Muscle and tendon have an adaptive, symbiotic biomechanical relationship that is drastically altered following acute tendon injury. Such injuries, like Achilles tendon rupture (ATR), do not only lead to impairments in the resultant tendinous tissue, but also to irrecoverable atrophy in the connected muscle in series. As a result, a new relationship between muscle and tendon is established after ATR, leading to lasting functional deficits in the lower limb. It remains unclear how these develop, particularly since this imbalance may be influenced by the dependent relationship of the two tissues to each other. A further confounding factor is that tendon and muscle tissues adapt on different time scales in response to mechanical loading, such as those introduced during rehabilitation. Thus, it is warranted to perform assessments not only of the overall muscle-tendon unit, but also its constituent tissues. This presentation will discuss findings from both short-term and long-term follow-ups of ATR patients, with a focus on the recovery of gait and changes in the muscle-tendon unit tissues following ATR repair. Both the influence of the rehabilitation process and suggestions for future research directions will be additionally presented

Objectives

The evidence base to inform the management of Achilles tendon rupture is sparse. The objectives of this research were to establish what current practice is in the United Kingdom and explore clinicians’ views on proposed further research in this area. This study was registered with the ISRCTN (ISRCTN68273773) as part of a larger programme of research.

Growth factors are reported to play an important role in healing after acute Achilles tendon rupture (ATR). However, the association between growth factors and patient outcome has not been investigated previously. The aim of this retrospective study is to identify growth factors and related proteins which can be used as predictors of healing after ATR, ethical approval was obtained from the Regional Ethical Review Committees in Sweden and followed the guidelines of the Declaration of Helsinki. The study included 28 surgically treated patients (mean age 39.11 ± 8.38 yrs) with acute ATR. Healing was assessed by microdialysate two weeks after the surgery and performed on both injured and contralateral un-injured leg. The microdialysates were analyzed by proteomics based on mass spectrometry (MS) to detect growth factor expressions in ATR patients. One year after the surgery, healing outcomes were evaluated by patient-reported Achilles tendon Total Rupture Score (ATRS), Foot and Ankle Outcome Score (FAOS), and functional outcomes by heel-rise test.

A total of 1549 proteins were detected in the microdialysates of which 20 growth factor/ related proteins were identified. 7 of these were significantly up-regulated (IGFBP2, Fold change (FC) = 4.07, P = 0.0036; IGFBP4, FC = 3.06, P = 0.009; CTGF, FC = 15.83, P = 0.003; HDGF, FC = 4.58, P = 0.003; GRB2, FC = 14.8, P = 0.0004; LTBP1, FC = 12.08, P = 0.0008; TGFBI, FC = 5.54, P = 0.001) and 1 down-regulated (IGFBP6) in the injured compared to the contralateral healthy side. Linear regression analysis revealed that TGFB1 was positively associated with improved ATRS (r = 0.585, P = 0.04) as well to ATRS subscales: less limitation in running (r = 0.72, P = 0.004), less jumping limitation (r = 0.764, P = 0.001) and less limitation caused by decreased tendon strength (r = 0.665, P = 0.012). Interestingly, all 7 up-regulated proteins were positively associated with less jumping limitations (IGFBP2, r = 0.667, P = 0.015; IGFBP4, r = 0.675, P = 0.013; CTGF, r = 0.668, P = 0.015; HDGF, r = 0.672, P = 0.014; GRB2, r = 0.665, P = 0.016; LTBP1, r = 0.663, P = 0,016). No associations were observed among any of the growth factor and FAOS or patient's functional outcomes.

We conclude that growth factors and related proteins play a crucial role in ATR healing. More specifically, TGFB1 may be used as prognostic biomarker of the patient-reported outcome 1-year post-surgery. These results may be used to develop more specific treatments to improve ATR healing.

