TRIM54 alleviates inflammation and apoptosis by stabilizing YOD1 in rat tendon-derived stem cells.

Tendinopathy is a disorder of musculoskeletal system that primarily affects athletes and the elderly. Current treatment options are generally comprised of various exercise and loading programs, therapeutic modalities, and surgical interventions and are limited to pain management. This study is to understand the role of TRIM54 (tripartite motif containing 54) in tendonitis through in vitro modeling with tendon-derived stem cells (TDSCs) and in vivo using rat tendon injury model. Initially, we observed that TRIM54 overexpression in TDSCs model increased stemness and decreased apoptosis. Additionally, it rescued cells from tumor necrosis factor α-induced inflammation, migration, and tenogenic differentiation. Further, through immunoprecipitation studies, we identified that TRIM54 regulates inflammation in TDSCs by binding to and ubiquitinating YOD1. Further, overexpression of TRIM54 improved the histopathological score of tendon injury as well as the failure load, stiffness, and young modulus in vivo. These results indicated that TRIM54 played a critical role in reducing the effects of tendon injury. Consequently, these results shed light on potential therapeutic alternatives for treating tendinopathy.

Nonoperative or Surgical Treatment of Acute Achilles' Tendon Rupture.

BACKGROUND: Whether surgical repair of an acute Achilles' tendon rupture by an open-repair or minimally invasive approach is associated with better outcomes than nonsurgical treatment is not clear. METHODS: We performed a multicenter, randomized, controlled trial that compared nonoperative treatment, open repair, and minimally invasive surgery in adults with acute Achilles' tendon rupture who presented to four trial centers. The primary outcome was the change from baseline in the Achilles' tendon Total Rupture Score (scores range from 0 to 100, with higher scores indicating better health status) at 12 months. Secondary outcomes included the incidence of tendon rerupture. RESULTS: A total of 554 patients underwent randomization, and 526 patients were included in the final analysis. The mean changes in the Achilles' tendon Total Rupture Score were -17.0 points in the nonoperative group, -16.0 points in the open-repair group, and -14.7 points in the minimally invasive surgery group (P = 0.57). Pairwise comparisons provided no evidence of differences between the groups. The changes from baseline in physical performance and patient-reported physical function were similar in the three groups. The number of tendon reruptures was higher in the nonoperative group (6.2%) than in the open-repair or minimally invasive surgery group (0.6% in each). There were 9 nerve injuries in the minimally invasive surgery group (in 5.2% of the patients) as compared with 5 in the open-repair group (in 2.8%) and 1 in the nonoperative group (in 0.6%). CONCLUSIONS: In patients with Achilles' tendon rupture, surgery (open repair or minimally invasive surgery) was not associated with better outcomes than nonoperative treatment at 12 months. (Funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital; ClinicalTrials.gov number, NCT01785264.).

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.

Extracellular Vesicles From Primed Adipose-Derived Stem Cells Enhance Achilles Tendon Repair by Reducing Inflammation and Promoting Intrinsic Healing.

Achilles tendon rupture is a common sports-related injury. Even with advanced clinical treatments, many patients suffer from long-term pain and functional deficits. These unsatisfactory outcomes result primarily from an imbalanced injury response with excessive inflammation and inadequate tendon regeneration. Prior studies showed that extracellular vesicles from inflammation-primed adipose-derived stem cells (iEVs) can attenuate early tendon inflammatory response to injury. It remains to be determined if iEVs can both reduce inflammation and promote regeneration in the later phases of tendon healing and the underlying mechanism. Therefore, this study investigated the mechanistic roles of iEVs in regulating tendon injury response using a mouse Achilles tendon injury and repair model in vivo and iEV-macrophage and iEV-tendon cell coculture models in vitro. Results showed that iEVs promoted tendon anti-inflammatory gene expression and reduced mononuclear cell accumulation to the injury site in the remodeling phase of healing. iEVs also increased collagen deposition in the injury center and promoted tendon structural recovery. Accordingly, mice treated with iEVs showed less peritendinous scar formation, much lower incidence of postoperative tendon gap or rupture, and faster functional recovery compared to untreated mice. Further in vitro studies revealed that iEVs both inhibited macrophage M1 polarization and increased tendon cell proliferation and collagen production. The iEV effects were partially mediated by miR-147-3p, which blocked the toll-like receptor 4/NF-κB signaling pathway that activated the M1 phenotype of macrophages. The combined results demonstrate that iEVs are a promising therapeutic agent that can enhance tendon repair by attenuating inflammation and promoting intrinsic healing.

