Regulatory Role of Collagen XI in the Establishment of Mechanical Properties of Tendons and Ligaments in Mice Is Tissue Dependent.

Collagen XI is ubiquitous in tissues such as joint cartilage, cancellous bone, muscles, and tendons and is an important contributor during a crucial part in fibrillogenesis. The COL11A1 gene encodes one of three alpha chains of collagen XI. The present study elucidates the role of collagen XI in the establishment of mechanical properties of tendons and ligaments. We investigated the mechanical response of three tendons and one ligament tissues from wild type and a targeted mouse model null for collagen XI: Achilles tendon (ACH), the flexor digitorum longus tendon (FDL), the supraspinatus tendon (SST), and the anterior cruciate ligament (ACL). Area was substantially lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Maximum load and maximum stress were significantly lower in Col11a1ΔTen/ΔTen ACH and FDL. Stiffness was lower in Col11a1ΔTen/ΔTen ACH, FDL, and SST. Modulus was reduced in Col11a1ΔTen/ΔTen FDL and SST (both insertion site and midsubstance). Collagen fiber distributions were more aligned under load in both wild type group and Col11a1ΔTen/ΔTen groups. Results also revealed that the effect of collagen XI knockout on collagen fiber realignment is tendon-dependent and location-dependent (insertion versus midsubstance). In summary, this study clearly shows that the regulatory role of collagen XI on tendon and ligament is tissue specific and that joint hypermobility in type II Stickler's Syndrome may in part be due to suboptimal mechanical response of the soft tissues surrounding joints.

Quantifying the Fascicular Changes in Recovered Achilles Tendon Patients Using Diffusion Magnetic Resonance Imaging and Tractography.

Regardless of the way of treatment, persistent deficits in calf muscles in recovered patients from Achilles tendon rupture (ATR) exist long-term postinjury. Studies on calf muscle changes mostly highlight morphological changes in the calf muscles and Achilles tendon. However, limited attention has been given to fascicular changes. Diffusion tensor imaging (DTI) can provide a better understanding of the characteristics and properties of tissues with organized microstructure. In the current study, we used DTI-derived indices (mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues-λ 1, λ 2, and λ 3) and fiber tractography to better understand the soleus muscle after recovery from ATR by comparing the results of injured legs with healthy ones. Our findings suggest that the standard deviations of measured parameters (FA, MD, and eigenvalues) within the soleus muscle are better predictors of the changes associated with the ATR as compared to the control counterpart for the volumetric region of interest (ROI). Additionally, in four out of five participants, smaller tracts were observed in the injured leg compared to the healthy one, as evidenced by the fiber length distribution of the tracts. Altogether, this study demonstrates the feasibility of the DTI and fiber tractography approaches to quantify the fascicular changes in the individuals recovered from ATR.

FGF-2 enriched nanofiber scaffold for advancing achilles tendon healing: a comparative experimental investigation.

Introduction: Achilles tendon rupture is a common and debilitating injury that significantly impacts mobility and quality of life. Effective treatment options that promote faster and more complete healing are needed. Fibroblast growth factor-2 (FGF-2) has shown potential in enhancing tendon repair. This study aims to investigate the efficacy of FGF-2 in promoting tendon healing in a rat model of Achilles tendon rupture, providing insights into its potential as a therapeutic option. Materials and methods: Forty-eight rat hind legs with complete Achilles tendon ruptures were divided into four equal groups: the Sham (S) group (tendon repair only), the Polymer (P) group (tendon repair with scaffold wrapping), the Produced FGF-2 (PF) group (scaffold coated with lab-produced FGF-2), and the Commercial FGF-2 (CF) group (scaffold coated with commercially sourced FGF-2). Histological analyses at two and four weeks post-surgery evaluated healing based on nuclear morphology, vascularity, fibril organization, inflammation, and adipogenesis. Results: At the end of the second week, no macroscopic healing was observed in one rat each from the S and P groups. By the end of the fourth week, macroscopic healing was observed in all groups. The S and P groups exhibited similarly severe fibril disorganization, pathological adipogenesis, and sustained inflammation, particularly at the fourth week. In contrast, the CF group demonstrated improved tendon healing with increased vascularity and extracellular matrix, lower inflammatory cell infiltration, and better fibril organization. Pathological adipogenesis was absent in the CF group, especially at the fourth week. The PF group showed comparable improvements at the second week but experienced a relapse by the 4th week, with increased inflammation and adipogenesis. Conclusion: FGF-2 coated scaffolds significantly enhanced tendon healing in a rat Achilles tendon rupture model by improving fibril organization, increasing vascularity, and reducing inflammation and pathological adipogenesis. These findings suggest that FGF-2 could be a promising therapeutic option for accelerating tendon repair. Future perspectives on tendon repair will focus on enhancing FGF-2 delivery using innovative scaffolds, paving the way for more effective therapies and improved patient outcomes.