Introduction. The Achilles tendon is the thickest and strongest tendon in the human body. Even though the tendon is so strong, it is one of the most frequently injured tendons. Treatment of patients after rupture is planned conservatively and surgically. Conservative treatment is generally applied to elderly patients with sedentary lives. If the treatment is surgical, it can be planned as open surgery or percutaneous surgery. In our study with rabbits, we wrapped a membrane made of plga (polylactic-co-glycolic acid) nanotubes impregnated with type 1 collagen around the tendon in rabbits that underwent open Achilles tendon repair surgery. After surgery, biomechanical and histological tests were performed on the tendons. Method. In the study consisting of 24 rabbits, 2 groups were created by random distribution. In the study group, after the Achilles tendon rupture was created, a type 1 collagen-impregnated plga-based membrane was placed around the tendon after the repair of 1 modified Kesslerr suture. In the control group, after the Achilles tendon rupture was created, 1 modified Kessler suture and Tendon repair was performed with the application of 3 primary sutures. At the end of the 6th week of the study, the rabbits in 2 groups were randomly distributed and histological examination was performed. Additionally, biomechanical testing was performed. Bonar and Movın scoring were used in histological examinations. Result. As a result of biomechanical tests, it was seen that the resistance of the tendon against rupture was higher in the study group than in the control group. In addition, it was observed that the tendon rupture time was longer in the study group than in the control group. Histological examinations gave supportive results from biomechanical tests. Conclusion. We think that the use of collagen-impregnated plga-based nanotubes in the surgical treatment of Achilles tendon ruptures has a positive healing effect. Although we think that the return to normal life after surgery may be faster, we believe that more clinical studies are needed

Abstract. Objectives. Achilles tendon ruptures are common in the UK, with data demonstrating a significant rise in incidence over the past years. Chronic Achilles ruptures have been less well defined in literature, and repair techniques vary significantly. A surge in publications reporting various management options for chronic Achilles ruptures has necessitated a review that systematically maps and summarises current evidence regarding treatments and identifies areas for future research. This scoping review aims to improve knowledge of various treatment strategies and their associated outcomes, thereby aiding clinicians in optimising treatment protocols. Methods. The Arksey and O'Malley, Levac and Peters frameworks were used. A computer-based search in PubMed, Embase, Emcare, Cinahl, ISI Web of Science and Scopus was performed for articles reporting the treatment of chronic Achilles ruptures. Two reviewers independently performed title/abstract and full text screening according to a pre-defined selection criteria. Results. A total of 747 articles were identified, of which 73 were finally included. Various management strategies were described with flexor hallucis longus tendon transfer being the most common. The American Orthopaedic Foot and Ankle Society (AOFAS) score was the most commonly reported outcome, but 16 other measures were described within the literatures. All studies comparing pre- and post-operative outcomes reported a significant improvement. 50 studies reported complications, with an overall pooled complication rate of 168/1065 (15.8%). Conclusions. Beneficial results were reported following various techniques, but comparison between these was challenging due to the low-level study designs used and confounding factors including treatment delay and tendon gap size. Further research exploring the efficacy of different techniques is required to facilitate the development of evidenced-based treatment protocols. Such a work would allow for clinicians to better understand the suitability of specific techniques, thereby selecting the optimal management strategy for each individual patient

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

Introduction. The healing of Achilles tendon rupture is slow and jogging is usually allowed already 6 months after injury. However, the metabolic status of the healing tendon is largely unknown at the time-points when increased loading is allowed. The purpose of this study was to investigate tendon metabolic response and blood flow at 3, 6 and 12 months after Achilles tendon rupture by positron emission tomography (PET) and ultrasound-Power Doppler (UPD). Materials and Methods. 23 patients that had surgical repair of a total Achilles tendon rupture (3 (n=7), 6 (n=7) or 12 (n=9) months earlier) participated in the study. The triceps surae complex was loaded during 20 min of slow treadmill walking. A radioactive tracer (FDG) was administered during this walking and glucose uptake was measured bilaterally by the use of PET. Blood flow was recorded by UPD and patient reported outcome scored by Achilles tendon rupture score (ATRS) and VISA-A. Non-parametric statistics were used for statistical analysis. Results. Metabolic activity was higher in the healing tendon compared to intact tendon at all time-points, however the activity decreased over time (510%, 260% and 62% higher on the healing side compared to the intact side at 3, 6 and 12 months respectively, p<0.001). The metabolic activity was higher in the core than the periphery of the healing tendon, at 3 and 6 months (p<0.02), but lower at 12 months (p=0.06). Interestingly, metabolic activity was negatively related to ATRS, 6 months after rupture (r=−0.89, p<0.01). UPD was also 100-fold and 61-fold higher respectively in the healing than the intact healthy tendon at 3 months (p<0.05) and 6 months (p=0.06), but not at 12 months. Discussion. These results demonstrate that the healing process measured by metabolic and blood flow activity still remains high 6 months after rupture when increased loading is allowed. In fact, PET determined metabolic activity remained elevated up to a year after injury when measures of hyper-vascularization were normalized. Although speculative, the strong negative correlation between tendon metabolism and patient reported outcome indicates that a high metabolic activity 6 months after the injury may be related to poor healing outcome