Effect of cilostazol on healing of achilles tendon ruptures: an experimental study on rats.

PURPOSE: This study aimed to evaluate whether cilostazol (phosphodiesterase III inhibitor) could enhance the healing of Achilles tendon ruptures in rats. MATERIALS AND METHODS: The Achilles tendons of 24 healthy male adult rats were incised and repaired. The rats were randomly allocated to cilostazol and control groups. The cilostazol group received daily intragastric administration of 50 mg/kg cilostazol for 28 days, while the control group did not receive any medication. The rats were sacrificed on the 30th day, and the Achilles tendon was evaluated for biomechanical properties, histopathological characteristics, and immunohistochemical analysis. RESULTS: All rats completed the experiment. The Movin sum score of the control group was significantly higher (p = 0.008) than that of the cilostazol group, with means of 11 ± 0.63 and 7.50 ± 1.15, respectively. Similarly, the mean Bonar score was significantly higher (p = 0.026) in the control group compared to the cilostazol group (8.33 ± 1.50 vs. 5.5 ± 0.54, respectively). Moreover, the Type I/Type III Collagen ratio was notably higher (p = 0.016) in the cilostazol group (52.2 ± 8.4) than in the control group (34.6 ± 10.2). The load to failure was substantially higher in the cilostazol group than in the control group (p = 0.034), suggesting that the tendons in the cilostazol group were stronger and exhibited greater resistance to failure. CONCLUSIONS: The results of this study suggest that cilostazol treatment significantly improves the biomechanical and histopathological parameters of the healing Achilles tendon in rats. Cilostazol might be a valuable supplementary therapy in treating Achilles tendon ruptures in humans. Additional clinical studies are, however, required to verify these outcomes.

Diagnostic performance of long head of biceps tendon tears on MRI: systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to determine the diagnostic performance of conventional MRI and MR arthrography for tendinosis, and partial and complete tears of the long head of the biceps tendon (LHBT) using arthroscopy as the reference standard. MATERIALS AND METHODS: A systematic review was performed using predefined data fields in PubMed, and all articles published from January 2000 up to April 2022 were retrospectively pooled and reviewed. Six MRI studies on complete tear (n = 555) and ten studies on partial tear/tendinosis (n = 2487) were included in the analysis. Two of the included studies in each group investigated the use of MR arthrography. The data sets were analyzed using a univariate approach with the DerSimonian and Laird random effects model and the proportional hazards model. RESULTS: MRI shows high specificities in diagnosing complete tears of the LHBT ranging from 93.0 to 99.0%. Diagnostic sensitivity was more heterogeneous ranging from 55.9 to 90.0%. The overall negative likelihood ratio was 0.29 (95% CI: 0.17-0.50) and the overall positive likelihood ratio was 37.3 (95% CI: 11.9-117.4). The mean sensitivity in diagnosing partial tear/tendinosis of the LHBT was 67.8% (95% CI: 54.3-78.9%) and the specificity was 75.9% (95% CI: 63.6-85.0%), resulting in a balanced accuracy of 71.9%. The overall negative likelihood ratio was 0.44 (95% CI: 0.32-0.59) and the overall positive likelihood ratio was 2.64 (95% CI: 1.91-3.65). CONCLUSION: MRI is highly specific for the diagnosis of complete tears of the LHBT, whereas diagnostic sensitivity was more heterogeneous. The diagnosis of partial tears and/or tendinosis of the LHBT remains challenging on MRI, which may warrant complementary clinical examination or other imaging modalities to increase diagnostic confidence in equivocal cases. CLINICAL RELEVANCE STATEMENT: Conventional MRI and MR arthrography have high diagnostic performance for complete tendon tear when compared to arthroscopy. The diagnosis of tendinosis/partial tears remains challenging and may require comparison with clinical tests and other imaging modalities. KEY POINTS: •There is no clear consensus regarding the primary imaging modality for the evaluation of LHBT disorders. •Conventional MRI and MR arthrography are highly specific in diagnosing complete tears of the LHBT. •Diagnosis of partial tears/tendinosis of the LHBT on conventional MRI and MR arthrography remains a diagnostic challenge.

