Chronic Achilles tendinopathy is characterised by sub-acute inflammation with pro-inflammatory type 1 macrophages (M1), tissue degeneration and consequent partial or total tendon injury. Control of the inflammatory response and M1-to-M2 macrophage polarisation can favour tendon healing both directly and indirectly, by allowing for the regenerative process driven by local mesenchymal stem cells. Ten patients (3 females and 7 males aged between 32 and 71 years old) with partial Achilles tendon injury were treated with injections of autologous peripheral blood mononuclear cells (PB-MNCs). The cell concentrate was obtained from 100-120 cc of each patient's blood with a selective point-of-care filtration system. PB-MNCs remained trapped in the filter and were injected immediately after sampling. Around 60% of the PB-MNC concentrate was injected directly into the injured area, while the remaining 40% was injected in smaller amounts into the surrounding parts of the Achilles tendon affected by tendinosis. All patients were evaluated both clinically with the help of the American Orthopaedic Foot & Ankle Society (AOFAS) scale, and radiologically (MRI examination) at baseline and 2 months after the PB-MNC injection. A clinical reassessment with the AOFAS scale was also performed 6 months after the intervention. The rehabilitation protocol implied full weight-bearing walking immediately after the procedure, light physical activity 3-4 days after the injection, and physiotherapist-assisted stretching exercises and eccentric training. In all patients, functional and radiological signs of tendon healing processes were detected as early as 2 months after a single treatment and the AOFAS scale rose from the initial mean value of 37.5 (baseline) to 85.4 (6 months). Our preliminary results indicate that regenerative therapies with PB-MNCs can prove useful for partial Achilles tendon injuries as a valid alternative to surgical options, especially when other conservative approaches have failed. Advantages of this therapy include rapid execution, no need for an operating theatre, easy reproducibility, quick recovery and good tolerability regardless of the patient's age (the procedure is not to be performed in subjects who are below 18 years old). Further studies on the topic are recommended to confirm these observations

The aim of the study is to determine the histological, biochemical, and biomechanical efficacy of fibrin clot and vitamin C in the healing of Achilles tendon ruptures (ATR) in a rat model.52 adult Wistar Albino rats (300–450 g) were used in the study. 12 groups were divided into four groups as Monitor (Group I), Control (Group II), Fibrin Clot (Group III), Fibrin Clot with vitamin C (Group IV). Four rats were used to obtain fibrin clots. Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) were measured in the blood of tail vein (1 cc) on the 3rd, 7th, 14th, and 21st day. Four rats were sacrificed on the 21st day from each group for histological evaluation. The rest of the rats were sacrificed at 42nd day, half for biomechanical and a half for histological evaluation.

The 42nd-day HSS scores in group III and group IV were significantly lower than those of group I and group II (p =0.036 and 0.019; respectively). The 42nd-day HSS score of group IV was significantly lower than group III (p =0.036). The Maximum force N value of group III and group IV was significantly higher than those of group I and group II (p <0.05). Group IV showed a significantly higher Maximum force N value than group III (p =0.025). The blood FGF and VEGF levels of group III and group IV on the 3rd, 7th, 14th, and 21st days were higher than those of group I and group II (p <0.05).

In the experimentally formed ATR model, fibrin clot and vitamin C produced a stronger tendon structure in terms of biomechanics while providing histological and biochemically better quality tendon healing in the surgical treatment of ATR. We believe that this model can be used to accelerate high-quality tendon healing after ATR.

Aims

Achilles tendon re-rupture (ATRR) poses a significant risk of postoperative complication, even after a successful initial surgical repair. This study aimed to identify risk factors associated with Achilles tendon re-rupture following operative fixation.

The subjective functional outcome and factors affecting patient satisfaction were assessed following tendo Achilles injury which was treated either by conservative (42.4%) or surgical (57.6%) methods.

This is a retrospective study on 35 patients treated for tendo Achilles injury at Airedale General Hospital with a mean follow up time of 2 years (range nine months to four years). A questionnaire ascertained pre and post injury leisure time activity level, occupational change and overall satisfaction with treatment. Case-notes were reviewed for mechanism of injury, time of referral to specialist,previous tendon pathologies,treatment details and complications. Fifty-two patients were contacted and 35 responded. The mean age was 52.7 years (range 33 to 90); 27.3% are involved in office work, 27.3% doing manual work, 15.2% doing job which involves standing most of their time (teacher), 27.2% were leading a retired life and remaining were house wives.

