Socioeconomic Status and Time to Treatment in Patients With Traumatic Rotator Cuff Tears.

INTRODUCTION: Socioeconomic status (SES) affects access to care for traumatic rotator cuff (RTC) tears. Delayed time to treatment (TTT) of traumatic RTC tears results in worse functional outcomes. We investigated disparities in TTT and hypothesized that individuals from areas of low SES would have longer time to surgical repair. METHODS: Patients who underwent repair of a traumatic RTC tear were retrospectively reviewed. Median household income and Social Deprivation Index were used as a proxy for SES. The primary outcome was TTT. Patients were further stratified by preoperative forward flexion and number of tendons torn. RESULTS: A total of 221 patients met inclusion criteria. No significant difference in TTT was observed between income classes (P = 0.222) or Social Deprivation Index quartiles (P = 0.785). Further stratification by preoperative forward flexion and number of tendons torn also yielded no significant difference in TTT. DISCUSSION: Contrary to delays in orthopaedic care documented in literature, our study yielded no difference in TTT between varying levels of SES, even when stratified by the severity of injury. Thus, we reject our original hypothesis. Based on our findings, mechanisms in place at our institution may have mitigated some of these health disparities within our community.

Partial-Thickness Rotator Cuff Tears: Current Concepts.

¼ Partial-thickness rotator cuff tears (PTRCTs) are a common pathology with a likely high asymptomatic incidence rate, particularly in the overhead athlete.¼ The anatomy, 5-layer histology, and relationship to Ellman's classification of PTRCTs have been well studied, with recent interest in radiographic predictors such as the critical shoulder angle and acromial index.¼ Depending on the definition of tear progression, rates of PTRCT progression range from 4% to 44% and appear related to symptomatology and work/activity level.¼ Nearly all PTRCTs should be managed conservatively initially, particularly in overhead athletes, with those that fail nonoperative management undergoing arthroscopic debridement ± acromioplasty if <50% thickness or arthroscopic conversion repair or in situ repair if >50% thickness.¼ Augmentation of PTRCTs is promising, with leukocyte-poor platelet-rich plasma having the most robust body of supportive data. Mesenchymal signaling cell biologics and the variety of scaffold onlay augments require more rigorous studies before regular usage.

Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing.

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.

Paracrine signals influence patterns of fibrocartilage differentiation in a lyophilized gelatin hydrogel for applications in rotator cuff repair.

Rotator cuff injuries present a clinical challenge for repair due to current limitations in functional regeneration of the native tendon-to-bone enthesis. A biomaterial that can regionally instruct unique tissue-specific phenotypes offers potential to promote enthesis repair. We have recently demonstrated the mechanical benefits of a stratified triphasic biomaterial made up of tendon- and bone-mimetic collagen scaffold compartments connected via a continuous hydrogel, and we now explore the potential of a biologically favorable enthesis hydrogel for this application. Here we report in vitro behavior of human mesenchymal stem cells (hMSCs) within thiolated gelatin (Gel-SH) hydrogels in response to chondrogenic stimuli as well as paracrine signals derived from MSC-seeded bone and tendon scaffold compartments. Chondrogenic differentiation media promoted upregulation of cartilage and entheseal fibrocartilage matrix markers COL2, COLX, and ACAN as well as the enthesis-associated transcription factors SCX, SOX9, and RUNX2 in hMSCs within Gel-SH. Similar effects were observed in response to TGF-ß3 and BMP-4, enthesis-associated growth factors known to play a role in entheseal development and maintenance. Conditioned media generated by hMSCs seeded in tendon- and bone-mimetic collagen scaffolds influenced patterns of gene expression regarding enthesis-relevant growth factors, matrix markers, and tendon-to-bone transcription factors for hMSCs within the material. Together, these findings demonstrate that a Gel-SH hydrogel provides a permissive environment for enthesis tissue engineering and highlights the significance of cellular crosstalk between adjacent compartments within a spatially graded biomaterial.

