a magnetic resonance imaging scan were included in this study. Females comprised 66% of the sample, and 59% (n = 143) of the shoulders were on the right side. The mean age of the patients was 58 ± 11 years, ranging from 23 to 88 years. A significant association was detected between the LHBT and RC tears (P < 0.001). Out of 26 cases showing RC and LHBT tears, 81% had a full thickness tear, whereas 19% had a partial tear. The LHBT tears were presented significantly in 48% of cases with at least two completely torn RC compared to 10% in cases with one completely torn RC (P < 0.001). The LHBT tear was significantly observed in shoulders with RC tears including the tendons of subscapularis, supraspinatus, and infraspinatus, but not the teres minor (P < 0.001). Both types of tears were presented significantly in senior patients aged more than 65 years compared to younger patients (P < 0.01). Thus, the LHBT should be assessed carefully in shoulders with more than one RC tear or in chronic cases.

Healthy Tendon Stem Cell-Derived Exosomes Promote Tendon-To-Bone Healing of Aged Chronic Rotator Cuff Tears by Breaking the Positive-Feedback Cross-Talk between Senescent Tendon Stem Cells and Macrophages through the Modulation of Macrophage Polarization.

The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.

Role of tear size and tendon degeneration for development of pain in rat models of rotator cuff tear.

BACKGROUND: Rotator cuff tear (RCT) is a frequent etiology of shoulder pain and disability; however, the triggers for the onset and aggravation of pain remain obscure. In this study, we established novel rat RCT models to examine the impact of tear size and tendon degeneration on pain. METHODS: Fifty-five adult male Sprague-Dawley rats were allocated into 4 study groups: large tear (L group, n = 10), small tear (S group, n = 15), small tear with scratching (S+ group n = 15), and sham surgery (Sham group, n = 15). Pain-related behaviors were evaluated by weight distribution of forelimbs during a 5-minute free gait using a dynamic weight-bearing apparatus at 2, 4, 6, and 8 weeks. Calcitonin gene-related peptide (CGRP) expressions in ipsilateral dorsal root ganglion (DRG) neurons of C4, C5, and C6 were evaluated at 4 and 8 weeks. The area of scar tissues around the torn tendon, infiltration of inflammatory cells, and severity of tendon degeneration (modified Bonar score) were histologically assessed at 4 and 8 weeks. Additionally, enzyme-linked immunosorbent assay (ELISA) was conducted to evaluate the levels of cyclooxygenase-2 (COX-2) and nerve growth factor (NGF) expression in torn tendons and surrounding tissues at 4 weeks. RESULTS: The weight distribution ratio (ipsilateral and contralateral side) was significantly decreased in the L and S+ group compared with its baseline and Sham group (P < .05), but the S group showed no significant difference compared with the Sham. The ratio of CGRP-immunoreactive neurons in the DRGs was significantly higher in the L and S+ groups than in the S and Sham groups. The histologic assessment indicated that scar tissue formation was more extensive in the L group than in the S and S+ groups. Still, there was no significant difference between the S and S+ groups. The modified Bonar score was considerably higher in the S+ group than in the S group. Furthermore, ELISA analysis demonstrated no significant disparity in COX-2 levels between the groups; however, NGF levels were substantially higher in the S+ group than in the S and Sham groups. CONCLUSION: The present study provides compelling evidence that large RCT is strongly associated with heightened pain severity in a rat model. Nevertheless, even a small tear can significantly aggravate pain when the torn tendon is degenerated. CGRP upregulation driven by peripheral NGF possibly played a pivotal role in the genesis and exacerbation of pain in small RCT.

The Relationship Among Probable SARCopenia, Osteoporosis and SuprasPinatus Tendon Tears in Postmenopausal Women: The SARCOSP Study.

We aimed to investigate the relationship among probable sarcopenia, osteoporosis (OP) and supraspinatus tendon (SSP) tears in postmenopausal women. Postmenopausal women screened/followed for OP were recruited. Demographic data, comorbidities, exercise/smoking status, and handgrip strength values were recorded. Probable sarcopenia was diagnosed as handgrip strength values < 20 kg. Achilles and SSP thicknesses were measured using ultrasound. Among 1443 postmenopausal women, 268 (18.6%) subjects had SSP tears. Unilateral tears were on the dominant side in 146 (10.1%) and on the non-dominant side in 55 women (3.8%). In contrast to those without, women with SSP tears had older age, lower level of education, thinner SSP and lower grip strength (all p < 0.05). In addition, they had higher frequencies of hypertension, hyperlipidemia, DM, OP and probable sarcopenia, but lower exercise frequency (all p < 0.05). Binary logistic regression modeling revealed that age [odds ratio (OR): 1.046 (1.024-1.067 95% CI)], hypertension [OR: 1.560 (1.145-2.124 95% CI)], OP [OR: 1.371 (1.022-1.839 95% CI)] and probable sarcopenia [OR: 1.386 (1.031-1.861 95% CI)] were significant predictors for SSP tears (all p < 0.05). This study showed that age, presence of hypertension, probable sarcopenia and OP were related with SSP tears in postmenopausal women. To this end, although OP appeared to be related to SSP tears, SSP tear/thickness evaluation can be recommended for OP patients, especially those who have other risk factors such as older age, higher BMI, hypertension, and probable sarcopenia.