Smart hydrogel-based trends in future tendon injury repair: A review.

Despite advances in tissue engineering for tendon repair, rapid functional repair is still challenging due to its specificity and is prone to complications such as postoperative infections and tendon adhesions. Smart responsive hydrogels provide new ideas for tendon therapy with their flexibly designed three-dimensional cross-linked polymer networks that respond to specific stimuli. In recent years, a variety of smart-responsive hydrogels have been developed for the treatment of tendon disorders, showing great research promise and ability to address complex challenges. This article provides a comprehensive review of recent advances in the field of smart-responsive hydrogels for the treatment of tendon disorders, with a special focus on their response properties to different physical, chemical and biological stimuli. The multiple functional properties of these innovative materials are discussed in depth, including excellent biocompatibility and biodegradability, excellent mechanical properties, biomimetic structural design, convenient injectability, and unique self-healing capabilities. These properties enable the smart-responsive hydrogels to demonstrate significant advantages in solving difficult problems in the treatment of tendon disorders, such as precise drug delivery, tendon adhesion prevention and postoperative infection control. In addition, the article looks at the future prospects of smart-responsive hydrogels and analyses the challenges they may face in achieving widespread application.

Acute compartment syndrome of the leg following peroneus longus tendon graft harvesting: case report.

Acute compartment syndrome is a rare donor-site complication of peroneus longus tendon graft harvesting. A case of leg compartment syndrome following peroneus longus tendon harvest for a revision anterior cruciate ligament reconstruction is described. Symptoms began on the first day after surgery, including intense pain in the lateral aspect of the leg and dorsum of the foot, and motor and sensory deficits of the common peroneal nerve. Emergency decompressive fasciotomy was necessary. The patient presented a complete resolution of symptoms and neurological deficit 24 days after surgery. Surgeons harvesting this graft should keep in mind the possibility of this complication in case of unusual pain in the early postoperative period, so that they can quickly diagnose and treat this threatening condition.

Association of Anterior Knee Pain With Extension Deficit After Anterior Cruciate Ligament Reconstruction: A Systematic Review.

Background: Previous systematic reviews have reported the incidence of anterior knee pain (AKP) and extension deficit (ED) after anterior cruciate ligament reconstruction (ACLR); however, both outcomes are estimated separately and thus are assumed to be uncorrelated. Purpose: To estimate whether there is a clinically relevant association between the population effects of ED and AKP after ACLR. Study Design: Systematic review; Level of evidence, 2. Methods: Under PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted by searching PubMed, EMBASE, and the Cochrane Library electronic databases for published articles reporting incidence of both AKP and ED after ACLR with either bone-patellar tendon-bone (BPTB) or hamstring (HS) graft that returned 298 studies after the initial search. A Bayesian hierarchical measurement error model estimated the population effect of ED and AKP. Results: Twelve publications involving 976 patients (mean follow-up, 77.9 months; range, 24-180 months) were included in the systematic review. There was a clear, moderate correlation between population ED and population AKP for the BPTB (r = 0.40; 95% CI, 0.39-0.42) and the HS grafts (r = 0.35; 95% CI, 0.33-0.36). Model expected estimates for the population effects of AKP and ED were 24.1% (95% CI, 17.4%-31.9%) and 17.5% (95% CI, 10.6%-25.0%), respectively, for the BPTB graft and 16.1% (95% CI, 9.2%-23.9%) and 13.1% ED (95% CI, 6.0%-20.8%) for the HS graft, respectively. The posterior mean difference in AKP between BPTB and HS grafts was clear and substantial (8.3% [95% CI, 0.3% to 16.1%]); there was no substantial difference in the posterior mean difference of ED between BPTB and HS grafts (4.3% [95% CI, -3.8% to 13.0%). Conclusion: Our systematic review demonstrated a moderate but clear correlation between ED and AKP irrespective of graft type. From a clinical perspective, this association emphasizes the need for intraoperative achievement of full extension and avoidance of situations that may cause ED. The higher incidence of AKP in patients with BPTB graft may also be attributed to factors related to the graft harvest site. Future metaregression analyses could investigate whether additional factors such as follow-up duration or rehabilitation protocols can moderate the association between AKP and ED after ACLR with either BPTB or HS graft.