The effects of telemedicine on Rotator cuff-related shoulder function and pain symptoms: a meta-analysis of randomized clinical trials.

BACKGROUND: The effectiveness of telemedicine in aiding rehabilitation exercises among patients with rotator cuff (RC) disorders remains unknown. Therefore, this meta-analysis aimed to assess the effectiveness of telemedicine in patients with RC disorders. METHODS: Randomized clinical trials (RCTs) on the effectiveness of telemedicine in patients with RC disorders were summarized through a meta-analysis. A systematic search for these RCTs was conducted in PubMed, Cochrane, Embase, and Web of Science databases up to July 2024. Statistical analysis was performed using Stata 16. Publication bias was estimated with the funnel plot and Egger's test. RESULTS: Ten studies involving 497 participants (telemedicine group = 248 and conventional group = 249) were enrolled, with follow-up durations ranging from 8 weeks to 48 weeks. Functional outcomes measured by the Constant-Murley score were markedly improved after treatment in the telemedicine group compared to the conventional group. Moreover, compared to conventional treatment, telemedicine significantly improved shoulder function evaluated by Quick Disabilities of the Arm, Shoulder, and Hand Score, relieved pain assessed by visual analog scale pain score, and improved range of motion after treatment and in the final follow-up period. CONCLUSION: Telemedicine has demonstrated potential in alleviating pain and enhancing shoulder function and motion in patients with RC injuries. It may be a feasible intervention for rehabilitation exercises. Further research with a large sample size and standardized treatment is warranted to validate these findings.

Effects of a web application based on multimedia animations to support therapeutic exercise for rotator cuff-related shoulder pain: protocol for an open-label randomised controlled trial.

INTRODUCTION: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder pain. Currently, exercise is proposed as the first-line treatment for patients suffering from RCRSP. However, adherence to therapeutic exercise programmes can be poor in the long term in a home setting. The aim of this study is to evaluate the effects of adding video animations to a traditional paper-based exercise programme. METHODS AND ANALYSIS: A single-centre, randomised, open-labelled clinical trial will be conducted in a hospital in Spain. Adults aged between 18 and 80 years diagnosed with RCRSP who meet the eligibility criteria will be included. Patients (n=132) will be randomised into two groups, with both receiving paper-based exercises, and the experimental group will also be provided with video animations. The participants will receive seven face-to-face physical therapy sessions and will be asked to perform the exercises at home for 6 months. The primary outcome measure will be the Shoulder Pain and Disability Index, measured at baseline, 3 weeks, 3 months (primary analysis) and 6 months. Secondary outcomes will be the patient's pain intensity during the last week (rest, during movement and at night); expectations of improvement; satisfaction with treatment; impression of improvement; perceived usability, usefulness and satisfaction of multimedia animations; and adherence to exercises. Generalised least squares regression models with an autoregressive-moving average lag one correlation structure will be implemented, with an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee of Hospital Universitario Fundación Alcorcón (Madrid, Spain), reference number CI18/16. All participants will sign an informed consent. The results will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05770908.

Comparative efficacy of platelet-rich plasma (PRP) injection versus PRP combined with vitamin C injection for partial-thickness rotator cuff tears: a randomized controlled trial.

BACKGROUND: The optimal approach for managing partial-thickness rotator cuff tears (PTRCT) remains controversial. Recent studies related to PTRCTs have shown that platelet-rich plasma (PRP) injection might be an effective treatment option. Despite the role of vitamin C in collagen synthesis and its antioxidant properties, the effects of combined PRP and vitamin C treatment on rotator cuff repair are not well understood. This study investigated the effect of combined treatment of PRP and vitamin C treatment on PTRCTs. METHODS: One hundred-ten patients with PTRCTs were randomly allocated to two groups and underwent subacromial injections of either (A) normal saline and platelet-rich plasma or (B) vitamin C and platelet-rich plasma. The Constant score, American Shoulder and Elbow Surgeons (ASES) score, and visual analog scale were used to evaluate the outcomes before, 1 month after, and 3 months after injection. RESULTS: At the 3-month follow-up, no statistically significant differences were observed between the two groups in terms of ASES and Constant scores. Although a slight difference favoring group B was noted in functional scores and pain reduction, this difference was not statistically significant. However, both groups demonstrated significant pain reduction over time (p-value < 0.001). Additionally, the enhancement of ASES and Constant scores in both groups was statistically significant (p-value < 0.001). CONCLUSIONS: In conclusion, both PRP injection alone and PRP combined with vitamin C led to significant reductions in pain and enhancements in function scores over time (p < 0.001), suggesting the effectiveness of PRP as a non-surgical treatment for PTRCTs within 3 months. While PRP alone showed significant benefits, further research is required to ascertain if the combination therapy offers statistically significant advantages over PRP alone. TRIAL REGISTRATION: Clinical trial registration code: IRCT20230821059205N1.