Local and Systemic Side Effects of Corticosteroid Injections for Musculoskeletal Indications.

Corticosteroid injections can be associated with a range of potential side effects, which may be classified as local or systemic and further stratified as immediate or delayed in onset. Radiologists performing image-guided musculoskeletal injections should recognize the potential side effects of corticosteroid medication when counseling patients before injection and consider such side effects in planning individual injections. This Review summarizes the available evidence regarding the local and systemic side effects of corticosteroid injections performed for musculoskeletal indications. Local side effects include postinjection flare, skin hypopigmentation and atrophy, infection, tendon rupture, accelerated progression of osteoarthritis, and osseous injury. Systemic side effects include adrenal suppression or insufficiency, facial flushing, hypertension, hyperglycemia, and osteoporosis. Additional targeted counseling is warranted regarding side effects that are specific to certain patient populations (i.e., premenopausal women, patients with diabetes, athletes, and pediatric patients). Corticosteroid injections are contraindicated in the presence of superficial or deep infection, fracture, or a prosthetic joint. Guidelines on the frequency, duration, and maximal lifetime use of corticosteroid injections are currently lacking. Further research is needed regarding the long-term complications of continuous corticosteroid use, particularly with regard to osseous effects.

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.

Adaptive responses of skeletal muscle to calcaneal tendon partial injury in rats: insights into remodeling and plasticity.

BACKGROUND: Skeletal muscle is a highly adaptive tissue, capable of responding to different physiological and functional demands, even in situations that may cause instability. OBJECTIVES: To evaluate how partial calcaneal tendon (CT) injuries affect the remodeling and plasticity of the gastrocnemius muscle over time. METHODS AND RESULTS: The study was carried out with Wistar rats randomly divided into five groups. The control group comprised animals not subjected to partial CT damage. The remaining four groups were subjected to partial CT damage and were further categorized based on the time of euthanasia: 3, 14, 28, and 55 days after injury. The gastrocnemius muscle was collected and used for gene expression analysis, zymography, flow cytometry, and morphology. The calcaneal tendon was analyzed only to verify the presence of the partial injury. RESULTS: The impact of partial CT injury on the gastrocnemius homeostasis, particularly on gene expression, was more pronounced in the 3-day group compared to the other groups, especially the control group. Cytokine profile and morphologic alterations occurred in the 55 days group when compared to the other groups. CONCLUSIONS: The data reported here suggest that partial injury can negatively affect intracellular signaling and degradation pathways, disturbing the muscular extracellular matrix regulatory mechanisms and communication with the tendon. However, skeletal muscle seems to mitigate these harmful effects in comparison with lesions that affect muscle and tendon.

Flexed elbow, abducted shoulder, forearm supinated (FABS) reconstruction from three-dimensional elbow MRI: diagnostic performance assessment in biceps head anatomy and pathology.

AIM: To determine inter-reader analysis and diagnostic performance on digitally reconstructed virtual flexed, abducted, supinated (FABS) imaging from three-dimensional (3D) isotropic elbow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Six musculoskeletal radiologists independently evaluated elbow MRI images with virtual FABS reconstructions, blinded to clinical findings and final diagnoses. Each radiologist recorded a binary result as to whether the tendon was intact and if both heads were visible, along with a categorical value to the type of tear and extent of retraction in centimetres where applicable. Kappa and interclass correlation (ICC) were reported with 95% confidence intervals. Areas under the receiver operating curve (AUC) were reported. RESULTS: FABS reconstructions were obtained successfully in all 48 cases. With respect to tendon intactness, visibility of both heads, and type of tear, the Kappa values were 0.66 (0.53-0.78), 0.24 (0.12-0.37), and 0.55 (0.43-0.66), respectively. For the extent of retraction, the ICC was 0.85 (0.79-0.91) when including the tendons with and without retraction and 0.78 (0.61-0.91) when only including tendons with retraction. For tear versus no tear, AUC values were 0.82 (0.74-0.89) to 0.96 (0.91-1.01). CONCLUSION: Digital reconstruction of FABS positioning is feasible and allows good assessment of individual tendon head tears and retraction with high diagnostic performance.

