Injured Tendons Research Articles

Current understanding of the diagnosis and management of the tendinopathy: An update from the lab to the clinical practice

Tendinopathy is labeled by many authors as a troublesome, common pathology, present in up to 30% medical care consultations involving musculoskeletal conditions. Despite the lasting interest for addressing tendon pathology, current researchers agree that even the exact definition of the term tendinopathy is unclear. Tendinopathy is currently diagnosed as a clinical hypothesis based on the patient symptoms and physical context. One of the main goals of current clinical management is to personalize treatment approaches to adapt them to the many different needs of the population.Tendons are complex structures that unite muscles and bones with two main objectives: to transmit forces and storage and release energy. Regarding the tensile properties of the tendons, several authors argued that tendons have higher tensile strength compared with muscles, however, are considered less flexible.Tendinopathy is an accepted term which is used to indicated a variety of tissue conditions that appear in injured tendons and describes a non-rupture damage in the tendon or paratendon, which is intensified with mechanical loading Even when the pathoetiology of tendinopathy is unclear, there is a wide array of treatments available to treat and manage tendinopathy. Although tendinitis usually debuts with an inflammatory response, the majority of chronic tendinopathies do not present inflammation and so the choosing of treatment should vary depending on severity, compliance, pain and duration of symptoms.The purpose of this article is to review and provide an overview about the currently research of the tendon diagnosis, management and etiology.

Novel insights into the pathogenesis of tendon injury: mechanotransduction and neuroplasticity.

Novel insights into the pathogenesis of tendon injury: mechanotransduction and neuroplasticity.

Comparison of low-level laser and dimethyl sulfoxide applications for the treatment oftendon injury in rabbits

The aim of this study was to investigate and compare the effects of low-level laser therapy (LLLT) and dimethyl sulfoxide (DMSO) on tendon healing in rabbits. A total of 30 adult healthy New Zealand rabbits were used for this study. The rabbits were randomly allocated into 3 groups containing an equal animal number. The experimental tenotomy of the Achilles tendons was created on longitudinal aspect with 10 mm in length. During the postoperative 21-day of period, rabbits in Group I were exposed to laser beam at a rate of 10.8 J/cm$^{2}$ in 5 cm$^{2}$ area for 4 min. In the same period, 30% DMSO solution was applied externally to the injured tendon region for Group II. Saline solution was applied to the injured tendons area for Group III. Daily clinical examinations of each rabbit were recorded during the treatment period. At the end of the 21-day treatment period, all rabbits were euthanized and their tendons were examined macroscopically. Histopathological examination of the tendons was then carried out. Immature and mature connective tissue cells had an equal number of distribution in Group I; mild immature connective tissue cells and mostly mature connective tissue cells were observed in Group II, and partially longitudinal, scattered, and irregularly arranged, immature connective tissue cells (fibroblasts) were observed in Group III. As a result, satisfactory findings were obtained from LLLT and DMSO applications for the treatment of tendon injuries taking into consideration the histopathological and clinical findings. Moreover, DMSO provided a better recovery when these two applications were compared. However, it was suggested that combined application of DMSO and LLLT might have a strong positive effect on the healing process.

Design and In Vivo Testing of Novel Single-Stage Tendon Graft Using Polyurethane Nanocomposite Polymer for Tendon Reconstruction

Severe trauma, failure of prior surgical repair, delayed presentation and excessive scarring around the flexor tendon bed often necessitate a two-stage surgical reconstruction, where a silicone spacer is used in the first stage to recreate the fibro-osseous tunnel through which the tendon graft can glide in the second stage. This staged procedure involves great commitment on the part of both patient and surgeon, over the course of several months, involving a prolonged period of rehabilitation that can be quite disruptive to the patient's life and work. Reducing this from a two-stage into a single-stage procedure, therefore, has the potential to reduce rehabilitation time and cost, expedite return to work, and improve outcomes. To address this, we developed polyurethane (PU) nanocomposite, as an engineered tendon sheath, for treatment of delayed flexor tendon division as a single-stage procedure. The clinically conformant tubular grafts were tested for their efficacy in the peroneus tertius tendon of 6 Mule sheep for 3 months. Semi-quantitative histological assessment was carried out by analysing four descriptive layers: tendon, tendon/polymer sheath interface, polymer sheath, and polymer sheath/surrounding tissue. Four (out of 6) of the implanted PU nanocomposites showed moderate to substantial healing of the injured tendons, with minimal adhesion after repair, ensuring good gliding movement. No statistical differences were observed in tendon repair based on intra-regional variation in the explanted grafts, indicating homogeneity in tendon repair. Overall, the PU nanocomposite bears morphological stability and functionality for tendon repair, in single-stage surgical reconstruction, demonstrating promising evidence for clinical translation.