A New Tissue Engineering Strategy to Promote Tendon-bone Healing: Regulation of Osteogenic and Chondrogenic Differentiation of Tendon-derived Stem Cells.

In the field of sports medicine, repair surgery for anterior cruciate ligament (ACL) and rotator cuff (RC) injuries are remarkably common. Despite the availability of relatively effective treatment modalities, outcomes often fall short of expectations. This comprehensive review aims to thoroughly examine current strategies employed to promote tendon-bone healing and analyze pertinent preclinical and clinical research. Amidst ongoing investigations, tendon-derived stem cells (TDSCs), which have comparatively limited prior exploration, have garnered increasing attention in the context of tendon-bone healing, emerging as a promising cell type for regenerative therapies. This review article delves into the potential of combining TDSCs with tissue engineering methods, with ACL reconstruction as the main focus. It comprehensively reviews relevant research on ACL and RC healing to address the issues of graft healing and bone tunnel integration. To optimize tendon-bone healing outcomes, our emphasis lies in not only reconstructing the original microstructure of the tendon-bone interface but also achieving proper bone tunnel integration, encompassing both cartilage and bone formation. In this endeavor, we thoroughly analyze the transcriptional and molecular regulatory variables governing TDSCs differentiation, incorporating a retrospective analysis utilizing single-cell sequencing, with the aim of unearthing relevant signaling pathways and processes. By presenting a novel strategy rooted in TDSCs-driven osteogenic and chondrogenic differentiation for tendon-bone healing, this study paves the way for potential future research avenues and promising therapeutic applications. It is anticipated that the findings herein will contribute to advancing the field of tendon-bone healing and foster the exploration of TDSCs as a viable option for regenerative therapies in the future.

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.

Subacromial balloon spacer massive rotator cuff tear treatment systematic review and meta-analysis: Patient selection and physical therapy may be keys to outcome success.