Endothelial cells-derived exosomes-based hydrogel improved tendinous repair via anti-inflammatory and tissue regeneration-promoting properties.

Tendon injuries are common orthopedic ailments with a challenging healing trajectory, especially in cases like the Achilles tendon afflictions. The healing trajectory of tendon injuries is often suboptimal, leading to scar formation and functional impairment due to the inherent low metabolic activity and vascularization of tendon tissue. As pressing is needed for effective interventions, efforts are made to explore biomaterials to augment tendon healing. However, tissue engineering approaches face hurdles in optimizing tissue scaffolds and nanomedical strategies. To navigate these challenges, an injectable hydrogel amalgamated with human umbilical vein endothelial cells-derived exosomes (HUVECs-Exos) was prepared and named H-Exos-gel in this study, aiming to enhance tendon repair. In our research involving a model of Achilles tendon injuries in 60 rats, we investigated the efficacy of H-Exos-gel through histological assessments performed at 2 and 4 weeks and behavioral assessments conducted at the 4-week mark revealed its ability to enhance the Achilles tendon's mechanical strength, regulate inflammation and facilitate tendon regeneration and functional recovery. Mechanically, the H-Exos-gel modulated the cellular behaviors of macrophages and tendon-derived stem cells (TDSCs) by inhibiting inflammation-related pathways and promoting proliferation-related pathways. Our findings delineate that the H-Exos-gel epitomizes a viable bioactive medium for tendon healing, heralding a promising avenue for the clinical amelioration of tendon injuries.

Early Predictors of Recovery From Nonoperatively Treated Achilles Tendon Rupture: 1 Year Follow-Up Study.

PURPOSE: To investigate early structural and mechanical predictors of plantarflexor muscle strength and the magnitude of Achilles tendon (AT) nonuniform displacement at 6 and 12 months after AT rupture. METHODS: Thirty-five participants (28 males and 7 females; mean ± SD age 41.7 ± 11.1 years) were assessed for isometric plantarflexion maximal voluntary contraction (MVC) and AT nonuniformity at 6 and 12 months after rupture. Structural and mechanical AT and plantarflexor muscle properties were measured at 2 months. Limb asymmetry index (LSI) was calculated for all variables. Multiple linear regression was used with the 6 and 12 month MVC LSI and 12 month AT nonuniformity LSI as dependent variables and AT and plantarflexor muscle properties at 2 months as independent variables. The level of pre- and post-injury sports participation was inquired using Tegner score at 2 and 12 months (scale 0-10, 10 = best possible score). Subjective perception of recovery was assessed with Achilles tendon total rupture score (ATRS) at 12 months (scale 0-100, 100=best possible score). RESULTS: Achilles tendon resting angle (ATRA) symmetry at 2 months predicted MVC symmetry at 6 and 12 months after rupture (ß = 2.530, 95% CI 1.041-4.018, adjusted R2 = 0.416, p = 0.002; ß = 1.659, 95% CI 0.330-2.988, adjusted R2 = 0.418, p = 0.016, respectively). At 12 months, participants had recovered their pre-injury level of sports participation (Tegner 6 ± 2 points). The median (IQR) ATRS score was 92 (7) points at 12 months. CONCLUSION: Greater asymmetry of ATRA in the early recovery phase may be a predictor of plantarflexor muscle strength deficits up to 1 year after rupture. TRIAL REGISTRATION: This research is a part of "nonoperative treatment of Achilles tendon rupture in Central Finland: a prospective cohort study" that has been registered in ClinicalTrials.gov (NCT03704532).

Personalized tendon loading reduces muscle-tendon imbalances in male adolescent elite athletes.