The Difference in Achilles Tendon Loading within Immobilizing Boots Based on Ankle Angle, Boot Type, and Walking Speed.

Background: Achilles tendon rupture is an increasingly common injury treated with progressive rehabilitation in an immobilizing boot. However, it is poorly understood how ankle angle, boot type, and walking speed affect Achilles tendon loading. Hypothesis: These different parameters would affect Achilles tendon loading in terms of (from greatest to least) ankle angle constraint, immobilization style, boot construction, and walking speed. Study Design: Descriptive laboratory study. Methods: Ten healthy young adults (8 women and 2 men; age, 21 ± 2 years; body mass index, 21.5 ± 3.0 kg/m2) walked in 3 different immobilizing boots at self-selected slow, medium, and fast walking speeds. The authors estimated Achilles tendon loading using a 3-part instrumented insole within the immobilizing boot. The authors averaged tendon load across every stride for each condition and calculated 2-sided bootstrap confidence intervals. Peak tendon loading was compared across all boots, ankle angles, and walking speeds. Results: All boots and immobilization styles decreased tendon loading with respect to shod walking. Immobilization angle had the largest effect on tendon loading, followed by boot construction, and finally walking speed. Conclusion: Ankle angle, boot type, and walking speed can be modified to change loading progression during rehabilitation. Clinical Relevance: Understanding how immobilization affects tendon loading will enable clinicians to modify rehabilitation to improve functional outcomes.

A Comparative Study on Arthroscopic Superior Capsular Reconstruction Using Fascia Lata Autograft With and Without Long Head of the Biceps Tendon Augmentation: Two-Year Patient-Reported Outcomes and Radiographic Analysis.

Background: Given the growing concerns regarding objective measures of clinical outcomes, attention has recently been devoted to the establishment of clinically significant outcome (CSO) thresholds for patient-reported functional scores after rotator cuff surgery. Purpose: To retrospectively compare patient-reported outcome (PRO) measures (PROMs) and radiographic data between patients who underwent arthroscopic superior capsular reconstruction (SCR) with and without long head of the biceps tendon (LHBT) augmentation. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 43 patients receiving arthroscopic SCR between 2016 and 2020 were enrolled, including a biceps augmentation group (n = 27) and a nonaugmentation group (n = 16). Patients were asked an anchor question regarding their satisfaction and perception of improvements. PROMs of American Shoulder and Elbow Surgeons (ASES), Constant score, Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) for pain scores and radiographic data including magnetic resonance imaging and plain radiographs were collected and compared between the 2 groups. Anchor questions in CSO analysis for deriving the minimal clinically importance difference (MCID), substantial clinical benefit (SCB), Patient Acceptable Symptom State (PASS), and maximal outcome improvement (MOI) values were applied ≥2 years postoperatively. Results: Based on satisfaction responses, 17 patients were classified as satisfied, 16 as unsatisfied, and 10 as fair. Additionally, 13 patients felt they were improved, 14 changed, and 16 unchanged. Intergroup comparison based on patients' satisfaction and perception of change or improvement exhibited significant differences in all 4 functional scores in favor of the satisfied and improved patients. However, there was no significant difference in the ΔVAS scores between the groups. CSO analyses showed no significant difference in percentage of patients achieving MCID, SCB, and PASS thresholds for the ΔASES, ΔConstant, and ΔSANE scores between patients undergoing arthroscopic SCR with or without LHBT augmentation. A significant difference was found in the percentage of patients achieving the MOI for ΔASES score with 70.4% in the augmented group and 37.5% in the nonaugmented group, respectively. The mean acromiohumeral distance (AHD) differed significantly between augmentation (8.1 ± 2.2 mm) and nonaugmentation (7 ± 1.9 mm) groups. The graft tear rate did not differ significantly. Conclusion: There was no significant difference in PROs and percentage of patients achieving MCID, SCB, and PASS between isolated and augmented SCR groups. A higher percentage of patients achieving MOI and slightly greater AHD were found in the augmented group. Further evaluation is required to determine if there is any long-term benefit to LHBT augmentation of SCR.