PURPOSE: Subacromial balloon spacer implantation (SBSI) efficacy for massive rotator cuff tear treatment was evaluated based on perceived shoulder function, active shoulder mobility, pain, complications and research study methodological quality. The purpose was to better discern the efficacy of this device from both surgical and rehabilitative perspectives to improve patient outcomes. METHODS: PubMed, EMBASE and Cochrane Library databases were searched (1 January 2010 to 1 June 2024) using 'balloon spacer', 'subacromial spacer', 'subacromial balloon spacer', 'shoulder spacer' and 'inspace' terms. Pre-surgery (baseline), 12-month (12-m) and 24-month (24-m) post-SBSI mean changes were compared using one-way ANOVA and Scheffe post hoc tests, and comparative study effect sizes were calculated (p ≤ 0.05). RESULTS: This review consists of 27 studies with 894 patients (67.8 ± 5 years of age) and 29.4 ± 17-month follow-up. Modified Coleman Methodology Scores (MCMS) revealed fair overall quality (mean = 61.4 ± 11). Constant-Murley scores improved from 34.8 ± 6 (baseline), to 64.2 ± 9 (12-m) and 67.9 ± 8 (24-m) (12-m, 24-m > baseline, p < 0.001). ASES scores improved from 35.1 ± 14 (baseline), to 83.3 ± 7 (12-m) and 81.8 ± 5 (24-m)(12-m, 24-m > baseline, p < 0.001). VAS pain scores improved from 6.6 ± 1 (baseline), to 2.6 ± 1 (12-m) and 2.0 ± 1 (24-m) (12-m, 24-m < baseline, p < 0.001). Flexion increased from 108.5 ± 25° (baseline), to 128.5 ± 30° (12-m) and 151.2 ± 14° (24-m) (24-m > 12-m, baseline, p = 0.01). Abduction increased from 97.7 ± 24° (baseline) to 116.3 ± 23° (12-m) and 142.3 ± 15° (24-m) (24-m > 12-m, baseline, p = 0.02). External rotation (ER) in adduction changed from 33.1 ± 7° (baseline) to 32.5 ± 4° (12-m) and 53.9 ± 9° (24-m)(24-m > 12-m, baseline, p = 0.01). ER at 90° abduction increased from 56.3 ± 3° (baseline) to 83.5 ± 5° (12-m) and 77.1 ± 4° (24-m) (24-m, 12-m > baseline, p = 0.01). Comparison studies, however, displayed insignificant results with small effect sizes. CONCLUSION: Despite overall fair MCMS scores, at 24-m post-SBSI, shoulder function improved and pain decreased. More rigorous comparative studies, however, revealed insignificant findings. Patients with the potential to re-establish the essential glenohumeral joint force couple that depresses the humeral head on the glenoid fossa and who comply with physical therapy may be more likely to achieve success following SBSI. LEVEL OF EVIDENCE: Level IV.

FITT Odyssey: A Scoping Review of Exercise Programs for Managing Rotator Cuff-Related Shoulder Pain.

OBJECTIVE: To summarize the FITT (frequency, intensity, time, type), components of exercise programs included in randomized controlled trials (RCTs) that compared 2 or more programs for managing rotator cuff-related shoulder pain (RCRSP). DESIGN: Scoping review. LITERATURE SEARCH: Electronic searches were conducted up to May 2023. STUDY SELECTION CRITERIA: RCTs comparing the effects of 2 or more types of exercise programs, differing in prescription according to the FITT principle, in people with RCRSP. DATA SYNTHESIS: We extracted data from each trial report so that we could answer items 1 to 10 and 13 to 15 from the Consensus on Exercise Reporting Template (CERT). Descriptive analysis of the exercise programs was performed by summarizing and presenting the FITT characteristics, and other relevant CERT characteristics (material, provider, delivery, tailoring). RESULTS: FITT characteristics from 46 exercise programs included in 22 trials were extracted. The exercise programs were divided into 4 categories (defined in accordance to the original authors' description and proposed rationale): motor control (n = 8), scapula-focused (n = 7), eccentric (n = 8), and nonspecific exercise programs (n = 28). Five programs were allocated to 2 different categories. The different program types had similar parameters. Exercise programs frequency ranged from 2 to 7 times per week, dose ranged from 1 to 3 sets and 4 to 30 repetitions per sets, and exercise program duration ranged from 4 to 16 weeks. CONCLUSION: There was considerable variability in the parameters used to prescribe exercises for RCRSP. Clinicians seeking guidance on FITT parameters derived from trials should do so cautiously because there was no one-size-fits-all approach. J Orthop Sports Phys Ther 2024;54(8):513-529. Epub 4 June 2024. doi:10.2519/jospt.2024.12452.

The Efficacy of Exercise Therapy for Rotator Cuff-Related Shoulder Pain According to the FITT Principle: A Systematic Review With Meta-analyses.