An imbalanced adaptation of muscle strength and tendon stiffness in response to training may increase tendon strain (i.e., the mechanical demand on the tendon) and consequently tendon injury risk. This study investigated if personalized tendon loading inducing tendon strain within the effective range for adaptation (4.5%-6.5%) can reduce musculotendinous imbalances in male adolescent handball athletes (15-16 years). At four measurement time points during a competitive season, we assessed knee extensor muscle strength and patellar tendon mechanical properties using dynamometry and ultrasonography and estimated the tendon's structural integrity with a peak spatial frequency (PSF) analysis of proximal tendon ultrasound scans. A control group (n = 13) followed their usual training routine, an intervention group (n = 13) integrated tendon exercises into their training (3x/week for ~31 weeks) with a personalized intensity corresponding to an average of ~6.2% tendon strain. We found a significant time by group interaction (p < 0.005) for knee extensor muscle strength and normalized patellar tendon stiffness with significant increases over time only in the intervention group (p < 0.001). There were no group differences or time-dependent changes in patellar tendon strain during maximum voluntary contractions or PSF. At the individual level, the intervention group demonstrated lower fluctuations of maximum patellar tendon strain during the season (p = 0.005) and a descriptively lower frequency of athletes with high-level tendon strain (≥9%). The findings suggest that the personalized tendon loading program reduced muscle-tendon imbalances in male adolescent athletes, which may provide new opportunities for tendon injury prevention.

Tendon Aging.

Tendons are mechanosensitive connective tissues responsible for the connection between muscles and bones by transmitting forces that allow the movement of the body, yet, with advancing age, tendons become more prone to degeneration followed by injuries. Tendon diseases are one of the main causes of incapacity worldwide, leading to changes in tendon composition, structure, and biomechanical properties, as well as a decline in regenerative potential. There is still a great lack of knowledge regarding tendon cellular and molecular biology, interplay between biochemistry and biomechanics, and the complex pathomechanisms involved in tendon diseases. Consequently, this reflects a huge need for basic and clinical research to better elucidate the nature of healthy tendon tissue and also tendon aging process and associated diseases. This chapter concisely describes the effects that the aging process has on tendons at the tissue, cellular, and molecular levels and briefly reviews potential biological predictors of tendon aging. Recent research findings that are herein reviewed and discussed might contribute to the development of precision tendon therapies targeting the elderly population.

Aged Tendons Exhibit Altered Mechanisms of Strain-Dependent Extracellular Matrix Remodeling.

Aging is a primary risk factor for degenerative tendon injuries, yet the etiology and progression of this degeneration are poorly understood. While aged tendons have innate cellular differences that support a reduced ability to maintain mechanical tissue homeostasis, the response of aged tendons to altered levels of mechanical loading has not yet been studied. To address this question, we subjected young and aged murine flexor tendon explants to various levels of in vitro tensile strain. We first compared the effect of static and cyclic strain on matrix remodeling in young tendons, finding that cyclic strain is optimal for studying remodeling in vitro. We then investigated the remodeling response of young and aged tendon explants after 7 days of varied mechanical stimulus (stress deprivation, 1%, 3%, 5%, or 7% cyclic strain) via assessment of tissue composition, biosynthetic capacity, and degradation profiles. We hypothesized that aged tendons would show muted adaptive responses to changes in tensile strain and exhibit a shifted mechanical setpoint, at which the remodeling balance is optimal. Interestingly, we found that 1% cyclic strain best maintains native physiology while promoting extracellular matrix (ECM) turnover for both age groups. However, aged tendons display fewer strain-dependent changes, suggesting a reduced ability to adapt to altered levels of mechanical loading. This work has a significant impact on understanding the regulation of tissue homeostasis in aged tendons, which can inform clinical rehabilitation strategies for treating elderly patients.

Ultrasound-guided Hydrogel Injection Provides Better Therapeutic Effects After Hand Tendon Surgery Than Intraoperative Injection: A Randomized Controlled Trial.

