Dexamethasone treatment influences tendon healing through altered resolution and a direct effect on tendon cells.

Inflammation, corticosteroids, and loading all affect tendon healing, with an interaction between them. However, underlying mechanisms behind the effect of corticosteroids and the interaction with loading remain unclear. The aim of this study was to investigate the role of dexamethasone during tendon healing, including specific effects on tendon cells. Rats (n = 36) were randomized to heavy loading or mild loading, the Achilles tendon was transected, and animals were treated with dexamethasone or saline. Gene and protein analyses of the healing tendon were performed for extracellular matrix-, inflammation-, and tendon cell markers. We further tested specific effects of dexamethasone on tendon cells in vitro. Dexamethasone increased mRNA levels of S100A4 and decreased levels of ACTA2/α-SMA, irrespective of load level. Heavy loading + dexamethasone reduced mRNA levels of FN1 and TenC (p < 0.05), while resolution-related genes were unaltered (p > 0.05). In contrast, mild loading + dexamethasone increased mRNA levels of resolution-related genes ANXA1, MRC1, PDPN, and PTGES (p < 0.03). Altered protein levels were confirmed in tendons with mild loading. Dexamethasone treatment in vitro prevented tendon construct formation, increased mRNA levels of S100A4 and decreased levels of SCX and collagens. Dexamethasone during tendon healing appears to act through immunomodulation by promoting resolution, but also through an effect on tendon cells.

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).

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.

Regional variations in incidence and treatment trends of Achilles tendon ruptures in Finland: a nationwide study.

BACKGROUND AND PURPOSE: The aim of our study was to assess the regional variations in Achilles tendon rupture incidence and treatment methods in Finland during the period 1997-2019. METHODS: The Finnish National Hospital Discharge Register (NHDR) and the Finnish Register of Primary Health Care Visits (PHCR) were searched to identify all adult patients diagnosed with Achilles tendon rupture during our study period. The population-based annual incidence and incidences of surgically and non-surgically treated Achilles tendon ruptures were calculated for each hospital district. RESULTS: Achilles tendon rupture incidence increased from 17.3 per 105 person-years in 1997 to 32.3 per 105 in 2019. The mean incidence of Achilles tendon ruptures ranged from 26.4 per 105 (North Savo) to 37.2 per 105 (Central Ostrobothnia). The incidence of Achilles tendon ruptures increased in all areas. The proportion of non-surgical treatment of Achilles tendon ruptures ranged in 1997 from 7% (Vaasa) to 67% (Åland) and in 2019 from 73% (Southwest Finland) to 100% (East Savo, Kainuu, Länsi-Pohja, Åland). During the study period, a shift towards non-surgical treatment was evident in all hospital districts. CONCLUSION: Regional variations in Achilles tendon rupture incidence exist in Finland; however, the incidence increased in all areas during the follow-up period. More Achilles tendon rupture patients are currently being treated non-surgically throughout the country.

Investigation of the effects of treatment with enoxaparin sodium and hyperbaric oxygen therapy on the recovery of rats with achilles tendon rupture.

PURPOSE: In this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture. METHODS: Thirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically. RESULTS: The groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores. CONCLUSION: Our study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.

Reduced Intratendinous Sliding in Achilles Tendinopathy During Active Plantarflexion Regardless of Horizontal Foot Position.

PURPOSE: The Achilles tendon consists of three subtendons with the ability to slide relative to each other. As optimal intratendinous sliding is thought to reduce the overall stress in the tendon, alterations in sliding behavior could potentially play a role in the development of Achilles tendinopathy. The aims of this study were to investigate the difference in intratendinous sliding within the Achilles tendon during isometric contractions between asymptomatic controls and patients with Achilles tendinopathy and the effect of changing the horizontal foot position on intratendinous sliding in both groups. METHODS: Twenty-nine participants (13 Achilles tendinopathy and 16 controls) performed isometric plantarflexion contractions at 60% of their maximal voluntary contraction (MVC), in toes-neutral, and at 30% MVC in toes-neutral, toes-in, and toes-out positions during which ultrasound images were recorded. Intratendinous sliding was estimated as the superficial-to-middle and middle-to-deep relative displacement. RESULTS: Patients with Achilles tendinopathy present lower intratendinous sliding than asymptomatic controls. Regarding the horizontal foot position in both groups, the toes-out foot position resulted in increased sliding compared with both toes-neutral and toes-out foot position. CONCLUSION: We provided evidence that patients with Achilles tendinopathy show lower intratendinous sliding than asymptomatic controls. Since intratendinous sliding is a physiological feature of the Achilles tendon, the external foot position holds promise to increase sliding in patients with Achilles tendinopathy and promote healthy tendon behavior. Future research should investigate if implementing this external foot position in rehabilitation programs stimulates sliding within the Achilles tendon and improves clinical outcome.