OBJECTIVE: To evaluate the efficacy of exercise interventions with differing frequency, intensity, type, and time (FITT) on shoulder pain and disability in people with rotator cuff-related shoulder pain (RCRSP). DESIGN: Intervention systematic review with meta-analyses. LITERATURE SEARCH: Electronic searches were conducted up to May 2023. STUDY SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing the effects of exercise interventions differing in prescription according to the FITT principle, in people with RCRSP. DATA SYNTHESIS: Separate meta-analyses comparing exercise type (specific versus nonspecific exercise) and intensity (high versus low) were conducted. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to evaluate the certainty of evidence. RESULTS: Twenty-two RCTs (n = 1281) were included. There was moderate-certainty evidence that motor control exercise programs, when compared to nonspecific exercise programs, significantly reduced disability in the short (SMD: -0.29; 95% CI: -0.51, -0.07; n = 323; 7 RCTs) and medium terms (SMD: -0.33; 95% CI: -0.57, -0.09; n = 286; 5 RCTs), but not pain in the short term (SMD: -0.19; 95% CI: -0.41, 0.03; n = 323; 7 RCTs). Uncertainties remained regarding other exercise types (eccentric and scapula-focused exercise programs) versus nonspecific exercise programs, and exercise intensity due to low- to very low-certainty evidence. No trials were identified that compared different frequencies or times. CONCLUSION: For adults with RCRSP, motor control exercise programs were probably slightly superior to nonspecific exercise programs. However, it is unclear if the effects were due to motor control exercise or to other program characteristics such as progression and tailoring. J Orthop Sports Phys Ther 2024;54(8):499-512. Epub 7 June 2024. doi:10.2519/jospt.2024.12453.

3-Dimensional Bioprinting of a Tendon Stem Cell-Derived Exosomes Loaded Scaffold to Bridge the Unrepairable Massive Rotator Cuff Tear.

BACKGROUND: Unrepairable massive rotator cuff tears (UMRCTs) are challenging to surgeons owing to the severely retracted rotator cuff musculotendinous tissues and extreme defects in the rotator cuff tendinous tissues. PURPOSE: To fabricate a tendon stem cell-derived exosomes loaded scaffold (TSC-Exos-S) and investigate its effects on cellular bioactivity in vitro and repair in a rabbit UMRCT model in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: TSC-Exos-S was fabricated by loading TSC-Exos and type 1 collagen (COL-I) into a 3-dimensional bioprinted and polycaprolactone (PCL)-based scaffold. The proliferation, migration, and tenogenic differentiation activities of rabbit bone marrow stem cells (BMSCs) were evaluated in vitro by culturing them in saline, PCL-based scaffold (S), COL-I loaded scaffold (COL-I-S), and TSC-Exos-S. In vivo studies were conducted on a rabbit UMRCT model, where bridging was repaired with S, COL-I-S, TSC-Exos-S, and autologous fascia lata (FL). Histological and biomechanical analyses were performed at 8 and 16 weeks postoperatively. RESULTS: TSC-Exos-S exhibited reliable mechanical strength and subcutaneous degradation, which did not occur before tissue regeneration. TSC-Exos-S significantly promoted the proliferation, migration, and tenogenic differentiation of rabbit BMSCs in vitro. In vivo studies showed that UMRCT repaired with TSC-Exos-S exhibited significant signs of tendinous tissue regeneration at the bridging site with regard to specific collagen staining. Moreover, no significant differences were observed in the histological and biomechanical properties compared with those repaired with autologous FL. CONCLUSION: TSC-Exos-S achieved tendinous tissue regeneration in UMRCT by providing mechanical support and promoting the trend toward tenogenic differentiation. CLINICAL RELEVANCE: The present study proposes a potential strategy for repairing UMRCT with severely retracted musculotendinous tissues and large tendinous tissue defects.

Factors determining the short-term clinical outcomes of conservative treatment in patients with supraspinatus tear.