Cell autonomous TGFβ signaling is essential for stem/progenitor cell recruitment into degenerative tendons.

SummaryUnderstanding cell recruitment in damaged tendons is critical for improvements in regenerative therapy. We recently reported that targeted disruption of transforming growth factor beta (TGFβ) type II receptor in the tendon cell lineage (Tgfbr2ScxCre) resulted in resident tenocyte dedifferentiation and tendon deterioration in postnatal stages. Here we extend the analysis and identify direct recruitment of stem/progenitor cells into the degenerative mutant tendons. Cre-mediated lineage tracing indicates that these cells are not derived from tendon-ensheathing tissues or from a Scleraxis-expressing lineage, and they turned on tendon markers only upon entering the mutant tendons. Through immunohistochemistry and inducible gene deletion, we further find that the recruited cells originated from a Sox9-expressing lineage and their recruitment was dependent on cell autonomous TGFβ signaling. The cells identified in this study thus differ from previous reports of cell recruitment into injured tendons and suggest a critical role for TGFβ signaling in cell recruitment, providing insights that may support improvements in tendon repair.

Patellar Tendon Structural Adaptations Occur during Pre-Season and First Competitive Cycle in Male Professional Handball Players

Background: While there is evidence that tendon adapts to training load, structural alterations in the patellar tendon in response to training loads are still unclear. The aim of this study is to identify changes in patellar tendon structure throughout pre-season and after finalizing the first competitive cycle. Methods: Nineteen professional handball players participated in the aforesaid cross-sectional study, in which patellar tendon scan and counter movement jump (CMJ) performance were conducted. Measurements were taken on the first and last day of pre-season training, and at the end of the first competitive cycle. Results: The results revealed that variation on the tendon structure occurred, mainly at the end of pre-season training; for injured tendons this occurred at the proximal (Right p = 0.02), distal (Right p = 0.01), and (Left p = 0.02) tendon, while changes in healthy tendons occurred at the mid (Left p = 0.01) and distal tendon (Right p = 0.01). At the end of the first competitive cycle, changes were observed in the distal injured tendon (p = 0.02). Conclusion: Patellar tendon shows greater structural change after completing pre-season training than at the end of the first competitive cycle, from which it may be inferred that gradual loading during pre-season training allows the tendon to adapt and potentially decrease the onset of patellar tendinopathy.

Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

Superior capsule reconstruction: anatomy, biomechanics, indications, and graft treatment.

Superior capsule reconstruction: anatomy, biomechanics, indications, and graft treatment.

Экспериментальное исследование механических свойств ахиллова сухожилия кроликов в процессе его восстановления после травмы

