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.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

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.

Investigation of the pressure value while performing biceps tenodesis for superior capsuler reconstruction.

BACKGROUND: To compare the histopathological results of biceps tenodesis (BT) performed with normal, low, and high pressures for superior capsule reconstruction (SCR) in rabbits with massive rotator cuff tears. MATERIALS AND METHODS: Thirty rabbits were divided into three groups. Rabbits 1-10 underwent SCR with BT at the same pressure (Group 1), value measured in the groove; 50% lower (Group 2); 50% higher (Group 3). After the 4-week follow-up, shoulder were en-bloc excised and histopathological evaluation was performed with modified Bonar's scale. Results were compared between the groups, statistically. RESULTS: Extracellular matrix were significantly lower in group 2 compared to the other groups (p < 0.05). Cellularity levels were significantly lower in group 2 compared to the other groups (p < 0.05). Group 2 had no difference between the sides (p > 0.05). Group 2 had lower vascularity levels compared to the other groups (p = 0.01). DICSUSSION: When the biceps tendon was in the bicipital groove and in a more mobile state with lower pressure exposure. BT performed with a tension that creates less pressure than the biceps in the groove is more successful in SCR.

Malvidin attenuates trauma-induced heterotopic ossification of tendon in rats by targeting Rheb for degradation via the ubiquitin-proteasome pathway.

The pathogenesis of trauma-induced heterotopic ossification (HO) in the tendon remains unclear, posing a challenging hurdle in treatment. Recognizing inflammation as the root cause of HO, anti-inflammatory agents hold promise for its management. Malvidin (MA), possessing anti-inflammatory properties, emerges as a potential agent to impede HO progression. This study aimed to investigate the effect of MA in treating trauma-induced HO and unravel its underlying mechanisms. Herein, the effectiveness of MA in preventing HO formation was assessed through local injection in a rat model. The potential mechanism underlying MA's treatment was investigated in the tendon-resident progenitor cells of tendon-derived stem cells (TDSCs), exploring its pathway in HO formation. The findings demonstrated that MA effectively hindered the osteogenic differentiation of TDSCs by inhibiting the mTORC1 signalling pathway, consequently impeding the progression of trauma-induced HO of Achilles tendon in rats. Specifically, MA facilitated the degradation of Rheb through the K48-linked ubiquitination-proteasome pathway by modulating USP4 and intercepted the interaction between Rheb and the mTORC1 complex, thus inhibiting the mTORC1 signalling pathway. Hence, MA presents itself as a promising candidate for treating trauma-induced HO in the Achilles tendon, acting by targeting Rheb for degradation through the ubiquitin-proteasome pathway.

Effects of adipose-derived cell supplementation on tendon-bone healing in a rat model of chronic rotator cuff tear with suprascapular nerve injury.

OBJECTIVE: To investigate the effect of adipose-derived cells (ADCs) on tendon-bone healing in a rat model of chronic rotator cuff tear (RCT) with suprascapular nerve (SN) injury. METHODS: Adult rats underwent right shoulder surgery whereby the supraspinatus was detached, and SN injury was induced. ADCs were cultured from the animals' abdominal fat. At 6 weeks post-surgery, the animals underwent surgical tendon repair; the ADC (+ve) group (n = 18) received an ADC injection, and the ADC (-ve) group (n = 18) received a saline injection. Shoulders were harvested at 10, 14, and 18 weeks and underwent histological, fluorescent, and biomechanical analyses. RESULTS: In the ADC (+ve) group, a firm enthesis, including dense mature fibrocartilage and well-aligned cells, were observed in the bone-tendon junction and fatty infiltration was less than in the ADC (-ve) group. Mean maximum stress and linear stiffness was greater in the ADC (+ve) compared with the ADC (-ve) group at 18 weeks. CONCLUSION: ADC supplementation showed a positive effect on tendon-bone healing in a rat model of chronic RCT with accompanying SN injury. Therefore, ADC injection may possibly accelerate recovery in massive RCT injuries.

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.

Mechanical overload-induced release of extracellular mitochondrial particles from tendon cells leads to inflammation in tendinopathy.