INTRODUCTION: To identify factors influencing the better and worse changes in the Western Ontario Rotator Cuff Index of patients undergoing conservative treatment for supraspinatus tendon tear. METHODS: The study included 30 patients with supraspinatus tendon tear who underwent conservative treatment. The average duration of intervention was 35.4 days. The Western Ontario Rotator Cuff Index, shoulder range of motion, isometric muscle strength, supraspinatus tendon thickness, thickness of the supraspinatus, infraspinatus, and teres minor muscles, and acromiohumeral interval were assessed before and after the intervention. In the statistical analyses, change in the Western Ontario Rotator Cuff Index was the dependent variable, and the amount of change in each measurement variable before and after the intervention was the independent variable. RESULTS: The average Western Ontario Rotator Cuff Index improved from 1067 at pre-treatment to 997 at post-treatment, but without a significant difference (p = 0.29). A multiple regression analysis revealed that supraspinatus tendon thickness and muscle strength in shoulder external rotation at 90° scaption had a significant effect on the change in the Western Ontario Rotator Cuff Index (R2 = 0.44, p < 0.01). CONCLUSION: Supraspinatus tendon thickness and muscle strength in shoulder external rotation at 90° scaption were important factors for the Western Ontario Rotator Cuff Index score in the early stages of conservative treatment for patients with supraspinatus tendon tear.

Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.

BACKGROUND: Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study. METHODS: Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats. RESULTS: We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence. CONCLUSION: In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.

Do therapeutic exercises impact supraspinatus tendon thickness? Secondary analyses of the combined dataset from two randomized controlled trials in patients with rotator cuff-related shoulder pain.

BACKGROUND: The mechanistic response of rotator cuff tendons to exercises within the context of rotator cuff-related shoulder pain (RCRSP) remains a significant gap in current research. A greater understanding of this response can shed light on why individuals exhibit varying responses to exercise interventions. It can also provide information on the influence of certain types of exercise on tendons. The primary aim of this article is to explore if changes in supraspinatus tendon thickness (SSTT) ratio differ between exercise interventions (high load vs. low load). The secondary aims are to explore if changes in SSTT ratio differ between ultrasonographic tendinopathy subgroups (reactive vs. degenerative) and if there are associations between tendinopathy subgroups, changes in tendon thickness ratio, and clinical outcomes (disability). METHODS: This study comprises secondary analyses of the combined dataset from two randomized controlled trials that compared high and low-load exercises in patients with RCRSP. In those trials, different exercise interventions were compared: 1) progressive high-load strengthening exercises and 2) low-load strengthening with or without motor control exercises. In 1 trial, there was also a third group that was not allocated to exercises (education only). Ultrasound-assessed SSTT ratio, derived from comparing symptomatic and asymptomatic sides, served as the primary measure in categorizing participants into tendinopathy subgroups (reactive, normal and degenerative) at baseline. RESULTS: Data from 159 participants were analyzed. Two-way repeated measures ANOVAs revealed significant Group (P < .001) and Group × Time interaction (P < .001) effects for the SSTT ratio in different tendinopathy subgroups, but no Time effect (P = .63). Following the interventions, SSTT ratio increased in the "Degenerative" subgroup (0.14 [95% confidence interval {CI}: 0.09-0.19]), decreased in the "Reactive" subgroup (-0.11 [95% CI: -0.16 to -0.06]), and remained unchanged in the "Normal" subgroup (-0.01 [95% CI: -0.04 to 0.02]). There was no Time (P = .21), Group (P = .61), or Group × Time interaction (P = .66) effect for the SSTT ratio based on intervention allocation. Results of the linear regression did not highlight any significant association between the tendinopathy subgroup (P = .25) or change in SSTT ratio (P = .40) and change in disability score. CONCLUSION: Findings from this study suggest that, over time, SSTT in individuals with RCRSP tends to normalize, compared to the contralateral side, regardless of the exercise intervention. Different subgroups of symptomatic tendons behave differently, emphasizing the need to potentially consider tendinopathy subtypes in RCRSP research. Future adequately powered studies should investigate how those different tendinopathy subgroups may predict long-term clinical outcomes.

Potential Misinformation in the Official Disability Guidelines About the Diagnosis and Treatment of Rotator Cuff Tendinopathy.