Актуальность. Проблема лечения больных с повреждениями сухожилий остается нерешенной. Неудовлетворительные результаты после хирургического лечения, по данным разных авторов, составляют от 15 до 62 %. Функциональный результат после хирургического восстановления поврежденных сухожилий трудно прогнозировать из-за высокого риска образования рубцового блока, препятствующего их свободному скольжению. Спайки нарушают растяжимость сухожилий, что, в свою очередь, сказывается на их прочности. Цель: исследовать в эксперименте прочностные свойства ахилловых сухожилий после их хирургического восстановления с дальнейшим использованием различных медикаментозных препаратов. Материалы и методы. Проведены исследования механических свойств ахилловых сухожилий кроликов, на которых была создана модель их частичного повреждения путем пересечения на 1/2 диаметра. Травмированное сухожилие ушивалось сухожильным швом. В ходе эксперимента изучали 5 групп препаратов ахилловых сухожилий кроликов с пяточной костью по 3 препарата в каждой группе. 1-я группа — контрольная. После выполнения сухожильного шва рану ушивали. Во 2-й группе животным вокруг сухожильного шва вводили препарат нолтрекс. В 3-й группе вводили препарат гиалуроновой кислоты, в 4-й — препарат лидазы. 5-я группа — норма, препараты неоперированных ахилловых сухожилий интактных животных. Все животные были выведены из эксперимента на 60-е сутки. По результатам испытаний рассчитывали величину модуля упругости и предел прочности препарата. Результаты. Наибольшее удлинение под действием растягивающей нагрузки величиной 30 Н было достигнуто на препаратах неоперированных ахилловых сухожилий кроликов — 2,96 ± 0,22 мм. Наименьшая величина удлинения была получена на препаратах контрольной группы — 0,83 ± 0,37 мм. Остальные группы препаратов показали промежуточные значения. Наибольшим значением модуля упругости обладают препараты ахиллова сухожилия кроликов контрольной группы — 0,216 ± 0,123 МПа. Наименьшее значение модуля упругости выявлено при изучении нетравмированных препаратов ахиллова сухожилия — 0,051 ± 0,004 МПа. Наибольшей прочностью обладали препараты контрольной группы (величина предельно допустимой нагрузки 81,81 ± 0,34 Н). Наименьшую прочность продемонстрировали препараты нетравмированных ахилловых сухожилий кроликов (величина предельно допустимой нагрузки 69,72 ± 0,18 Н). Выводы. В процессе восстановления ахиллова сухожилия кроликов после травмы наблюдается увеличение значений показателей, характеризующих прочностные свойства тканей, — модуля упругости, предельно допустимой нагрузки и предела прочности. Величина показателей, характеризующих пластические свойства тканей, уменьшается, что может стать одной из причин развития посттравматических контрактур. Наилучшие показатели с точки зрения пластичности тканей наблюдались в группе препаратов ахиллова сухожилия кроликов, леченных с помощью гиалуроновой кислоты. Наихудшие — в контрольной группе.

Morphological changes of macrophages and their potential contribution to tendon healing

Poor healing ability and adhesion formation greatly hinder the recovery of injured tendon function. Previously, our local sustained gene delivery system by using cyclooxygenases (COX-1 and COX-2)-engineered miRNA plasmid/nanoparticles loaded hydrogel significantly inhibited adhesion formation and promoted tendon healing. The present study aims to study morphological changes of the macrophages in the healing tendons after above treatment with the hydrogel. Firstly, we assessed the therapeutic effect of localized delivery of the hydrogel on cyclooxygenases in the injured rat Achilles tendon model. We found ultimate strengths of the healing tendons were significantly increased at week 2 and 3. We then studied the distribution of macrophages before and after tendon injury, and found macrophages were rapidly recruited into injured sites of tendons. After being isolated and cultured, macrophages were transfected with 6-Carboxyfluorescein (FAM) labeled siRNA/nanoparticles and presented a high transfection efficiency (>70%). We further compared the change of iNOS/CD206 in macrophages between negative control siRNA/nanoparticle group and COX siRNA/nanoparticle group. The major finding is that the morphology of the macrophages changed from type I macrophages to type II macrophages after transfection of COX siRNA/nanoparticles in vitro. Subsequently, rat Achilles tendon cells were cultured with supernatant collected from macrophages transfected with negative control siRNA/nanoparticles and COX siRNA/nanoparticles, and the proliferation of tendon cells was significantly increased in COX siRNA/nanoparticle supernatant group. Because type II macrophages are responsible for tissue repair, the changes in macrophage polarization from M1 to M2 may be one of the important events in promoting the tendon healing.

TGF-\u03b23 regulates adhesion formation through the JNK/c-Jun pathway during flexor tendon healing

BackgroundThe injured flexor tendon has poor healing ability, which is easy to cause tendon adhesion. It can affect the recovery of tendon function, which is still a long-term and difficult task for surgeons. Transforming growth factor β (TGF-β) has been widely considered to play an important role in flexor tendon repair in recent years.AimThis work was to investigate the anti-adhesion and anti-inflammatory effects of TGF-β3 on flexor digitorum longus (FDL) tendon repair rats.MethodAnastomosis models of tendon laceration in the flexion toes of rats were delivered with no treatment, vehicle, or TGF-β3 -overexpressed adenovirus vector (ad-TGF-β3) locally to the injured tendon area from day 3 to 8. Subsequently, the expression of TGF-β3, TGF-β1/2, Smad3, Smad7, JNK, phosphorylation (p)-JNK, c-Jun, and phosphorylation (p)-c-Jun were detected by western blot, the expression of Mmp9 and Mmp2 by RT-qPCR, the Range of motion (ROM) and gliding resistance by adhesion formation testing, the mechanical strength of tendon healing by biomechanical testing, the pathologic changes of flexor tendon tissues by HE staining, the expression of collagen type III by immunohistochemical staining, and the levels of IL-6, TNF-α, COX2 and IL-1β in serum by ELISA, respectively.ResultsRat models treated with no treatment showed a lower elevation of TGF-β3 and Smad7 expression, and a higher elevation of TGF-β1/2 and Smad3 expression, during day 14 to day 28. Besides, under the treatment of ad-TGF-β3, a significantly increase was reflected in the expression of TGF-β3 and Smad7, ROM, as well as mechanical strength of flexor tendon, whereas significantly reduction was shown in gliding resistance, the content of inflammatory cytokines, the ratio of p-JNK/JNK, p-c-Jun/c-Jun, as well as the expression of TGF-β1/2, Smad3, Mmp9, and Mmp2 genes, as compared to those from vehicle treatment. Meanwhile, TGF-β3 demonstrated a better pathologic recovery process with no obvious necrosis or fracture of collagen fibers. Besides, TGF-β3 revealed a significant reduction of collagen type-III expression in the flexor tendon healing tissues.ConclusionThese findings suggested that TGF-β3 effectively protected against flexor tendon injury via regulating adhesion formation.