Tendinopathy is one of the most common musculoskeletal diseases, and mechanical overload is considered its primary cause. However, the underlying mechanism through which mechanical overload induces tendinopathy has not been determined. In this study, we identified for the first time that tendon cells can release extracellular mitochondria (ExtraMito) particles, a subtype of medium extracellular particles (mEPs), into the environment through a process regulated by mechanical loading. RNA sequencing systematically revealed that oxygen-related reactions, extracellular particles, and inflammation were present in diseased human tendons, suggesting that these factors play a role in the pathogenesis of tendinopathy. We simulated the disease condition by imposing a 9% strain overload on three-dimensional mouse tendon constructs in our cyclic uniaxial stretching bioreactor. The three-dimensional mouse tendon constructs under normal loading with 6% strain exhibited an extended mitochondrial network, as observed through live-cell confocal laser scanning microscopy. In contrast, mechanical overload led to a fragmented mitochondrial network. Our microscopic and immunoblot results demonstrated that mechanical loading induced tendon cells to release ExtraMito particles. Furthermore, we showed that mEPs released from tendon cells overloaded with a 9% strain (mEP9%) induced macrophage chemotaxis and increased the production of proinflammatory cytokines, including IL-6, CXCL1, and IL-18, from macrophages compared to mEP0%, mEP3%, and mEP6%. Partial depletion of the ExtraMito particles from mEP9% by magnetic-activated cell sorting significantly reduced macrophage chemotaxis. N-acetyl-L-cysteine treatment preserved the mitochondrial network in overloaded tendon cells, diminishing overload-induced macrophage chemotaxis toward mEP9%. These findings revealed a novel mechanism of tendinopathy; in an overloaded environment, ExtraMito particles convey mechanical response signals from tendon cells to the immune microenvironment, culminating in tendinopathy.

Finger flexor rigidity in the healthy population.

The involvement of the hand flexors in trigger finger is not clear. This study aimed to examine the rigidity of the flexor tendon in the first pulley territory in the hand by using ultrasound in a healthy population, as well as to create a reference scale of rigidity for the flexor tendons to compare those values in trigger fingers. We tested 35 healthy volunteers using a linear ultrasound transducer and the color Doppler method. Rigidity levels below the first pulley were examined and compared between the different fingers of the hand and the relationship between rigidity and sex and the three different age groups was evaluated. In the healthy population, the rigidity of the flexor tendons of the hand in the territory of the first pulley varied between 233.1 and 962.8 kPa, with an average of 486.42 kPa and standard deviation of 114.85. We showed that the flexors in the dominant hand were more rigid, there was a difference between the rigidity of the flexor tendons of the thumb and the other fingers of the same hand, and the ring finger of the dominant hand had stiffer flexor tendons than the fingers of the other hand in the male population. We created a value scale for the rigidity of the flexor tendons of the fingers. This base scale can be compared between different pathologies, including trigger finger. The study and all experimental protocols were approved by the local ethical committee.

MRI findings of peroneal tendon tears do not necessarily correlate to clinical findings in paediatric and adolescent patients.

PURPOSE: Pathologic abnormality of the peroneal tendons are thought to be an under-appreciated source of vague ankle and hindfoot pain in paediatric patients, partly because they can be difficult to diagnose and differentiate from lateral ankle ligament injuries. While magnetic resonance imaging (MRI) is the primary imaging modality used to detect peroneal tendon pathology, previous studies in adults have found that positive MRIs demonstrate a positive predictive value (PPV) of associated clinical findings around 48%. There are no similar known published studies in the paediatric population. Our objective was to determine the positive predictive value of peroneal tendon pathology as diagnosed by MRI as related to positive clinical exam findings in the paediatric and adolescent population. METHODS: This IRB approved retrospective study was conducted at a tertiary children's hospital. Inclusion criteria included patients under 18 years from our tertiary care institution with (a) ankle MRI findings indicating pathology of the peroneus brevis/longus tendons confirmed by a board certified paediatric musculoskeletal radiologist and (b) formal review of the clinical examination by a fellowship trained paediatric orthopaedic surgeon. Patients with congenital deformities or previous surgical intervention of the lateral ankle were excluded. RESULTS: Forty-seven patients (with 48 MRIs) met inclusion criteria over a ten year period. The majority of the positive MRI scans (70%) demonstrated a peroneus brevis split tear. Of the patients with positive findings on MRI, 17 patients had an associated positive clinical exam. The positive predictive value of MRI for peroneal tendon tears with positive clinical findings was 35.41% (95% confidence interval = 31.1% to 41.6%). There were 31 patients with MRI positive findings with a negative clinical exam. CONCLUSION: Despite having a negative clinical exam, a high percentage of patients had positive MRI findings suggestive of peroneal tendon pathology which confirms findings of adult populations demonstrating a high rate of incidental finding of peroneal tendon pathology on MRI in paediatric patients.