Role of the Conjoined Tendon in Hip Stability Post-Total Hip Arthroplasty: Insights From a Direct Anterior Approach Cadaver Study.

Background: Hip dislocation represents a significant complication encountered following hip arthroplasty procedures. In this investigation, we conducted a comparative analysis of the biomechanical characteristics exhibited by the piriformis and the conjoined tendon after total hip arthroplasty (THA) via the direct anterior approach (DAA), utilizing cadaveric specimens. The objective is to ascertain the relative significance of the piriformis muscle and the conjoined tendon in mitigating hip dislocation. Methods: A total of 16 hip joints from 8 freshly frozen cadavers were selected and stratified into 2 groups: the piriformis tendon (PT) group and the conjoined tendon (CT) group. Following THA via the DAA, measurements were taken to record the torque required to induce hip dislocation under various conditions. Torque readings were obtained with the tendon in its intact state (intact group) and after preservation or reconstruction of either the PT or the CT. Results: The torques of anterior and posterior dislocation in PT group were 22.24 ± 4.53 N.m and 30.7 ± 15.5 N.m following tendon severed, and 20.04 ± 2.67 N.m and 17.5 ± 6.7 N.m following reconstruction. There were no differences compared to the intact group. The torque decreased in the CT group after CT was severed with the torques dropping from 31.2 ± 7.6 N.m to 8.18 ± 2.6 N.m (P < .0001) for anterior dislocation, and from 34.9 ± 8.3 N.m to 9.8 ± 2.8 N.m (P < .0001) for posterior dislocation. Following reconstruction, the torque required for dislocation significantly increased (P < .0001). Conclusions: This study underscores the preeminent role of the CT in ensuring hip stability following THA via DAA, highlighting the cruciality of its preservation and reconstruction during surgical interventions.

Fear of reinjury after acute Achilles tendon rupture is related to poorer recovery and lower physical activity postinjury.

Purpose: The aim of this study was to investigate how fear of reinjury to the Achilles tendon affects return to previous levels of physical activity and self-reported Achilles tendon Total Rupture Score (ATRS) outcomes. Methods: Data were collected from a large cohort of patients treated for an acute Achilles tendon rupture at Sahlgrenska University Hospital Mölndal between 2015 and 2020. The ATRS and additional questions concerning fear of reinjury, treatment modality, satisfaction of treatment and recovery were analyzed 1-6 years postinjury. Analysis was performed to determine the impact of fear of reinjury on patient-reported recovery and physical activity. Results: Of a total of 856 eligible patients, 550 (64%) answered the self-reported questionnaire and participated in the follow-up. Of the participants, 425 (77%) were men and 125 (23%) were women. ATRS, recovery in percentage, satisfaction of treatment, recovery on a 5-point scale and physical activity level post- versus preinjury were significantly related to fear of reinjury (p < 0.001). Of the nonsurgically treated patients, 59% reported fear of reinjury compared to 48% of the surgically treated patients (p = 0.024) Patients that reported fear of reinjury had a 15-point lower median ATRS score than those who did not (p < 0.001). Conclusion: More than half of patients who have suffered an Achilles tendon rupture are afraid of reinjuring their tendon. Patients who reported fear of reinjury exhibited a significantly lower ATRS score. This indicates the importance of addressing psychological aspects in the treatment after this injury. Level of Evidence: Level II.

Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones.

Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (n = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by µCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes Sclerostin (Sost) and Periostin (Postn) was not impacted by the exercise in long bones. Oppositely, Sost and Postn levels were modulated by exercise in joints, and osteogenic markers (Col10a1, Runx2, Osx, and Dmp1) were downregulated in the exercise group. In addition, the tenogenic markers Scx, Mkx, and Tnmd were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of Bmp2, Bmp4, and Id1 was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.