Inhibition of glucose use improves structural recovery of injured Achilles tendon in mice.

Injured tendons do not regain their native structure except at fetal or very young ages. Healing tendons often show mucoid degeneration involving accumulation of sulfated glycosaminoglycans (GAGs), but its etiology and molecular base have not been studied substantially. We hypothesized that quality and quantity of gene expression involving the synthesis of proteoglycans having sulfated GAGs are altered in injured tendons and that a reduction in synthesis of sulfated GAGs improves structural and functional recovery of injured tendons. C57BL6/j mice were subjected to Achilles tendon tenotomy surgery. The injured tendons accumulated sulfate proteoglycans as early as 1-week postsurgery and continued so by 4-week postsurgery. Transcriptome analysis revealed upregulation of a wide range of proteoglycan genes that have sulfated GAGs in the injured tendons 1 and 3 weeks postsurgery. Genes critical for enzymatic reaction of initiation and elongation of chondroitin sulfate GAG chains were also upregulated. After the surgery, mice were treated with the 2-deoxy-d-glucose (2DG) that inhibits conversion of glucose to glucose-6-phosphate, an initial step of glucose metabolism as an energy source and precursors of monosaccharides of GAGs. The 2DG treatment reduced accumulation of sulfated proteoglycans, improved collagen fiber alignment, and reduced the cross-sectional area of the injured tendons. The modulus of the 2DG-treated groups was higher than that in the vehicle group, but not of statistical significance. Our findings suggest that mucoid degeneration in injured tendons may result from the upregulated expression of genes involved the synthesis of sulfate proteoglycans and can be inhibited by reduction of glucose utilization.

Ginsenoside Rg1 enhances the healing of injured tendon in achilles tendinitis through the activation of IGF1R signaling mediated by oestrogen receptor

BackgroundDuring the pathogenesis of tendinopathy, the chronic inflammation caused by the injury and apoptosis leads to the generation of scars. Ginsenoside Rg1 (Rg1) is extracted from ginseng and has anti-inflammatory effects. Rg1 is a unique phytoestrogen that can activate the estrogen response element. This research aimed to explore whether Rg1 can function in the process of tendon repair through the estrogen receptor. MethodsIn this research, the effects of Rg1 were evaluated in tenocytes and in a rat model of Achilles tendinitis (AT). Protein levels were shown by western blotting. qRT-PCR was employed for evaluating mRNA levels. Cell proliferation was evaluated through EdU assay and cell migration was evaluated by transwell assay and scratch test assay. ResultsRg1 up-regulated the expression of matrix-related factors and function of tendon in AT rat model. Rg1 reduced early inflammatory response and apoptosis in the tendon tissue of AT rat model. Rg1 promoted tenocyte migration and proliferation. The effects of Rg1 on tenocytes were inhibited by ICI182780. Rg1 activates the insulin-like growth factor-I receptor (IGF1R) and MAPK signaling pathway. ConclusionRg1 promotes injured tendon healing in AT rat model through IGF1R and MAPK signaling pathway activation.