Tendon extracellular-matrix-derived tissue engineering micro-tissue for Achilles tendon injury regeneration in rats.

BACKGROUND: Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering. METHODS: A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing. RESULTS: The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups. CONCLUSION: Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.

Staying in the Game: Interventions for Managing Achilles Tendinopathy in the In-Season Athlete.

ABSTRACT: Achilles tendinopathy is a common overuse injury that is traditionally managed with activity modification and a progressive eccentric strengthening program. This narrative review describes the available evidence for adjunctive procedural interventions in the management of midportion and insertional AT, specifically in the athletic population. Safety and efficacy data from available literature on extracorporeal shockwave therapy, platelet-rich plasma, high-volume injectate with or without tendon scraping, and percutaneous needle tenotomy are used to propose an algorithm for treatment of Achilles tendinopathy for the in-season athlete.

Incidence, demographics, characteristics and management of acute Achilles tendon rupture: An epidemiological study.

BACKGROUND: Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients' quality of life. The incidence, characteristics and management of ATR in the United Kingdom (UK) is poorly understood. This investigation aims to understand the incidence of ATR in the UK. METHODS: Prospective data collection of ATR incidence from a United Kingdom Emergency department. Retrospective review of management protocols and immobilisation duration from electronic medical records. RESULTS: ATR incidence is 8 per 100,000 people per annum. Participants were predominately male (79.2%) and primarily reported a sporting mechanism of injury (65.2%). Mean immobilisation duration was 63.1 days. 97.1% were non-surgically managed post ATR. 46.2% of participants had experienced a previous ATR or Achilles tendinopathy prior to their current ATR. CONCLUSION: The incidence of ATR found was 8. cases per 100,000 people per annum. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Almost one quarter (23.3%) of individuals report Achilles pain prior to ATR.

Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases.

OBJECTIVE: Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. METHODS: This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. RESULTS: None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). CONCLUSION: The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

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.

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair.

OBJECTIVES: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15th (early period) or 30th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15th and 30th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. RESULTS: Histopathologically, there were no significant differences among the groups on the 15th day. However, on the 30th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). CONCLUSION: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

Achilles Tendon Rupture.

There are many high-level studies comparing nonoperative treatment, open repair, and minimally invasive repair for Achilles tendon ruptures. This article summarizes the most up-to-date literature comparing these treatment options. The authors' preferred protocol for nonoperative treatment is discussed. Preferred techniques for open repair and chronic Achilles repair are discussed with reference to the literature.

Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

In vivo study on the repair of rat Achilles tendon injury treated with non-thermal atmospheric-pressure helium microplasma jet.

Non-thermal atmospheric-pressure plasma (NTAPP) has been widely studied for clinical applications, e.g., disinfection, wound healing, cancer therapy, hemostasis, and bone regeneration. It is being revealed that the physical and chemical actions of plasma have enabled these clinical applications. Based on our previous report regarding plasma-stimulated bone regeneration, this study focused on Achilles tendon repair by NTAPP. This is the first study to reveal that exposure to NTAPP can accelerate Achilles tendon repair using a well-established Achilles tendon injury rat model. Histological evaluation using the Stoll's and histological scores showed a significant improvement at 2 and 4 weeks, with type I collagen content being substantial at the early time point of 2 weeks post-surgery. Notably, the replacement of type III collagen with type I collagen occurred more frequently in the plasma-treated groups at the early stage of repair. Tensile strength test results showed that the maximum breaking strength in the plasma-treated group at two weeks was significantly higher than that in the untreated group. Overall, our results indicate that a single event of NTAPP treatment during the surgery can contribute to an early recovery of an injured tendon.