Allograft to bone-tunnel integration in a canine anterior cruciate ligament reconstruction model: a comparison study of allograft preparation methods.

The procedure of anterior cruciate ligament (ACL) allograft preparation can be divided into fresh-frozen method (FF-allograft) or freeze-dried method (FD-allograft). This study aims to biomechanically and histologically compare the graft to bone tunnel integration between the two allografts. In-vitro results indicated that FF-allograft and FD-allograft showed excellent biocompatibility and biomechanics, while FD-allograft showed a denser collagen fiber arrangement than FF-allograft and autograft. Then, in-vivo preformation of the FF-allograft, FD-allograft, and autograft on bone tunnel integration was evaluated via a canine ACL reconstruction model. In-vivo results indicated that no signs of infection or osteoarthritis were shown in the femur-graft-tibia complexes, but more vascularity and synovitis formed around the implanted FF-allograft. Micro-computed tomography showed that peri-graft bone in the FF-allograft group was significantly increased and remodeled compared with the FD-allograft group; Histologically, the FF-allograft group exhibited similar graft-bone tunnel healing to the FD-allograft group. Tartrate-resistant acid phosphatase (TRAP) staining showed significantly more osteoclasts presented in the FD-allograft group compared to the FF-allograft group. Meanwhile, a significantly higher failure load was shown in the FF-allograft group when compared with the FD-allograft group (P < 0.05). In conclusion, the FF-allograft integrated more firmly into the bone tunnel than the FD-allograft when used in ACL reconstruction.

How statistically fragile are randomized controlled trials comparing quadriceps tendon autografts with hamstring or bone-patellar tendon-bone autografts in anterior cruciate ligament reconstruction?

PURPOSE: To determine the statistical fragility of randomized controlled trials (RCTs) which compare the use of quadriceps tendon (QT) autografts to either hamstring tendon (HT) or bone-patellar tendon-bone (BPTB) autografts in anterior cruciate ligament reconstruction (ACLR). METHODS: A search was conducted across PubMed, MEDLINE and EMBASE databases for RCTs comparing QT autografts to HT or BPTB autografts in ACLR from inception to 21 April 2024. Studies that reported ≥1 statistically significant continuous outcome, statistically significant dichotomous outcome and/or nonsignificant dichotomous outcome were included for analysis. The fragility index (FI), continuous fragility index (CFI) and reverse fragility index (RFI) were calculated for significant dichotomous outcomes, significant continuous outcomes and nonsignificant dichotomous outcomes, respectively. RESULTS: A total of 11 RCTs comprising 716 patients were included. The mean sample size was 65.8 patients. The median FI among nine outcomes from four studies was 1.0 (interquartile range [IQR], 0.5; 95% confidence interval [CI], 0.6-1.4; range 0.5-1.5). The number of patients lost to follow-up at the final follow-up period was more than the study-specific FI in three (75%) studies. The median CFI among 30 outcomes from six studies was 4.9 (IQR, 10.1, 95% CI, 3.9-8.2; range 0-18.2). The number of patients lost to follow-up at the final follow-up period was more than the study-specific CFI in four (66.7%) studies. The median RFI among 10 outcomes from five studies was 5.0 (IQR, 3.5; 95% CI, 3.4-6.6; range 1.0-9.0). The number of patients lost to follow-up at the final follow-up period was more than the study-specific RFI in four (80%) studies. CONCLUSION: This systematic review revealed that regardless of the metric used, RCTs comparing QT autografts to HT or BPTB autograft options in ACLR are statistically fragile. While the indices of statistical fragility evaluated in this study are important metrics of robustness to consider, their application in research and clinical practice needs to be further elucidated. LEVEL OF EVIDENCE: Level I.

Fabrication of MnO2-Modified Decellularized Tendon Membrane for Enhancing Tendon Repair.