Macrophage-activating lipoprotein (MALP)-2 impairs the healing of partial tendon injuries in mice

Tendon injuries are accounted for up to 50% of musculoskeletal injuries and often result in poor outcomes. Inflammation is a major hallmark of tendon regeneration. Therefore, we analyzed in this study whether the topical application of the pro-inflammatory mediator macrophage-activating lipoprotein (MALP)-2 improves the healing of partial tendon injuries. C57BL/6 mice underwent a partial tenotomy of the flexor digitorum longus tendon of the left hind limb, which was treated with a solution containing either 0.5 µg MALP-2 or vehicle (control). Repetitive gait analyses were performed prior to the surgical intervention as well as postoperatively on days 1, 3, 7, 14 and 36. The structural stability of the tendons was biomechanically tested on day 7 and 36. In addition, Western blot analyses were performed on isolated tendons that were treated in vitro with MALP-2 or vehicle. In both groups, partial tenotomy resulted in a pathological gait pattern during the initial postoperative phase. On day 7, the gait pattern normalized in vehicle-treated animals, but not in MALP-2-treated mice. Moreover, the tendons of MALP-2-treated mice exhibited a significantly reduced biomechanical stiffness after 7 and 36 days when compared to controls. Western blot analyses revealed a significantly higher expression of heme oxygenase (HO)-1 and lower expression of cyclin D in MALP-2-treated tendons. These findings indicate that MALP-2 delays the healing of injured tendons most likely due to increased intracellular stress and suppressed cell proliferation in this naturally bradytrophic tissue. Hence, the application of MALP-2 cannot be recommended for the treatment of tendon injuries.

Tenascin-C regulates migration of SOX10 tendon stem cells via integrin-α9 for promoting patellar tendon remodeling.

Insufficient attention has been focused on the directional migration of SOX10+ tendon stem cells (STSCs) during tendon remodeling. Here, we investigate whether tenascin-C (TNC) promotes STSC motility and migration. Based on the hypothesis that TNCs induce STSC migration, RNA-sequencing (RNA-seq) was conducted, identifying 2107 differentially expressed genes (DEGs), of which 1272 were up-regulated and 835 down-regulated following treatment with TNC versus the control. The DEGs were principally involved in cell adhesion and cell membrane signal transduction. Highly enriched-related signaling included the PI3K-Akt, focal adhesion, and ECM-receptor interaction pathways. Protein interaction analysis established that TNC was positively correlated with ITGA9 (integrin-α9). Furthermore, TNC activated the phosphorylation levels of FAK and Akt, and knockdown of ITGA9 with siRNA revealed that TNC contributes to STSC migration via the targeting of ITGA9. In addition, in vivo administration of TNC promoted tissue regeneration of injured tendons. In conclusion, TNC regulated the migration of STSCs via ITGA9, thereby promoting the regeneration of tendon injuries.

Return to the original sport at only 3 months after an Achilles tendon rupture by a combination of intra-tissue injection of freeze-dried platelet-derived factor concentrate and excessively early rehabilitation after operative treatment in a male basketball player: A case report.

BackgroundAchilles tendon rupture is one of the most common serious injuries in athletes. Various studies to accelerate the healing process of the Achilles tendon have been performed as it takes a longer time to repair the tissue compared to other tendons. Here, we report a case of an acute Achilles tendon rupture in a male basketball player treated by a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate, which included a platelet-derived growth factor with an early rehabilitation protocol after the operative treatment to facilitate the biological healing of the injured tendon tissue. To the best of our knowledge, this case is the first instance that enabled the athlete to return to original sport activity at only 3-months after the injury.Case reportA 23-year-old male basketball player who belonged to a university basketball team sustained an Achilles tendon rupture during running in a training match. The remaining time period until the final tournament of the university league as a senior player was only 3 months. The patient received a combination of an intra-tissue injection of freeze-dried platelet-derived factor concentrate and early rehabilitation protocol after operative treatment. Surgery was performed 4 days after the injury and the early rehabilitation protocols were applied postoperatively. A freeze-dried platelet-derived factor concentrate was injected into the ruptured site of the Achilles tendon under ultrasound guide at 4 weeks postoperatively. The patient could return to play at the pre-injury level without any symptoms and disfunctions at 3 months after surgery. At two years postoperatively, the patient could play basketball without symptoms or rerupture.ConclusionsWe reported a case of an Achilles tendon rupture which was treated by a combination of intra-tissue injection of freeze-dried platelet-derived factor concentrate and an early rehabilitation protocol after the operative treatment. The patient could return to play basketball at the pre-injury activity level at only 3-months after the injury, suggesting that the role of applying excessively early rehabilitation of mechanical loading could facilitate tendon tissue healing when combined with an intra-tissue injection of freeze-dried platelet-derived factor concentrate.

Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair.

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

Sustained-Release Hydrogel-Based Rhynchophylline Delivery System Improved Injured Tendon Repair

During the injured flexor tendon healing process, tendon tissue is easy to form extremely dense adhesion with the surrounding tissue, which causes the serious influence of hand function recovery. Uncaria is widely used in clinic and its main composition, Rhynchophylline (Rhy), has been reported on its good therapeutic effect, which could effectively inhibit the intra-abdominal adhesion formation. However, the therapeutic effect of Rhy on tendon healing and adhesion formation is still unclear. Due to the short half-life of Rhy, hyaluronic acid (HA) sustained-release system for Rhy delivery was constructed and it could also avoid drug from the undesired loss during the transit. After Rhy delivery system was applied around the injured tendons, adhesion formation, gliding function and healing strength of tendons were evaluated. Our results showed that the gliding excursion and healing strength of repaired tendons were both significantly increased, as well as the adhesion was inhibited. From in vivo experiments, Rhy could be able to increase the expression of Col Ⅰ/Col Ⅲ and helped fibroblasts to ordered organization for tendon tissues. But for adhesion tissues, Rhy promoted the apoptosis and accelerated the degradation of extracellular matrix. In vitro study showed Rhy could help tenocytes stimulated with TGF-β1 to recover to normal cell functions involving cell proliferation and apoptosis level. Through high-throughput sequencing, we found that Rhy was involved in the regulation of Extracellular Matrix (ECM) signaling pathway. We draw a conclusion that Rhy enhanced the tendon healing and prevented adhesion formation through inhibiting the phosphorylation of Smad2. In a word, this sustained release system of Rhy may be a promising strategy for the treatment of injured tendons.

Acmella oleracea extract increases collagen content and organization in partially transected tendons.

Acmella oleracea contains spilanthol as the main active compound, which possesses analgesic and anti-inflammatory effects that can favor tendon reorganization. To analyze the effect of A. oleracea on the content and organization of collagen in injured tendons, the calcaneal tendon of male Lewis rats was partially transected and treated at the site of injury with a topical application of 20% A. oleracea ointment (AO group) or with the ointment base without the plant extract (B group). The animals were euthanized 21 days after partial transection. Higher collagen concentration was observed in the AO group than in the B group, and morphological analysis using polarization microscopy showed higher birefringence in the AO group than in the B group, indicating higher collagen organization. No difference was observed in the number of fibroblasts, blood vessels, proteoglycan distribution, and maximum load between the B and AO groups. In conclusion, topical application of 20% A. oleracea ointment increased the molecular organization and content of collagen, thus indicating a potential application in tendon repair. Studies on the later phases of the tendon healing process are necessary to demonstrate the possible biomechanical changes after the application of A. oleracea ointment.

Evaluation of Hand Tendon Elastic Properties During Rehabilitation Through High-Frequency Ultrasound Shear Elastography.

Tendon injuries lead to tendon stiffness, which impairs skeletal muscle movement. Most studies have focused on patellar or Achilles tendons by using ultrasound elastography. Only a few studies have measured the stiffness of hand tendons because their thickness is only 1-2 mm, rendering clinical ultrasound elastography unsuitable for mapping hand tendon stiffness. In this study, a high-frequency ultrasound shear elastography (HFUSE) system was proposed to map the shear wave velocity (SWV) of hand flexor tendons. A handheld vibration system that was coaxially mounted with an external vibrator on a high-frequency ultrasound (HFUS) array transducer allowed the operators to scan hand tendons freely. To quantify the performance of HFUSE, six parameters were comprehensively measured from homogeneous, two-sided, and three-sided gelatin phantom experiments: bias, precision, lateral resolution, contrast, contrast-to-noise ratio (CNR), and accuracy. HFUSE demonstrated an excellent resolution of [Formula: see text] to distinguish the local stiffness of thin phantom (thickness: 1.2 mm) without compromising bias, precision, contrast, CNR, and accuracy, which has been noted with previous systems. Human experiments involved four patients with hand tendon injuries who underwent ≥2 months of rehabilitation. Using HFUSE, two-dimensional SWV images of flexor tendons could be clearly mapped for healthy and injured tendons, respectively. The findings demonstrate that HFUSE can be a promising tool for evaluating the elastic properties of the injured hand tendon after surgery and during rehabilitation and thus help monitor progress.