Nobody has changed their occupation. Seventy percent were very satisfied with treatment (analogue score 7–10). The remaining patients complained of pain, stiffness and weakness of ankle and they could not fully get back to their previous leisure time activities. Statistically the operative and conservative groups did not show any difference in the level of satisfaction. The age, sex, occupation and level of sports activities undertaken did not have any significant bearing on satisfaction level. Decreased post injury leisure time activities significantly affected the satisfaction score (p=0.003). Sixty percent of subjects took less than six months to reach there pre-injury activity level. Another significant finding was that the group who presented late for treatment (range 15 days to 1.4 years) was less satisfied (p=0.015). There was some evidence (p=0.034) from regression analysis that physiotherapy intervention increased post injury activity and the satisfaction level. There were 2 reruptures in the conservative group but no other major complications.

To conclude, there were no differences in satisfaction following surgical or conservative management. The reduced post injury leisure time activities, delay in treatment and physiotherapy determined the final outcome.

Background: There is abundant literature on the treatment of Achilles tendon rupture; however data on sports and recreational activities after this injury is scarce.

Patients and Methods: 71 patients were assessed in a prospective cross-sectional study after an average of 3 years after Achilles tendon rupture. 44 patients were treated non-operatively, using a functional algorithm, and 23 patients were treated operatively. Outcome parameters were the AOFAS-Score and the SF-36 Score. The strength of plantar-flexion was measured using the Isomed 2000 system, the structural integrity of the tendon was assessed sonografically.

Results: Patients treated operatively had a higher complication rate than patients treated non-operatively (p=0.05). Re-rupture rate was identically in both groups. No difference was noted between the two groups for the AOFAS score (92 vs. 90). Moreover the SF-36 score did not show any significant difference between the groups. However, if compared to the age-adjusted normative population significant lower scores were achieved. A significant reduction in practicing sports was detected, as well as a reduction of plantar flexion of the affected foot (p=0.04).

Conclusion: Except for complication rate no significant difference could be detected between the groups. Thus operative treatment in the recreational athletes should only be considered, if no adaptation of the ends of the tendon is diagnosed during the initial or repeated ultrasound. Regardless of the therapeutic intervention chosen an Achilles tendon rupture leads to marked changes in sports- and recreational activities.

Electromechanical coupling (piezoelectricity) is present in all living beings and provides basis for sense, thoughts and mechanisms of tissue regeneration. Herein, we ventured to assess the influence of MMC in mesenchymal stem cell culture. In this study, we fabricated piezoelectric regenerative scaffolds to assess the role of electromechamical stimulation on tendon regeneration. Tendon cells were selectively stimulated in vitro by mechanical or electromechanical cues using non-piezoelectric or piezoelectric scaffolds and optimal mechanical loading (4% deformation at 0.5 Hz). This was followed up with an in vivo study to assess tendon regeneration in a rat Achilles tendon injury model. P(VDF-TrFE), scaffolds were observed to mimic the fibrous structure of tendon tissue (figure 1) and were capable of producing electrical charges up to 17 pC/N when mechanically loaded (figure 1. Genes associated with tendon specific markers (Col.I/Col III, Scx and Mkx) and mechanosensitive ion channels such as PIEZO1, TRAAK and TRPV1 were significantly upregulated (figure 2). The upregulated genes were validated with individual real time Q-PCR and bioinformatics revealed a possible regulated function. Those results were further validated in vivo. Protein expression of repaired tendons showed a correlation between increase in expression of tendon related proteins SCX, TNMD, Decorin and expression of ion channels KCNK2, TRAAK and TRPV1. Collectively, these data clearly illustrate that scaffolds made of PVDF-TrFE can produce electrical charges when mechanically loaded. Moreover, gene and protein analyses showed a positive regulation of tendon specific markers through activation mechanosensitive voltage-gated genes. For any figures or tables, please contact authors directly