BACKGROUND: Hydrogels are used to provide a barrier against peritendinous adhesion formation, but when implanted intraoperatively, they degrade rapidly and aggravate early inflammatory pain. It is uncertain whether clinical efficacy can be improved by avoiding the inflammatory phase when hydrogels are delivered during adhesion formation. QUESTIONS/PURPOSES: (1) Compared with intraoperative hydrogel application, does ultrasound-guided postoperative application result in better total active motion (TAM) at 12 months after tendon injury? (2) Does ultrasound-guided postoperative application of hydrogels result in lower pain, better function, and better satisfaction? METHODS: This open-label, prospective, single-center, randomized controlled trial was conducted by reparative and reconstructive surgeons at the National Orthopedics Clinical Medical Center, Shanghai, People's Republic of China. Between May 2021 and December 2022, 53% (168 of 317) of patients who met our inclusion criteria were recruited, and 47% (149 of 317) of patients were excluded because of the exclusion criteria. Finally, 84 patients were randomized to the postoperative group to receive ultrasound-guided carboxymethyl chitosan (CMC) hydrogel delayed injection, and 84 patients were randomized to the intraoperative group to receive CMC hydrogel intraoperative application. Another 8% (7 of 84) of patients in the postoperative group and 10% (8 of 84) of patients in the intraoperative group were lost before the minimum study follow-up time of 1 year or had incomplete datasets, leaving 91% (153 of 168) of patients with data for analysis. Data on outcome events were analyzed according to the intention-to-treat principle, which included all patients who underwent randomization. Follow-up visits were completed at 3 weeks, 6 weeks, 3 months, 6 months, and 12 months after tendon repair. The primary outcome was TAM (ie, the sum of the degrees of active metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint flexion less the degrees from full extension; minimum clinically important difference [MCID] 20°) at 12 months. Secondary outcomes included pain (measured with a VAS; range 0 to 10, a higher score indicating worse pain; MCID 0.6), Michigan Hand Outcomes Questionnaire activities of daily living (MHQ-ADL) score (range 0 to 100, a higher score indicating better outcomes; MCID 10.1), and MHQ satisfaction (MHQ-SAT) score (range 0 to 100, a higher score indicating better outcomes; MCID 33.0). RESULTS: At 12 months, the ultrasound-guided postoperative injection group had improved TAM (intraoperative 189° [95% CI 179° to 199°] versus postoperative 209° [95% CI 199° to 219°], mean difference 20° [95% CI 6° to 35°]; p = 0.006; the mean difference in the primary outcome fulfilled the MCID value at all time points). At 6 weeks, we found no clinically important difference in VAS pain scores among groups (intraoperative mean ± SD 2.0 ± 1.0 versus postoperative 1.7 ± 1.0, mean difference 0.3 [95% CI 0.1 to 0.7]; p = 0.02); however, at 3 weeks, the VAS pain scores showed clinically important difference among groups (3.6 ± 1.4 versus 2.9 ± 1.2, mean difference 0.7 [95% CI 0.3 to 1.1]; p = 0.001). At 3 months, the ultrasound-guided postoperative injection group had higher MHQ-ADL scores (intraoperative 62 ± 10 versus postoperative 75 ± 10, mean difference 13 [95% CI 11 to 17]; p < 0.001), and the mean difference of MHQ-ADL scores reached the MCID value at all time points. At 3 months, there was no clinically important difference in MHQ-SAT scores between groups (intraoperative 62 ± 8 versus postoperative 70 ± 8, mean difference 8 [95% CI 6 to 11]; p < 0.001). CONCLUSION: Compared with intraoperative CMC hydrogel injection, postoperative ultrasound-guided injection improved the TAM and function of the affected limb, showed a short-term pain control effect, and did not increase the risk of complications. Clinical trials are needed to confirm the safety and efficacy of ultrasound-guided postoperative injection of CMC hydrogels and to determine the most effective dose and the health and economic benefits of treatment. LEVEL OF EVIDENCE: Level I, therapeutic study.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm 2 versus 256 ± 43 /mm 2 , mean difference 188 /mm 2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m 2 versus 8 ± 4 kJ/m 2 , mean difference 8 kJ/m 2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

Effectiveness of a novel finger range-of-motion brace for extensor tendon injury: a report of 10 patients.