Repairing tendon/ligament injuries is a major challenge in sports medicine. It has been reported that tendon injury healing is hindered by massive production of reactive oxygen species (ROS). Manganese oxides nanoparticles are generally non-toxic, can scavenge ROS, promote tissue regeneration, and hold promise for sustainable nanotechnologies. However, the effective and safe integration of MnO2 nanoparticles on decellularized scaffold mediating tissue repair is still a great challenge. To address these issues, an in situ MnO2-modified decellularized scaffold is developed to enhance tendon regeneration through improving microenvironment. The decellularized fibrous membrane is designed and prepared using the central tendon of the porcine diaphragm. Then MnO2 nanozymes are in situ grown on the collagen fibers using tannic acid (TA) as cross-linking agent and reducing agent. The results showed that MnO2-modified scaffold eliminates excessive accumulation of ROS in cells, protects mitochondrial, and maintains the phenotype of tendon cells in an oxidative stress environment. Notably, it is found that the MnO2-modified scaffold exhibits good biocompatibility and is able to promote the tendon healing in the rat patellar tendon defect model. Altogether, this study confirmed that this nanozyme-functionalized decellularized extracellular matrix effectively enhanced tendon repair by scavenging ROS, which provides new strategies for enhancing tendon regeneration.

Tissue-engineered collagen matrix loaded with rat adipose-derived stem cells/human amniotic mesenchymal stem cells for rotator cuff tendon-bone repair.

The rotator cuff tendon-bone interface tissue exhibits high heterogeneity in its composition and structure, with collagen being its primary component. Here, we prepared tissue-engineered decellularized live hyaline cartilage grafts (dLHCG), this dLHCG scaffold's bioactive ECM mainly consists of collagen II, proteoglycans, and fibronectin, presenting a cartilage-like lacuna microstructure. The dLHCG scaffold loaded human amniotic mesenchymal stem cells (hAMSCs) and adipose stem cells (ADSCs) were implanted into the interface. The dLHCG scaffold could maintain the pluripotency of stem cells, supporting the proliferation, osteogenic differentiation, and tenogenic differentiation of the MSCs. The collagen II, through the integrin α2ß1-FAK-JNK signaling axis, promotes Runx-2 activation, playing a better regulatory role in the early osteogenic differentiation of MSCs, enhancing bone defect repair through an endochondral ossification process. The in vivo rat model demonstrated that 12 weeks post-operation, the MSC-loaded dLHCG scaffold group exhibited continuous aligned collagen fibers at the tendon-bone interface, with significantly enhanced biomechanical function compared to the control group. The dLHCG scaffold create an efficient interface, which promoting the restoration of the soft-hard gradient structure tissue at the junction between the scaffold and the host tissue, thereby providing a rational and promising strategy for the rapid healing of the rotator cuff injury.

ACR Appropriateness Criteria® Acute Elbow and Forearm Pain.

Acute elbow pain can be the result of traumatic and atraumatic processes. Pathologic processes include osseous, ligamentous, and tendinous etiologies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis.

OBJECTIVES: Enthesitis is considered a hallmark of psoriatic arthritis (PsA). The objective was to assess clinical enthesitis in PsA including its prevalence in different contexts, scores used and consequences of enthesitis. METHODS: A systematic literature review with meta-analysis was conducted in PubMed 2010-2023, focusing on manuscripts involving adult PsA patients and reporting information related to enthesitis. Data collected included the prevalence of clinical enthesitis (i.e., number of patients with at least one enthesitis); scores used: Leeds Enthesitis Index (LEI), MASES, SPARCC; and impact of enthesitis on disease activity, patient-reported outcomes and use of analgesics. Univariate random-effects meta-analysis was applied for pooling percentages and means. RESULTS: Overall, 212 studies, i.e., 84,262 PsA patients were analyzed. The pooled prevalence of enthesitis in the overall population was 41.6% [95% confidence interval, 37.4-45.8]; with 67.2% [62.0-72.6] in trials and 27.8% [24.5-31.2] in observational studies. The number of enthesitis varied according to the score used, with the lowest observed for the LEI which was the most widely-used score (63.7%). Patients with enthesitis had higher disease activity and disease burden in comparison with those without enthesitis. CONCLUSION: Enthesitis is a frequent manifestation in PsA, concerning close to half the patients, and is more prevalent in trials than in observational studies, reflecting recruitment patterns. The clinical assessment of enthesitis remains challenging, with heterogeneity in the scores used influencing the results: the most used score was the LEI which also led to the lowest prevalence of enthesitis. Links with patients' quality of life should be further explored.

Leveraging in vivo animal models of tendon loading to inform tissue engineering approaches.