The learning curve for minimally invasive Achilles repair using the "lumbar puncture needle and oval forceps" technique.

INTRODUCTION: An acute Achilles tendon rupture represents a common tendon injury, and its operative methods have been developed over the years. This study aimed to quantify the learning curve for the minimally invasive acute Achilles tendon rupture repair. METHODS: From May 2020 to June 2022, sixty-seven patient cases who received minimally invasive tendon repair were reviewed. Baseline data and operative details were collected. The cumulative summation (CUSUM) control chart was used for the learning curve analyses. Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, and visual analog scale (VAS) at 3/6/9/12 months were calculated to assess the clinical outcomes. RESULTS: Thirty-six cases underwent at least a year of follow up and were enrolled in this study. The gender ratio and average age were 80.5% and 32.5 years. The linear equation fitted well (R2 = 0.95), and CUSUM for operative time peaked in the 12th case, which was divided into the learning phase (n = 12) and master phase (n = 24). No significant difference was detected between the two groups in clinical variables, except for the operative time (71.1 ± 13.2 min vs 45.8 ± 7.2 min, p = 0.004). Moreover, we detected one case with a suture reaction and treated it properly. CONCLUSION: Minimally invasive Achilles repair provides an opportunity for early rehabilitation. Notably, the learning curve showed that the "lumbar puncture needle and oval forceps" technique was accessible to surgeons.

Salvage Reconstruction of a 12-cm Tendon Defect Following Chronic Achilles Rerupture-15-Year Follow-Up: A Case Report.

CASE: A 39-year-old man with a chronic Achilles rupture status post (1) failed primary repair and (2) secondary xenograft repair with graft rejection, resulting in a 12-cm Achilles tendon defect, which was reconstructed utilizing an Achilles bone block allograft and flexor hallucis longus (FHL) tendon transfer. At 15-year follow-up, the patient reported good functionality and satisfaction with the repair, with positive patient-reported outcome measures. Physical examination revealed excellent strength and range of motion. Magnetic resonance imaging confirmed the integrity and incorporation of the Achilles/FHL graft composite. CONCLUSION: This case study provides valuable insight into successful long-term management of complex chronic Achilles ruptures with large defects.

[Short-term outcomes of all-inside endoscopic running locked stitch technique for acute achilles tendon ruptures].

Objective: To evaluate the short-term outcomes of all-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures. Methods: This is a retrospective case series study. Forty-eight cases with acute Achilles tendon rupture were treated with the all-inside endoscopic running locked stitch technique from April 2020 to March 2022 at Department of Orthopaedics, General Hospital of Central Theater Command. There were 44 males and 4 females, aged (34.8±7.4) years (range: 24 to 50 years). Body mass index was (21.2±2.4)kg/m2 (range: 18 to 26 kg/m2); There were 29 cases (60.4%) on the left side and 19 cases (39.6%) on the right side. Under endoscopic control, the proximal tendon stumps were stitched with the running locked method using a semi-automatic flexible suture passer. The threads of the high-strength suture were grasped through the paratenon sub-space and then fixed into calcaneal insertion with a knotless anchor. MRI of Achilles tendon was performed to observe the regeneration of Achilles tendon during follow-up. Surgical time and complications were assessed. Achilles tendon total rupture score (ATRS), Achilles tendon resting angle, and heel rise height were utilized to evaluate final clinical outcomes. The differences of bilateral limbs were compared using the paired sample t test. Results: The follow-up time was (24.1±3.5)months (range:18 to 32 months). Appropriate tendon regeneration was observed on MRI at 12 months after operation. The median ATRS score (M(IQR)) was 95.0 (4.7) points. Furthermore, there was no significant difference between the injured and contralateral side in the Achilles tendon resting angle ((17.1±2.4)° vs. (17.4±2.6)°, t=1.92,P=0.062) and heel rise height ((14.2±1.7)cm vs. (14.4±1.5)cm, t=1.71,P=0.094). No nerve injury, infection, deep vein thrombosis and re-rupture was encountered. Sports activity resumed six months postoperative in 46 patients. One patient had a slight anchor cut-out, due to an addition injury, which was removed after 5 months. Conclusions: All-inside endoscopic running locked stitch technique for acute Achilles tendon ruptures shows promising results. It provides stable connection of the tendon stumps with a low risk of complications.