Introduction. The dichotomy between surgical repair and conservative management of acute Achilles tendon ruptures has been eliminated through appropriate functional management. The orthoses used within functional management however, remains variable. Functional treatment works on the premise that the ankle/hindfoot is positioned in sufficient equinus to allow for early weight-bearing on a ‘shortened’ Achilles tendon. Our aim in this study was to test if 2 common walking orthoses achieved a satisfactory equinus position of the hindfoot. Methods. 10 sequentially treated patients with 11 Achilles tendon injuries were assigned either a fixed angle walking boot with wedges (FAWW) or an adjustable external equinus corrected vacuum brace system (EEB). Weight bearing lateral radiographs were obtained in plaster and the orthosis, which were subsequently analysed using a Carestream PACS system. The Mann-Whitney test was used to compare means. Results. Initial radiographs of all patients in cast immobilization showed a mean tibio-talar angle (TTA) of 55.67° (SD1.21) and a mean 1. st. metatarsal-tibia angle (1MTA) of 73.83° (SD9.45). There were 6 Achilles tendons treated in the FAWW. Their measurements showed a mean TTA of 27.67°(SD7.71) and 1MTA 37.00 (5.22). 5 tendons were treated using an EEB; there was a statistically significant (p< .05) increase in both the TTA 47.6° (SD5.90) and 1MTA 53.67 (SD5.77) compared to the FAWW group. Discussion. Plantar-flexion at the ankle was significantly greater in the EEB comparative to the FAWW, and very similar to the initial equinus cast. The use of wedges produced an equinus appearance through the midfoot, without producing equinus in the hindfoot as the heel pad rests on the top wedge. We express caution in the use of wedges for Achilles treatment as they do not shorten the Achilles tendon and may result in a lengthened tendon and reduced plantar-flexion power in the long-term

Previous studies have shown that Tnmd is important for tendon maturation and has key implications for the residing tendon stem/progenitor cells. The putative signaling in which Tnmd participates is just starting to be better understood (Dex et al. 2016). However, its exact functions during tendon healing process still remain elusive. Therefore, the aims of this study were to perform systematic review of the literature on Tnmd-related research and to investigate the role of Tnmd in early tendon healing by applying a tendon rupture model in Tnmd-deficient mice. First, we searched in the PubMed database for articles containing “tenomodulin” or its alternative names and abbreviations. After exclusion of papers only available in abstract form and foreign language, we grouped the remaining 128 full-text publications into four study types: 1) looking into functions of Tnmd; 2) using Tnmd as a tendon marker; 3) correlating Tnmd mutations to a variety of diseases; and 4) reviews. Following literature analysis, we carried out a pilot Achilles tendon injury model with Tnmd-knockout (KO) mouse strain. Adult Tnmd-KO (n = 8) and wild-type (WT) (n = 8) mice underwent unilateral surgery of Achilles tendon based on Palmes et al. 2002 and were compared at day 8 postoperatively by: 1) H&E staining for overall assessment; 2) immunohistochemical BrdU analysis for cell proliferation; and 3) Safranin O staining for endochondral formation. Our literature screen revealed that Tnmd has been strongly justified as the best tendon and ligament marker in more than 90 different studies. Moreover, in vivo and in vitro investigations have demonstrated its positive role on tendon cell proliferation and tissue functions. Our follow up surgical study showed a very different scar organization in Tnmd-KO with a clearly reduced cell density. BrdU analysis confirmed a lower number of proliferating cells in Tnmd-KO scar area. Interestingly, endochondral formation was not observed in the scar tissues in either of the genotypes at day 8. Taken together, we systematically summarized the current knowledge on Tnmd gene and highlighted several future research perspectives. Lack of studies on the role of Tnmd in tissue healing, motivated our pilot investigation on Achilles tendon rupture, which in turn suggested that loss of Tnmd results in inferior repair process

Background. Despite the suggestion by Virchow in 1856 that thrombosis was the result of venous stasis, endothelial dysfunction and hypercoagulability there are some fundamental questions which remain to be answered. The published studies fail to provide specific details such as cast type and anatomical location of the thrombosis, but instead focus on the incidence of VTE and which chemical thromboprophylaxis is most effective. Previous studies of VTE in trauma patients have involved small numbers of patients and have not look at the risk medium to long term risk. Most importantly they have not looked at the site of the VTE. This makes interpretation of the link between cast and VTE even more complex. Methodology. We analysed 1479 consecutive trauma cast applications and the incidence of symptomatic VTE in the six months following the injury. The diagonosis, cast type and site of the VTE was recorded. Results. The overall incidence of DVT was 2.5% (2.2% distal and 0.3% proximal), 50% occured inthe first 3 weeks, the rest were between 6–13 weeks. The incidence of PE was 0.7%, there was 1 death due to PE. Achilles tendon injury was a statistically significant risk factor, there were no other conditions with a specific risk. There was no difference between above and below knee cast immobilisation. However all symptomatic DVTs occured in the casted leg. Discussion. This is the first study to look at long term VTE risk and the site of thrombosis, these findings have implications for VTE prophylaxis. It would appear that the risk of developing symptomatic VTE extends beyound the currently advised treatment period. It also suggests that venous stasis and endothelial damage are more important that hypercoagulability in the development of VTE after cast treatment for trauma. We recommend a programme of exercises within the cast to reduce this risk