Teres minor denervation and pathologies resulting in shoulder joint instability and rotator cuff tears: A retrospective cross-sectional MRI study.

Teres minor denervation (TMD) has gained increasing attention in recent years, particularly with the advent of magnetic resonance imaging (MRI). The potential association between TMD and shoulder instability or rotator cuff tear remains a subject of interest in the orthopedic community. In this retrospective and cross-sectional study, authors aim to investigate the potential association between TMD and shoulder instability or rotator cuff tears. Authors retrospectively analyzed MRI findings from 105 patients with TMD, focusing on rotator cuff pathologies, posterior labrocapsular complex (PLCC) tears, and posteroinferior glenohumeral joint capsule alterations. Authors assessed the association between TMD and rotator cuff and PLCC tears. For the multivariate analysis, partial proportional odds models were constructed for subscapularis (SSC) and SSP tears. Rotator cuff tears were present in 82.9% of subjects, with subscapularis (SSC) tears being the most frequent (77.1%). A significant association was observed between TMD and rotator cuff pathology (P = .002). PLCC tears were found in 82.3% of patients, and humeral position relative to the osseous glenoid was noted in 60% of patients with TMD. A significant association was identified between TMD and shoulder instability or labral/capsular abnormalities (P < .001). More than half of the cases exhibited a long tethering appearance toward the axillary neurovascular bundle on T1-weighted sagittal images. Our findings suggest that TMD is significantly associated with rotator cuff tears and shoulder instability. This study highlights the importance of identifying and treating PLCC tears in patients with TMD to address shoulder instability. Further research is needed to elucidate the role of TMD in the pathogenesis of shoulder instability and rotator cuff pathology.

Differences in Clinical Outcomes Between Patients With Retear After Supraspinatus Tendon Repair and Those With Intact Repair at 5-Year Follow-up.

BACKGROUND: It is well known that rotator cuff repair is associated with an overall retear rate of 21% to 26%. However, a cuff retear may not necessarily be associated with poor clinical outcomes. HYPOTHESIS: There would be no difference in clinical outcomes between patients with a cuff retear and those with an intact repair at a midterm follow-up of 5 years. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective study was conducted involving patients who received arthroscopic complete repair of the supraspinatus tendon between January 2009 and December 2017. Patients who did not have a postoperative magnetic resonance imaging (MRI) scan or who had a follow-up of <5 years were excluded. Clinical outcomes, including the visual analog scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and active forward flexion (FF) of the involved shoulder were assessed at the 2-year and 5-year follow-up points. RESULTS: The study group included 105 patients with a mean follow-up of 85 months. MRI scans were performed at a mean of 20 months. Fourteen full-thickness cuff retears and 91 intact repairs were identified using postoperative MRI scans. Significant improvement in VAS score, ASES score, and FF were found between the preoperative assessment and the 2 designated follow-up points (2 years and 5 years) in both the cuff retear and the intact repair groups (P < .001). The VAS and ASES scores at the 2-year follow-up for the intact repair group were 1.8 ± 2.0 and 80.7 ± 18.1, respectively. The corresponding values for the retear group were 2.3 ± 2.2 and 71.9 ± 19.5, respectively. No significant difference was found between the 2 groups in the VAS and ASES scores at the 2-year follow-up. However, patients with an intact repair had a better VAS score (1.4 ± 1.8; P = .049) and ASES score (81.7 ± 17; P = .019) than those with a cuff retear at the 5-year assessment (3.0 ± 2.8 and 67.1 ± 22.9, respectively). In the intact repair group, 91% of patients achieved the minimal clinically important difference for the 5-year VAS score, compared with 54% in the cuff retear group (P < .001). The corresponding values for the 5-year ASES score were 80% and 54%, respectively (P = .044). FF measurements at the 5-year follow-up in patients with intact repair and those with a cuff retear were 161°± 23° and 144°± 37°, respectively (P = .059). Continuous improvement in VAS score and FF between the 2-year and 5-year follow-up was observed in the intact repair group (P = .005 and P = .04, respectively). CONCLUSION: The patients with an intact repair had better VAS and ASES scores compared with those who had a cuff retear at a midterm follow-up of 5 years. Between the 2-year and the 5-year follow-up, some further improvement was observed in the VAS score and FF in the intact repair group.