OBJECTIVE: We selected statements in the Official Disability Guidelines that had the potential to reinforce misconceptions regarding symptoms from rotator cuff tendinopathy. These statements were revised and presented with the original statement to specialists. METHODS: Twelve statements regarding rotator cuff tendinopathy were identified as deviating from principles based on ethics, values, and the evidence regarding both pathophysiology and human illness behavior. One hundred fifteen upper extremity surgeons reviewed both original and revised versions of the statements and indicated their preference. RESULTS: We found that upper extremity surgeons preferred 3 revised statements, 4 Official Disability Guidelines statements, and 5 were rated as neutral between the 2 statements. CONCLUSIONS: Statements revised for evidence, ethics, and healthy mindset were not preferred by specialists, which may indicate limited awareness about how negative thoughts and distressing symptoms impact human illness.

Hierarchical Chiral Calcium Silicate Hydrate Films Promote Vascularization for Tendon-to-Bone Healing.

Revascularization after rotator cuff repair is crucial for tendon-to-bone healing. The chirality of materials has been reported to influence their performance in tissue repair. However, data on the use of chiral structures to optimize biomaterials as a revascularization strategy remain scarce. Here, calcium silicate hydrate (CSO) films with hierarchical chirality on the atomic to micrometer scale are developed. Interestingly, levorotatory CSO (L-CSO) films promote the migration and angiogenesis of endothelial cells, whereas dextral and racemic CSO films do not induce the same effects. Molecular analysis demonstrates that L-chirality can be recognized by integrin receptors and leads to the formation of focal adhesion, which activates mechanosensitive ion channel transient receptor potential vanilloid 4 to conduct Ca2+ influx. Consequently, the phosphorylation of serum response factor is biased by Ca2+ influx to promote the vascular endothelial growth factor receptor 2 signaling pathway, resulting in enhanced angiogenesis. After implanted in a rat rotator cuff tear model, L-CSO films strongly enhance vascularization at the enthesis, promoting collagen maturation, increasing bone and fibrocartilage formation, and eventually improving the biomechanical strength. This study reveals the mechanism through which chirality influences angiogenesis in endothelial cells and provides a critical theoretical foundation for the clinical application of chiral biomaterials.

Effect of extracorporeal shockwave therapy for rotator cuff tendinopathy: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tendinopathy (RCT) is a widespread musculoskeletal disorder and a primary cause of shoulder pain and limited function. The resulting pain and limited functionality have a detrimental impact on the overall quality of life. The purpose of this study was to perform a systematic review of the effects of extracorporeal shock wave therapy (ESWT) for RCT. METHODS: The literature search was conducted on the following databases from inception to February 20, 2024: PubMed, Web of Science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO, and China National Knowledge Infrastructure (CNKI) were checked to identify the potential studies exploring the effect of ESWT for the treatment of Rotator cuff tendinopathy (Calcification or non-calcification), control group for sham, other treatments (including placebo), without restriction of date, language. Two researchers independently screened literature, extracted data, evaluated the risk of bias in the included studies, and performed meta-analysis using RevMan 5.3 software. RESULTS: A total of 16 RCTs with 1093 patients were included. The results showed that compared with the control group, ESWT for pain score Visual Analogue Scale/Score (VAS) (SMD = -1.95, 95% CI -2.47, -1.41, P < 0.00001), function score Constant-Murley score (CMS) (SMD = 1.30, 95% CI 0.67, 1.92, P < 0.00001), University of California Los Angeles score (UCLA) (SMD = 2.69, 95% CI 1.64, 3.74, P < 0.00001), American Shoulder and Elbow Surgeons form (ASES) (SMD = 1.29, 95% CI 0.93, 1.65, P < 0.00001), Range of motion (ROM) External rotation (SMD = 1.00, 95% CI 0.29, 1.72, P = 0.02), Total effective rate (TER) (OR = 3.64, 95% CI 1.85, 7.14, P = 0.0002), the differences in the above results were statistically significant. But ROM-Abduction (SMD = 0.72, 95% CI -0.22, 1.66, P = 0.13), the difference was not statistically significant. CONCLUSION: Currently limited evidence suggests that, compared with the control group, ESWT can provide better pain relief, functional recovery, and maintenance of function in patients with RCT.