Summary Statement. Subject specific FE models of human Achilles tendon were developed and optimum material properties were found. Stress concentration occurred at the midsection but dependent on stiffening and thinning of tendon, indicating that they are two major factors for tendon rupture. Introduction. Achilles tendon injuries are common, occurring about 250,000 per year in the US alone, yet the mechanisms of tendinopathy and rupture remain unknown. Most Achilles tendon ruptures occur at 2 to 6 cm above the insertion to the calcaneus bone. Previous angiographic studies have suggested that there is an avascular area in this region. However, it is not understood why that region receives poor blood supply and prone to rupture. The aim of this study is to investigate influence of geometry and material properties on Achilles tendon rupture with mechanical experiment and corresponding subject-specific finite element (FE) analysis. Patients & Methods. Mechanical experiment was performed on 10 fresh human Achilles tendons. High frequency ultrasound images were used to measure cross sectional areas at the midsection of the tendon. Cyclic testing was performed to measure mechanical properties and failure loads. Subject-specific FE models of these tendons were generated with Free Form Deformation (FFD) technique. FE mechanical simulations that mimic the experimental cyclic loading were performed on these subject specific models. Tendon material properties were described as transversely isotropic hyperelastic and the optimum material parameters for the human Achilles tendon were obtained. Linear portion of the cyclic loading data was used as boundary conditions. Measured strains from the experiment were compared with predicted strains from the FE analysis. This process was repeated until optimum parameters were found. The influence of geometry and material properties on the Achilles tendon rupture was then investigated– first with subject-specific geometry with average material properties and then with subject-specific material properties with average geometry. Results. Our results indicate that a significant variation exist in the geometry and material properties in human Achilles tendons. Stress concentrations occurred at the midsection of the tendon, supporting previous studies that reported tendon rupture at the region. In particular the thinning of midsection in geometry is highly correlated with the collagen uncrimpping rate in material properties where thinner midsection leads to faster uncrimpping of collagen fibres. Variations in geometry led to shifts in the location of stress concentration within the midsection while variations in material property led the change in the magnitude of stress concentration. Discussion/Conclusion. Our results indicate that Achilles tendon rupture is highly dependent on subject-specific geometry and material properties. In particular the mid section is the location of stress concentration but depending on the geometrical shape, multiple stress concentrations occur, making the tendon more prone to rupture while the material properties influenced the magnitude of stress concentration. Our results indicate stiffening and thinning of tendon may lead to higher risk for tendon rupture

In January 2000 we introduced identical guidelines for the more rapid rehabilitation of Achilles tendon ruptures, whether treated operatively or non-operatively. A relaxed equinus cast was used to four weeks, then a CAM walker to eight weeks with supervised mobilisation. The aims of this study were to compare the outcomes of the operative and non-operative groups treated with the same rehabilitation program and audit the effectiveness of these guidelines. The audit was retrospective from January 2000 till January 2008. The patients were identified from the Emergency Department admissions database, the hospital clinical coding system, the department’s surgical audit data and the hospital physiotherapy appointment system. The audit system was used to identify patients that had complications of their operative treatment, re-ruptures or readmissions. This study focused on the end points of re-rupture, readmission, complications including wound complications and infection. Five hundred and eighty seven presentations were recorded as Achilles tendon injuries. One hundred and eighty patients were treated operatively and 407 patients were treated conservatively. Seventy five patients (42%) treated operatively and 126 patients (30%) of the non-operative group were rehabilitated in our hospital physiotherapy department. The remaining 386 patients (65.7% of all patients) received physiotherapy elsewhere or did not attend for further treatment. In the operative group there were two re-ruptures (1.1%) both treated in our hospital physiotherapy department. There were 2 wound complications (1.1%), one requiring re-operation. In the non operative group there were 15 re-ruptures (3.7%). Of these three had attended the hospital physiotherapy department (rerupture rate of 2.4%) In the non-operative group treated elsewhere there were 12 re-ruptures from 281 patients (4.2%). Comparable results were found between operative and non-operative treatment when combined with close physiotherapy guidance. Non-operatively treated patients treated in the community may have higher re-rupture rates. The results are comparable to those in the literature suggesting that the guidelines are effective