Optimized design of an enthesis-mimicking suture anchor-tendon hybrid graft for mechanically robust bone-tendon repair.

Repair of functionally graded biological interfaces requires joining dissimilar materials such as hard bone to soft tendon/ligament, with re-injuries/re-tears expected to be minimized by incorporating biomimicking, stress-reducing features within grafts. At bone-tendon interfaces (entheses), stress can be reduced via angled insertion, geometric flaring, mechanical gradation, and interdigitation of tissues. Here, we incorporated enthesis attributes into 3D in silico and physical models of a unique suture anchor-tendon hybrid graft (SATHG) and investigated their effects on stress reduction via finite element analyses (FEA) studies. Over 20 different simulations altering SATHG angulation, flaring, mechanical gradation, and interdigitation identified an optimal design, which included 90° angulation, 25° flaring, and a compliant (ascending then descending) mechanical gradient in SATHG's bone-to-tendon-like transitional region. This design reduced peak stress concentration factor (SCF) by 43.6 % relative to an ascending-only mechanical gradient typically used in hard-to-soft tissue engineering. To verify FEA results, SATHG models were fabricated using a photocrosslinkable bone-tendon-like polyurethane (QHM polymer) for ex vivo tensile assessment. Tensile testing showed that ultimate load (132.9 N), displacement-at-failure (1.78 mm), stiffness (135.4 N/mm), and total work-to-failure (422.1 × 10-3 J) were highest in the optimized design. Furthermore, to assess envisioned usage, SATHG pull-out testing and 6-week in vivo implantation into large, 0.5-cm segmental supraspinatus tendon defects was performed. SATHG pull-out testing showed secure bone attachment while histological assessment such as hematoxylin and eosin (H&E) together with Safranin-O staining showed biocompatibility including enthesis regeneration. This work demonstrates that engineering biomaterials with FEA-optimized, enthesis-like attributes shows potential for enhancing hard-to-soft tissue repair. STATEMENT OF SIGNIFICANCE: Successful repair of hard-to-soft tissue injuries is challenging due to high stress concentrations within bone-tendon/ligament grafts that mechanically compromise repair strength. While stress-reducing gradient biomaterials have been reported, little-to-no attention has focused on other bone-tendon/ligament interface (enthesis) features. To this end, a unique bone-tendon graft (SATHG) was developed by combining two common orthopaedic devices along with biomimetic incorporation of four enthesis-like features to reduce stress and encourage widespread clinician adoption. Notably, utilizing designs based on natural stress dissipation principles such as anchor insertion angle, geometric flaring, and mechanical gradation reduced stress by 43.6 % in silico, which was confirmed ex vivo, while in vivo studies showed SATHG's ability to support native enthesis regeneration. Thus, SATHG shows promise for hard-to-soft tissue repairs.

Spontaneous tendon or ligament ruptures in patients undergoing dialysis: First pediatric case report and literature review.

Spontaneous tendon or ligament ruptures are quite rare and mostly associated with chronic systemic diseases such as diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney disease (CKD). In this study, we present the first documented case of a spontaneous rupture of the medial patellofemoral ligament (MPFL) in a pediatric patient. The patient was undergoing long-term peritoneal dialysis (PD) and had a history of severe secondary hyperparathyroidism. Additionally, we discussed spontaneous tendon and ligament ruptures associated with CKD or dialysis through a comprehensive literature review. This case report highlights the importance of recognizing that spontaneous tendon or ligament injuries are not exclusive to adults; children with CKD can also be affected. Several factors including poor parathyroid hormone (PTH) and metabolic acidosis control, prolonged CKD duration and presence of malnutrition play role in the pathogenesis. Early diagnosis is crucial as it allows for timely surgical intervention and leads to a favorable functional recovery.

The 2D and 3D MR arthrographic description of aponeurotic expansion of supraspinatus tendon and biceps tendon anomaly in a large patient cohort.