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

Achilles tendon rupture may lead to significant functional deficits, which mechanisms are poorly understood. The primary aim was to investigate if the Achilles tendon (AT) was longer, muscles weaker or gait changed on the injured leg 4–5 years after the injury. Secondary aim was to compare functional outcomes with patient reported Achilles Tendon Total Rupture Score (ATRS). We invited all participants from an RCT of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB), and 12 moths of follow up. Of the original 56, 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol (Barfod K.W. et al.). Heel raise work was measured on a 10 degree inclining platform. The exercise lasted until the patient could not maintain frequency or height of lift. Number and height of lift was measured using reflective markers in a Vicon system, and total work calculated. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany). Statistics: T-test for limb to limb comparisons and linear regression for ATRS correlations was applied. Including RR in the sample did not impact the results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1,8 (1,2–2,3) cm longer on the injured limb, which produced 40% less work. A smaller calf circumference (p < 0.001), larger dorsiflextion (p = 0.001), and Achilles tendon resting angle (p < 0.001) was found for the injured limb. Difference in mean medial forefoot peak pressure was approaching significance (healthy 484 (SD 165) KPa, injured: 439 (SD 160), p = 0.08). Similarly the difference in pressure / time integral of the medial forefoot was approaching significance (Healthy: 129 (SD 35)KPa, injured: 115 (SD 44)KPa, p = 0.08). Duration of contact time of the heel was extended and heel lift off was delayed in the injured limb (p = 0.02 for both). ATRS could not be linked to Achilles tendon length or total work using linear regression. Conservatively treated Achilles tendon ruptures were approximately 1,8 cm longer. The limb was persistently weaker. A subtle change in heel contact duration and time of heel rise could be detected on the injured limb. ATRS does not appear to correlate directly with AT length or loss of total work

Tendon pathologies represent an unresolved clinical challenge where the patients suffer from pain and impaired mobility. One of the most frequently ruptured tendons is the Achilles tendon and primarily seen in recreational and professional athletes. A study from Sweden reported a significant increase in the incidence of Achilles tendon ruptures of 17% in men and 22% in women due to the demographic changes and the higher sportive activity of older adults (Huttunen TT Am J Sports Med 2014). The re-rupture rate is between 2–10%, and the patients suffer from an impairment over a long time accompanied with incapability to work. The healing process results in the formation of a mechanically insufficient scar tissue. A detailed knowledge on the cellular and molecular processes underlying human Achilles tendon healing is necessary to develop new treatment strategies and judge therapeutic success. The analysis of human Achilles tendon samples at different time points post rupture and the comparison to intact and degenerated tendon tissue provides important information on the healing process