Local dysregulation of the proteolytic matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is a feature of tendon degeneration and rupture. 1. ,. 2. To assess the role of systemic MMPs and TIMPs in tendon rupture we compared serum MMPs and TIMPs between patients who have previously suffered Achilles tendon rupture and healthy controls. We also followed serum MMPs and TIMPs prospectively in patients with acute tendon rupture. At three years after injury, we measured serum MMP-1, -2, -3, -7, -8, -9 and -13 and TIMP-1 and -2 in eight patients who had suffered Achilles tendon rupture. Serum was also obtained from 12 blood donors with similar age and sex distribution. In another eight patients, MMPs and TIMPs were followed over time, with samples taken at the time of Achilles tendon injury, and after 4, 8 and 24 weeks. MMPs were determined using Fluorokine Multi Analyte Profiling kits while TIMPs were analysed using ELISA (R& D systems). The study was approved by the ethics committee and written informed consent was obtained from all patients. Patients who had previously suffered tendon rupture had increased levels of MMP-2 (median difference (m.d.) 10 %; p = 0.01), MMP-7 (m.d. 15 %; p = 0.02) and TIMP-2 (m.d. 36%; p = 0.02), as compared to controls. In patients with acute tendon rupture, MMP-2 was the only MMP or TIMP to change significantly over time (p = 0.009). MMP-7 appeared to be higher than control values already at the time of rupture. MMP-13 could not be detected in any sample. In conclusion, patients with a history of tendon rupture had elevated serum levels of MMP-2, MMP-7 and TIMP-2. Changes in MMP-7 might be present already at the time of rupture. This suggests that disturbances in proteolytic control might render tendons prone to rupture

Summary. Silver nanoparticles improve the tensile property of the repaired Achilles tendon by modulating the synthesis and deposition of collagen. This makes silver nanoparticles a potential drug for tendon healing process with less undesirable side effect. Introduction. Tendon injury is a common injury that usually takes a long time to fully recover and often lead to problems of joint stiffness and re-rupture due to tissue adhesions and scarring on the repaired tendon respectively. Recently, it has been proven that silver nanoparticles (AgNPs) are capable of regenerating skin tissue with minimal scarring and comparable tensile property to normal skin. Hence, it is hypothesised that AgNPs could also improve the healing in tendon injury as both tissues are predominating with fibroblasts. The objective of this study is to look at the in vitro response of primary tenocytes to AgNPs and to investigate the mechanical and histological outcome in vivo. Methods and Materials. Primary tenocytes were harvested from 4 weeks old Sprague Dawley rat. 1.5×10. 4. cells per cm. 2. were seeded in triplicate for BrdU incorporation assay and Sirius red/ fast green staining to study the proliferation and collagen synthesis respectively. In vivo rat Achilles tendon injury model was used to investigate the effect of AgNPs to tendon regeneration. Briefly, the Achilles tendon was transected at 0.5cm from its insertion. The wound was either treated with 1mM AgNPs every 5 days or left untreated as the control. Skin incision was done without transecting the tendon in the sham group. The tendons were harvested on day 42 post operation. Tensile test and immunohistological staining on 7μm cryosections were performed to assess the mechanical property and biological events in healing respectively. SHG imaging was used to determine the collagen fibre orientation and abundance. Results. In vitro BrdU incorporation and Sirius red fast green assay suggested that AgNPs promoted the proliferation and collagen synthesis of tenocytes between 1 to 20μM and 10 to 20μM respectively. Tensile test on in vivo tissue showed that AgNPs-treated samples had significantly better tensile modulus compared to the untreated ones (p<0.05). SHG imaging suggested a better collagen alignment and density in AgNPs-treated samples. Immunohistochemistry demonstrated that AgNPs suppressed tumor necrosis factor (TNF α) whilst promoted fibromodulin (Fmod) and proliferating cell nucleus antigen (PCNA) expression. Discussion. Collagen is the major component that contributes to the tensile strength of a tendon. Its thickness, abundance and alignment directly affect the strength. In this study, it is found that AgNPs stimulate cell proliferation both in vitro and in vivo which is believed to be the reason of the increase in collagen synthesis. Fmod is an important proteoglycan responsible for collagen fibrillogenesis and TNF α is related to ECM degradation which directly affects collagen integrity. Stimulation of Fmod and alleviation of TNF α therefore promote collagen maturity and integrity which attributes to the improvement in the tensile property of the regenerated tissue. Furthermore, inflammation is known to relate to fibrosis and scarring in healing of many types of tissue. It is therefore postulated that the anti-inflammatory effect of AgNPs is one of the major reasons for this phenomenal healing of tendon. To conclude, this study demonstrates a positive effect of AgNPs to the early events of tendon healing which is important for accelerating the whole healing process and shortening of rehabilitation time