OBJECTIVE: To describe the aponeurotic expansion of supraspinatus tendon (AEST) and biceps tendon abnormalities with magnetic resonance (MR) arthrographic examinations and determine their prevalence in patients, we performed a high-resolution 3D direct MR arthrography. MATERIALS AND METHODS: This was a retrospective study of 700 shoulder MR arthrograms performed between May 2010 and January 2022. Extension in the coronal plane of an AEST on 3D fat-suppressed T1-weighted volumetric interpolated breath-hold examination (VIBE) MR arthrography was identified. Based on its morphology, the AEST on MR arthrography was divided into four subtypes: absence of tendinous thickness in the bicipital synovial surface or intra-synovial tendon-like structure in the bicipital groove, thin and flat tendinous thickness ≥1 mm of bicipital synovium, oval tendinous structure less than half the size of the adjacent biceps tendon, oval tendinous structure more than half the size of the adjacent biceps tendon, and oval tendinous structure larger than the adjacent biceps tendon. Based on its origin and termination, aponeurotic expansions can be divided into three subtypes: proximal pulley zone, middle humeral neck zone, and distal myotendinous junction zone. Association with the biceps synovium of the AEST was categorized into three types: intra-synovial, extra-synovial, and trans-synovial. RESULTS: An AEST in the anterior shoulder joint in 3D VIBE MR arthrography images was identified in 63 (9%) of 700 arthrograms. The most common arthrographic type of AEST was type 1-this was detected in 39 of 63 patients. The most common course type of the AEST was anteriorly midline. The most common distal insertion type was at the tenosynovial sheath of the long head of the biceps tendon (LHBT) in the middle humeral neck zone-this was detected in 31 of 63 patients. There were only 10 MR arthrograms biceps tendon abnormality, including 4 biceps agenesis and 6 split ruptures. CONCLUSION: A 2D and high-resolution 3D MR arthrography can demonstrate the anatomical detail around the bicipital groove and facilitate the differentiation between a biceps tendon anomaly and an AEST. On high-resolution 3D MR arthrographic images, the AEST tends to be in the anterior midline and anteromedial portions of the biceps synovium with intra-synovial, extra-synovial, and trans-synovial courses and its three different insertion types.

No Difference In Clinical Outcomes Following Repair of Large Retracted Anterior Rotator Cuff Tears Using Patch Augmentation With Human Dermal Allograft Versus Anterior Cable Reconstruction With Biceps Tendon Autograft.

PURPOSE: To compare the clinical outcomes and tendon integrity after rotator cuff repair combined with anterior cable reconstruction (ACR) using the proximal biceps tendon and patch augmentation (PA) using a human dermal allograft (HDA) in a large retracted anterior rotator cuff tear. METHODS: Patients who underwent arthroscopic rotator cuff repair with 2 different augmentation procedures between January 2017 and December 2020 were enrolled. The inclusion criteria were patients who were treated by arthroscopic rotator cuff repair with ACR using the proximal biceps tendon (ACR group) or patch augmentation using a an HDA (PA group) and follow-up for at least 2 years. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons (ASES) score, Constant score, and the number of patients who achieved minimal clinically important differences (MCID). Magnetic resonance imaging was performed to evaluate tendon integrity after surgery. RESULTS: A total of 92 patients were enrolled (ACR group = 55 patients and PA group = 37 patients). The mean ASES and Constant scores significantly improved in the ACR group (68.8 ± 15.3 and 58.4 ± 16.9 before surgery vs 91.4 ± 6.3 and 87.8 ± 6.0 after surgery, P < .001) and in the PA group (63.7 ± 16.7 and 57.9 ± 15.4 before surgery vs 93.1 ± 6.3 and 88.3 ± 6.2 after surgery, P < .001). Overall, 78 patients (84.8%) achieved the MCID with 81.8% in the ACR group and 89.2% in the PA group, with no significant differences between the 2 groups (P = .638). Ten patients (18.2%) had retear in the ACR group, and three patients (8.1%) had retear in the PA group (P = .174). CONCLUSIONS: In large retracted anterior rotator cuff tears, both augmentation techniques using biceps tendon autograft and HDA provided satisfactory clinical outcomes that achieved the MCID in 84.8%, range of motion restoration, and lower retear rates with no significant differences between the two groups. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Minimally invasive ultrasound-assisted cutting thread tenotomy of the deep digital flexor tendon in horses: An ex vivo study.