Purpose. Functional ultrasound Elastography (FUSE) of Tendo Achilles is an ultrasound technique utilising controlled, measurable movement of the foot to non-invasively evaluate TA elastic and load-deformation properties. The study purpose is to assess Achilles tendons, paratenon and bursa mechanical properties in healthy volunteers and establish an outcome tool for TA treatment. Methods. Forty asymptomatic Achilles tendons of 20 healthy volunteers were recruited (10 men and 10 women, age range 18-55). One patient with Acute Achilles rupture scanned to evaluate the tendon gap. Each volunteer answered the Foot and Ankle Outcome Score (FAOS) and Victorian Institute Sport Assessment score (VISA-A) questionnaires. The Achilles Tendons were divided into three thirds (total 120 Proximal, middle and distal thirds). Three longitudinal images of each third were obtained using portable US scan device (Z.one, Zonare Medical System Inc., USA, 8.5 MHz). Images processing was achieved using a MatLAb software (developed by the research team) in parallel Oxford university computers. Each 1/3rd Achilles tendon under went the following scans: . Free hand US scan. Free hand Compression decompression Elastography scan. Dorsal Flexion elastography. Planter flexion elastography. Zonare real-time Elastography. Elastography scan with the Oxford isometric dynamic foot and Ankle mover (OIDFA). B mode and elasticity images were derived from the raw ultrasound radio frequency data. The anatomical structures mechanical properties were evaluated by a quantitative score of different colours representing stiff tissue (blue) to more soft tissue (green, yellow, red). Results. The Achilles tendons showed mainly a hard structured pattern (82.5%) (99/120 tendon thirds) on sonoelastography; however, mild softening was found in 17.5% (21/120) of the tendons. Therefore, suggesting subclinical changes. The minimal lateral movement of the tendon produced by applying the FOAIDM resulted in well defined elasticity images with tendon in blue colour (stiff) and surrounding soft tissues. The average strain along the tendon was 2% (range 0-6%). The overall correlation (κ) between real-time sonoelastography and ultrasound findings was < 0.3. However, the correlation (κ) between FUSE UEI and US findings was 1.0. Patients with Achilles tendon rupture lateral strain and axial elastography images using FUSE methods revealed a larger gap with spreading of the haematoma along the paratenon. Conclusion. Our findings show that FUSE seems to be a sensitive method for assessment of TA mechanical properties. The B mode and elasticity images must be viewed simultaneously. FUSE method can easily identify the regeneration of ruptured TA. Elasticity and stiffness measurement may offer an invaluable tool to guide TA rupture and tendenopathy treatment and rehabilitation protocols

Background. We prospectively studied achilles tendon acute rupture cases operated over 2 years and reviewed the causes, treatment options, outcome and complications. Our Aim of the study was to look at the different suture materials used and to observe for their complications. Method. Fifty-three (53) consecutive patients who came to our hospital with acute Achilles rupture were included. We prospectively collected their data, including medical history, causes, mode of treatment and complications. We followed them up to 6 months to measure their outcome using Boyden score and observe any complications. Results. We randomised the fifty-three (53) patients into two groups according to admitting consultant. Out of fifty three 53 Achilles tendon ruptures nineteen 19 were repaired using Polyester (Ethibond) and thirty four 34 were repaired using Polydiaxonone (PDS). There were 6 surgical infections of the operative site and one DVT. Conclusion. In majority of patients the functional outcome results were good to excellent according to Boyden score. We observed that all of them who got infection were repaired using non-absorbable polyester (ethibond). We also observed that DVT prophylaxis should be regularly given in the patients

Achilles tendon (AT) rupture may lead to complaints of heel pain. In forefoot ulcer patients AT lengthening is used to transfer pressure from forefoot to the heel. The primary aim was to investigate if AT was longer or associated with changes in pedobaric measurements, in particular heel pressure, on the injured leg 4–5 years after the injury. Methods. We invited all participants from an RCT (n=56) of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB). 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany), with 5 trials for each foot. Statistics. T-test for limb to limb comparisons and linear regression for correlations was applied. Results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1.8 (1.2–2.3) cm longer on the injured limb (p<0.001). When comparing the ratio of the medial (1–2 ray) to lateral (3–5 ray) forefoot mean peak pressure, we found no difference between the injured and healthy limb (p=0.26). Mean heel peak pressure was not different from the injured to the healthy leg (difference was 3,9 (−1,7 – 9,45) p=0,17). Heel lift-off was delayed in the injured limb by 2% (0.4%–4.4%) of the total roll over process (ROP) (p= 0.02). Achilles tendon length could not be linked to either heels lift-off or mean peak pressure of the heel using linear regression (p 0.27 to 0.78). Conclusion. Conservatively treated Achilles tendon ruptures were approximately 1.8 cm longer. A subtle change in the time of heel rise could be detected on the injured limb, but contrary to our expectations AT length did not correlate to time of heel lift or mean heel peak pressure. This is in contrast to the common practice in diabetics, where the Achilles tendon is elongated to relieve pressure from the forefoot – a mechanism we cannot observe from elongation of the tendon after acute rupture, treated conservatively - though this study is underpowered