BACKGROUND: Extensor tendon injuries require surgical repair, followed by rehabilitation to ensure optimal outcomes. Immobilization has been the cornerstone of postoperative management. However, immobilization after surgery frequently makes the finger stiffness, often resulting in reduced functionality and quality of life for patients. Recent studies indicate that early controlled motion can significantly improve outcomes, but safe early range of motion (ROM) exercise is a significant clinical challenge. This article aims to check the efficacy of the novel designed finger ROM brace for preventing finger stiffness for extensor tendon injuries with case series. METHODS: A finger ROM brace was designed based on the natural finger movement. Like a real finger, there are two tiny hinge joints and three round-shape body components. The design aimed to be ergonomic dynamic splint assisting controlled motion to promote early motion, thus reducing tendon tension and preventing stiffness. Elastic resistant ROM exercise could be by inserting a silicone band into the groove on the components and free movement could be achieved by removing a silicone band. RESULT: Between December 2022 and July 2023, 10 patients who underwent tenorrhaphy because of extensor tendon laceration were involved. Complete extensor tendon laceration was 3 patients, other seven patients had partial laceration of extensor tendons. Surgery was performed within 2 days of injury, and no infection was observed in all patients. After the extensor tendon was confirmed as healed state by ultrasound, the patients were permit the active exercise wearing finger ROM brace with a silicone band. Within 1-2 weeks after elastic resistant exercise, the patients could achieve free full ROM movement without any complication. CONCLUSION: The novel finger ROM brace combines the advantages of dynamic splinting and under-actuated mechanisms to offer a comprehensive solution for preventing stiffness after extensor tendon suture. Future studies should focus on clinical trials to validate the efficacy and safety of this brace in a larger population.

Injury of flexor halluics longus tendon in amateur marathon runners results in abnormal plantar pressure distribution: observational study.

OBJECTIVE: To analyze the changes of plantar pressure in amateur marathon runners with flexor halluics longus (FHL) tendon injury using the Medtrack-Gait plantar pressure measurement system, and to explore whether the plantar pressure data can be used as an index for the diagnosis of injury. METHODS: A total of 39 healthy amateur marathon runners without any ankle joint symptoms were recruited. Dynamic and static plantar pressure data were measured using the pressure plate of Medtrack-Gait. According to MRI imaging findings, whether the FHL tendon was injured or not was judged, and the dynamic and static data were divided into the injury group and control group. The data with statistically significant differences between the two groups were used to make the receiver operating characteristic (ROC) curve. RESULT: The maximum contact area (PA) of the first metatarsal(M1) region, the maximum load-bearing peak value (PW) and the time pressure integral (PMPTI) of the second metatarsal(M2) region in the injury group were lower than those in the control group, respectively (P < 0.05). The maximum contact area (PA) of the fifth metatarsal(M5) region was higher than that in the control group (P < 0.05). The area under curve (AUC) value of the ROC curve of the PA of M1 region, the PW and PMPTI of M2 region were statistically (P < 0.05). CONCLUSION: FHL tendon injury resulted in decreased PA in M1, decreased PW and PMPTI in M2, and increased PA in the M5 region, suggesting that FHL tendon injury resulted in a force shift from the medial to the lateral side of the foot. The PA of M1, PW and PMPTI of M2 have certain diagnostic value for early FHL injury in amateur marathon runners.

Effect of a single versus serial platelet-rich plasma injection on the healing of acute patellar tendon defect: an experimental study.

BACKGROUND: There is no consensus on the frequency and timing of platelet-rich plasma (PRP) injection in tendon healing. We aimed to evaluate the effectiveness of single versus multiple PRP injections in the healing of patellar tendon defects in the experimental model, through histological and biomechanical investigation. METHODS: Forty-four male skeletally mature Dutch rabbits were randomly divided into the five study groups ( A, B,C, D,E). After creating a longitudinal acute patellar tendon defect on both knees (One-third the width of the patella tendon), the right legs of the rabbits were used as the intervention group and the left legs as the control groups. Animals in groups A, B, and C were euthanized on days 7, 14, and 28, respectively, after the first PRP injection. Animals in group D received the second PRP injection on day 10 and was euthanized on day 14. Animals in group D received the second and third PRP injections on days 10 and 20, respectively, and were euthanized on day 28. The outcomes were evaluated histologically (modification of Movin's Grading) and biomechanically. RESULTS: The inflammatory condition was exaggerated in groups D and E. Load at failure was higher in the non-injected side of groups D and E, while there was no significant difference between the right and left legs of the three groups A, B and C. In other word, groups with a single PRP injection were more resistant to the increasing load compared to the groups with multiple PRP injections. CONCLUSIONS: PRP improves tendon healing if injected early after injury, while its injection after the initial phase of injury hampers tendon healing. In addition, a single PRP injection seems to be more effective than multiple PRP injection. Therefore, in cases where PRP injection is indicated for tendon repair, such as acute tendon injury, we recommend using a single PRP injection during tendon repair surgery.