OBJECTIVE: To evaluate the feasibility and limitations associated with a minimally invasive ultrasound-assisted cutting thread technique for tenotomy of the deep digital flexor tendon (DDFT) in horses. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Twenty cadaveric forelimbs. METHODS: Forelimbs were placed on a jig to mimic a standing semiflexed position and the midmetacarpal region was prepared to perform tenotomy of the DDFT using a percutaneous technique with a cutting thread. For that purpose, the thread was placed percutaneously around the DDFT (first dorsally and then palmarly) with the aid of a curved 20 gauge spinal needle. Tendon palpation/manipulation and ultrasonographic assessment assisted thread placement. Procedure time and skin puncture size were recorded. Limbs were then dissected to evaluate the degree of DDFT transection and the presence of any iatrogenic lesions. RESULTS: The DDFT was completely transected in all cases. Minor lesions of the superficial digital flexor tendon were found in 11/20 limbs and considered clinically irrelevant. However, the neurovascular bundle was damaged in 6/20 limbs (four limbs had nerve damage and two limbs had a nerve and either a palmar artery or vein damaged). The skin puncture hole sizes ranged from undetectable to 5 mm long. The average duration of the procedure was 7 min and 38 s (range: 4 min 56 s to 10 min 19 s). CONCLUSION: A DDFT tenotomy can be performed reliably with a percutaneous cutting thread technique. However, refinement of the technique is required to minimize iatrogenic damage. CLINICAL SIGNIFICANCE: The reported technique allows a DDFT tenotomy to be performed in a minimally invasive manner and has the potential to be clinically applicable.

Biomechanical analysis of tendon regeneration capacity of Iberian ribbed newts following transection injury: Comparison to a mouse model.

Adult mammals are known for their poor ability to regenerate tissues, including tendons. On the other hand, urodeles have become an important model in regenerative studies for their remarkable ability to regenerate various body parts and organs throughout life, such as limbs, retinas, or even the brain. However, little is known about their capacity to regenerate injured tendons. If newts can also repair tendons without scar formation, they may be a suitable animal model for tendon regeneration studies in other adult vertebrates. Therefore, the present study used Iberian ribbed newts to characterize mechanical and structural regeneration of tendons following transection, using tensile tests and multiphoton microscopy. A digital flexor tendon in a hindlimb was transected either partially or completely, and regenerated tendon was examined 6 and 12 weeks after the operation. Tensile strength of regenerated tendons was significantly less than normal at 6 weeks, but was remarkably recovered at 12 weeks, reaching levels comparable to those of uninjured tendons. On the other hand, mouse tendons demonstrated poor recovery of strength even after 12 weeks. Multiphoton microscopy revealed that tendon-like collagenous tissue bridges residual tendon stubs in newts, but disorganized scar-like tissue filled the injured location in mice. These findings highlight the remarkable capacity of newts to recover from tendon injury and confirm the utility of newts as a model to study tendon regeneration.

Shear wave elastography correlates to degeneration and stiffness of the long head of the biceps tendon in patients undergoing tenodesis with arthroscopic shoulder surgery.

BACKGROUND: Tendinopathy of the long head of the biceps (LHB) tendon causes degeneration and changes its stiffness. However, a reliable means of diagnosis has not been established. Shear wave elastography (SWE) provides quantitative tissue elasticity measurements. In this study, the relationship of preoperative SWE values with biomechanically measured stiffness and degeneration of the LHB tendon tissue was investigated. METHODS: LHB tendons were obtained from 18 patients who underwent arthroscopic tenodesis. SWE values were measured preoperatively at 2 sites, proximal to and within the bicipital groove of the LHB tendon. The LHB tendons were detached immediately proximal to the fixed sites and at their superior labrum insertion. Tissue degeneration was histologically quantified using the modified Bonar score. Tendon stiffness was determined using a tensile testing machine. RESULTS: The SWE values of the LHB tendon were 502.1 ± 113.6 kPa proximal to the groove and 439.4 ± 123.3 kPa within the groove. The stiffness was 39.3 ± 19.2 N/mm. The SWE values displayed a moderate positive correlation with the stiffness proximal to the groove (r = 0.80) and within it (r = 0.72). The SWE value of the LHB tendon within the groove showed a moderate negative correlation with the modified Bonar score (r = -0.74). CONCLUSIONS: These findings suggest that preoperative SWE values of the LHB tendon correlate moderately positively with stiffness and moderately negatively with tissue degeneration. Therefore, SWE may predict LHB tendon tissue degeneration and changes in stiffness caused by tendinopathy.