Tendon injuries disrupt successful transmission of force between muscle and bone, resulting in reduced mobility, increased pain, and significantly reduced quality of life for affected patients. There are currently no targeted treatments to improve tendon healing beyond conservative methods such as rest and physical therapy. Tissue engineering approaches hold great promise for designing instructive biomaterials that could improve tendon healing or for generating replacement graft tissue. More recently, engineered microphysiological systems to model tendon injuries have been used to identify therapeutic targets. Despite these advances, current tissue engineering efforts that aim to regenerate, replace, or model injured tendons have largely failed due in large part to a lack of understanding of how the mechanical environment of the tendon influences tissue homeostasis and how altered mechanical loading can promote or prevent disease progression. This review article draws inspiration from what is known about tendon loading from in vivo animal models and identifies key metrics that can be used to benchmark success in tissue engineering applications. Finally, we highlight important challenges and opportunities for the field of tendon tissue engineering that should be taken into consideration in designing engineered platforms to understand or improve tendon healing.

A Tympanic Piezo-Bioreactor Modulates Ion Channel-Associated Mechanosignaling to Stabilize Phenotype and Promote Tenogenesis in Human Tendon-Derived Cells.

Preserving the function of human tendon-derived cells (hTDCs) during cell expansion is a significant challenge in regenerative medicine. In this study, a non-genetic approach is introduced to control the differentiation of hTDCs using a newly developed tympanic bioreactor. The system mimics the functionality of the human tympanic membrane, employing a piezoelectrically tuned acoustic diaphragm made of polyvinylidene fluoride-co-trifluoroethylene and boron nitride nanotubes. The diaphragm is vibrationally actuated to deliver targeted electromechanical stimulation to hTDCs. The results demonstrate that the system effectively maintains the tendon-specific phenotype of hTDCs, even under conditions that typically induce nonspecific differentiation, such as osteogenesis. This stabilization is achieved by modulating integrin-mediated mechanosignaling via ion channel-regulated calcium activity, potentially by TREK-1 and PIEZO1, yet targeted studies are required for confirmation. Finally, the system sustains the activation of key differentiation pathways (bone morphogenetic protein, BMP) while downregulating osteogenesis-associated (mitogen-ctivated protein kinase, MAPK and wingless integrated, WNT) pathways and upregulating Focal Adhesion Kinase (FAK) signaling. This approach offers a finely tunable, dose-dependent control over hTDC differentiation, presenting significant potential for non-genetic approaches in cell therapy, tendon tissue engineering, and the regeneration of other mechanosensitive tissues.

Increasing or decreasing load during resistance training is not associated with changes in pain among individuals with patellar tendinopathy: a randomized crossover study.

OBJECTIVES: This study investigated whether exercising with different relative loads would be associated with different experienced pain intensities in individuals with patellar tendinopathy. MATERIALS AND METHODS: We recruited 14 individuals with patellar tendinopathy for this randomized crossover study. In a randomized order, participants performed one set of single-legged leg presses during one session with three relative loads (6 repetition maximum (RM), 10RM, and 14RM). The primary outcome was pain during exercise measured on a 0-10 Numerical Rating Scale (NRS) (0 = no pain, 10 = worst pain), which participants rated after performing the exercise set with each relative load. RESULTS: No differences in pain during either of the three relative loads were observed (F(2, 26) = 0.06, p = 0.942). The participants' experienced pain was 4.5 NRS (SD1.7), 4.5 NRS (SD1.7), and 4.6 NRS (SD2.0) during the 6RM, 10RM, and 14RM loads, respectively. A secondary analysis revealed no statistically significant difference in pain intensity between the performance of the first, second, or third exercise set regardless of the load (F(2, 26) = 1.06, p = 0.367). CONCLUSIONS: There was no difference in pain intensity during either relative load among individuals with patellar tendinopathy. Therefore, higher loads may be applied, associated with enhanced tendon adaptation.

Clinicians may tend to decrease the load if the patient suffering from patellar tendinopathy expresses pain despite no evidence supporting that reducing the load will change the pain intensity during exercise.This study found that all loads (6RM, 10RM, and 14RM) were associated with the same pain experience.Pain did not vary with different exercise loads and, therefore, should not be used as the primary guide for load selection.