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

Introduction. The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering tendon tissue degeneration. By analysing the expression of the entirety of degrading enzymes (degradome) in pathological and non-pathological, strained and non-strained tendon tissue, the aim of this study was to identify common or opposite patterns in gene regulation. This approach may generate new targets for future studies. Materials and Methods. RNA was extracted from different tendon tissues: normal (n=7), tendinopathic (n=4) and ruptured (n=4) Achilles tendon; normal (n=4) and tendinopathic (n=4) posterior tibialis tendon; normal hamstrings tendon with or without subjection to static strain (n=4). The RNA was reverse transcribed, then pooled per group The expression of 538 protease genes was analysed using Taqman low-density array quantitative RT-PCR. To be considered relevant, changes had to be at least 4fold and measurable at a level below 36 Cts. Results. In general, there was little common regulation when exercised was compared with pathological tissue. The expression of PAMR1 and TNFαIP3 was upregulated with exercise (169-fold and 78-fold), Achilles tendinopathy (9724-fold and 7-fold) and Achilles tendon rupture (1809-fold and 10-fold), while DDI1, PSMB11 and PSH2 which were down-regulated with exercise were upregulated with Achilles pathology. Discussion. The newly found targets may deliver insights into the initiation and progression of tendon pathologies: PAMR1, a regeneration associated muscle protease which has been shown to be downregulated in Duchenne muscular dystrophy and upregulated in regenerating muscle fibers, might also be involved in tendon regeneration; TNFαIP3, which negatively regulates the NF-κB/pro-inflammatory pathway, could have anti-inflammatory function in tendon regeneration. PSMB11 and PSH2 are for the first time shown to be expressed in tendon and regulated in tendon pathology. Using this approach we were able to generate new targets and to add information on function, regulation and expression sites of recently identified proteins

Purpose. Platelet Rich Plasma (PRP) has been shown to have positive effect in tendon regeneration in in-vitro and limited in-vivo animal studies. We aim to study PRP use in acute Achilles tendon rupture (ATR) regeneration in a purposely designed clinical trial. Methods. This is a prospective double-arm patient-blinded randomized controlled trial. ATR patients were randomized into PRP treatment or control groups. Non-operatively treated patients received PRP or control injection in clinic. In operatively treated patients, PRP gel was applied in the ruptured gap during percutaneous repair. Standard rehabilitation protocol was used and patients were followed up for 24 weeks. ATR, VISA-A and FAOS scores were used as subjective outcome measures. Functional ultrasound Elastography (FUSE) was performed at each follow-up to assess the mechanical properties of tendons. PRP analysis and tendon needle-biopsy were performed to study the histological differences during healing in both groups. Results. 20 patients were recruited with mean age 37.5±8.8 (8males and 7 females). Rupture location was 4.8±2.1 cm from insertion. PRP platelet count 1044±320 × 1000/μL with average platelet CD62p activation 68.42±4.5%. Mixed linear regression analysis revealed PRP treated tendon achieved better ATR and VISA-A outcome scores (p<0.05). FAOS score analysis showed that PRP group had better pain, ADL and symptoms scores with significant difference apparent from week 3 onwards. Strain mapping using FUSE scan in 4 patients showed bigger harder tendons in PRP group. Analysis of the remaining patients is on the way. To achieve the desired statistical power in pragmatic settings, recruitment will continue in a multi-centre trial. Conclusion. Our preliminary findings show that PRP application in Achilles tendon rupture may lead to faster regeneration and return to function as supported by a combination of objective and subjective outcome measures