Management of Patellar Tendinopathy.

Patellar tendinopathy is a common pathology typically seen in athletes involved in repetitive explosive jumping and running activities. Also known as jumpers' knee, it is commonly seen in high-level basketball players. Typically, athletes continue to play with symptoms, which can be aggravated and progress to partial patellar tendon tears. When partial patellar tendon tears occur, prolonged recovery and decreased performance is commonly seen. The pathology and treatment can be frustrating for both the athlete and medical provider. Patellar tendinopathy typically does not involve inflammation but rather microinjury to the tendon fibers, which leads to mucoid degeneration, necrosis, and loss of transitional fibrocartilage. When partial tendon tears do occur, the typical location is posteromedially adjacent to the patella. Treatment involves a stepwise approach starting with nonoperative means, including activity modification, nonsteroidal anti-inflammatories, and physical therapy focused on eccentrics. Extracorporeal shock wave treatments and injections with platelet-rich plasma or bone marrow aspirate concentrate should be considered, with evolving literature to support their use. Ultrasound percutaneous tendon scrapping with a needle supplemented with the aforementioned injections is an emerging treatment option that the authors have found to be helpful, although further studies are required. Surgical intervention is considered after failure of nonoperative treatments, and typically occurs in tears greater than 50% of the tendon thickness and in tendons with increased thickness (>8.8 mm). Open or arthroscopic debridement can be considered, with no studies showing superior outcomes with either technique; however, no high-quality comparison studies exist. The authors prefer an open technique where, much like a bone-patellar tendon-bone harvest, the unhealthy proximal tendon and bone are excised with then closure of the healthy tendon with absorbable sutures. Suture anchor repair may also be used when necessary. In a recent systematic review, surgical management of patellar tendinopathy has been shown to result in improved patient-reported outcomes with return to sport at high levels.1 Treatment for the difficult and sometimes frustrating pathology of patellar tendinopathy continues to evolve, with biologic and less-invasive ultrasound-based treatments showing promise, and surgical intervention providing reliable outcomes.

Editorial Commentary: Dasatinib With Quercetin Shows Promise in Decreasing Age-Related Senescence in the Rotator Cuff Tendon-Can It Work Elsewhere?

Cellular senescence is a fundamental mechanism seen in all age-related diseases. Human supraspinatus tendon and adjacent bursal specimens evaluated for cellular senescence by immunohistochemistry and gene expression show more senescent cells in older patients. This confirms the observation that older patients are more likely to have rotator cuff pathology, and older age is associated with lower rates of rotator cuff healing and more frequent tendon retears. Senolytic drugs can selectively eliminate senescent cells without a localized or systemic impact. Tendon and bursal specimens co-cultured and then incubated with dasatinib and quercetin for 48 hours show a significant decrease in senescent cells. This suggests that these drugs may slow biological aging in rotator cuff tendons and offer the possibility of a clinically effective treatment for the aging rotator cuff tendon. Moreover, this concept is promising for the development of future effective therapies addressing tissue senescence.

Treatment of Naturally Occurring Tendon Disease with Allogeneic Multipotent Mesenchymal Stromal Cells: A Randomized, Controlled, Triple-Blinded Pilot Study in Horses.

The treatment of tendinopathies with multipotent mesenchymal stromal cells (MSCs) is a promising option in equine and human medicine. However, conclusive clinical evidence is lacking. The purpose of this study was to gain insight into clinical treatment efficacy and to identify suitable outcome measures for larger clinical studies. Fifteen horses with early naturally occurring tendon disease were assigned to intralesional treatment with allogeneic adipose-derived MSCs suspended in serum or with serum alone through block randomization (dosage adapted to lesion size). Clinicians and horse owners remained blinded to the treatment during 12 months (seven horses per group) and 18 months (seven MSC-group and five control-group horses) of follow-up including clinical examinations and diagnostic imaging. Clinical inflammation, lameness, and ultrasonography scores improved more over time in the MSC group. The lameness score difference significantly improved in the MSC group compared with the control group after 6 months. In the MSC group, five out of the seven horses were free of re-injuries and back to training until 12 and 18 months. In the control group, three out of the seven horses were free of re-injuries until 12 months. These results suggest that MSCs are effective for the treatment of early-phase tendon disease and provide a basis for a larger controlled study.