Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors. Cite this article: Bone Joint Res 2022;11(8):561–574

Objectives. Inflammation of the retrocalcaneal bursa (RB) is a common clinical problem, particularly in professional athletes. RB inflammation is often treated with corticosteroid injections however a number of reports suggest an increased risk of Achilles tendon (AT) rupture. The aim of this cadaveric study was to describe the anatomical connections of the RB and to investigate whether it is possible for fluid to move from the RB into AT tissue. Methods. A total of 20 fresh-frozen AT specimens were used. In ten specimens, ink was injected into the RB. The remaining ten specimens were split into two groups to be injected with radiological contrast medium into the RB either with or without ultrasonography guidance (USG). Results. In specimens injected with ink, diffusion outside the RB was observed with staining of the anterior portion of the AT. In eight contrast-injected specimens (five USG, three non-USG), a similar localised diffusion pattern was observed, with the contrast identified superiorly and anteriorly. In two contrast-injected specimens (non-USG), the diffusion pattern was more extensive. Conclusion. This study confirmed the existence of connections between the RB and the AT, especially rich in the anteroinferior portion of the tendon, which should be considered a weak zone for substances injected into the RB. We hypothesise that this part of the AT might be most vulnerable to rupture after corticosteroid injections. Cite this article: P. A. Pękala, B. M. Henry, J. R. Pękala, K. Piska, K. A. Tomaszewski. The Achilles tendon and the retrocalcaneal bursa: An anatomical and radiological study. Bone Joint Res 2017;6:446–451. DOI:10.1302/2046-3758.67.BJR-2016-0340.R1

Objectives. The goals of this study were: 1) to determine if high-fat diet (HFD) feeding in female mice would negatively impact biomechanical and histologic consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate whether exercise and branched-chain amino acid (BCAA) supplementation would affect these parameters or attenuate any negative consequences resulting from HFD consumption. Methods. We examined the effects of 16 weeks of 60% HFD feeding, voluntary exercise (free choice wheel running) and BCAA administration in female C57BL/6 mice. The Achilles tendons and quadriceps muscles were removed at the end of the experiment and assessed histologically and biomechanically. Results. HFD feeding significantly decreased the Achilles tendon modulus without histological alterations. BCAA administration significantly decreased the stiffness of Achilles tendons in the exercised normal diet mice. Exercise partially ameliorated both the weight gain and glucose levels in the HFD-fed mice, led to a significant decrease in the maximum load of the Achilles tendon, and an increase in the average fibril diameter of the quadriceps femoris muscle. There were significant correlations between body weight and several biomechanical properties, demonstrating the importance of controlling obesity for maintaining healthy tendon properties. . Conclusions. In summary, this study showed a significant impact of obesity and body weight on tendon biomechanical properties with limited effects of exercise and BCAAs. Cite this article: Bone Joint Res 2013;2:186–92

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. Methods. This retrospective cohort study analyzed a total of 43,287 patients from national health claims data spanning 2008 to 2018, focusing on patients who underwent surgical treatment for primary Achilles tendon rupture. Short-term ATRR was defined as cases that required revision surgery occurring between six weeks and one year after the initial surgical repair, while omitting cases with simultaneous infection or skin necrosis. Variables such as age, sex, the presence of Achilles tendinopathy, and comorbidities were systematically collected for the analysis. We employed multivariate stepwise logistic regression to identify potential risk factors associated with short-term ATRR. Results. From 2009 to 2018, the short-term re-rupture rate for Achilles tendon surgeries was 2.14%. Risk factors included male sex, younger age, and the presence of Achilles tendinopathy. Conclusion. This large-scale, big-data study reaffirmed known risk factors for short-term Achilles tendon re-rupture, specifically identifying male sex and younger age. Moreover, this study discovered that a prior history of Achilles tendinopathy emerges as an independent risk factor for re-rupture, even following initial operative fixation. Cite this article: Bone Joint Res 2024;13(7):315–320

While controversy remains as to the relative benefit of operative (OM) versus non-operative management (NOM) of Achilles tendon ruptures (ATR), few studies have examined the effect on high impact maneuvers such as jumping and hopping. The purpose of this study is to compare functional performance and musculotendinous morphology in patients following OM or NOM for acute ATR. Eligible patients were aged 18-65 years old with an ATR who underwent OM or NOM within three weeks of injury and were at least one-year post injury. Gastrocnemius muscle thickness and Achilles tendon length and thickness were assessed with ultrasound. Functional performance was examined with single-leg hop tests and isokinetic plantar strength at 60o/s and 120o/s. 24 participants completed testing (12/ group). Medial (OM: 2.2 ± 0.4 cm vs 1.9 ± 0.3 cm, NOM 2.15 ± 0.5 cm vs 1.7 ± 0.5 cm; p = 0.002) and lateral (OM 1.8 ± 0.3 cm vs 1.5 ± 0.4 cm, NOM 1.6 ± 0.4 cm vs 1.3 ± 0.5 cm; p = 0.008) gastrocnemius thickness were reduced on the affected limb. The Achilles tendon was longer (OM: 19.9 ± 2.2 cm vs 21.9 ± 1.6 cm; NOM: 19.0 ± 3.7 cm vs 21.4 ± 2.9 cm; p = 0.009) and thicker (OM: 0.48 ± 0.16 cm vs 1.24 ± 0.20 cm; NOM: 0.54 ± 0.08 cm vs 1.13 ± 0.23 cm; p < 0.001) on the affected limb with no differences between groups. Affected limb plantar flexion torque at 20o plantar flexion was reduced at 60o/s (OM: 55.6 ± 20.2 nm vs 47.8 ± 18.3 nm; NOM: 59.5 ± 27.5 nm vs 44.7 ± 21.0 nm; p = 0.06) and 120o/s (OM: 44.6 ± 17.9 nm vs 36.6 ± 15.0 nm; NOM: 48.6 ± 16.9 nm vs 35.8 ± 10.7 nm; p = 0.028) with no group effect. There was no difference in single leg hop performance. Achilles tendon length explained 31.6% (p = 0.003) and 18.0% (p = 0.025) of the variance in plantar flexion peak torque limb symmetry index (LSI) at 60o/s and 120o/s respectively. Tendon length explained 28.6% (p=0.006) and 9.5% (p = 0.087) of LSI when torque was measured at 20o plantar flexion at 60o/s and 120o/s respectively. Conversely, tendon length did not predict affected limb plantar flexion peak torque (nm), angle-specific torque at 20o plantar flexion (nm) and affected limb single leg hop distance (cm) or LSI (%). There was no difference in tendon length between treatment groups and deficits in gastrocnemius thickness and strength are persistent. Deficits in the plantar flexion strength LSI are partially explained by increased tendon length following Achilles tendon rupture, regardless of treatment strategy. Hop test performance is maintained and may be the result of compensatory movements at other joints despite persistent plantarflexion weakness

Introduction and Objective. Achilles tendon defect is difficult problem for orthopedic surgeon, and therefore the development of new treatments is desirable. Platelet-rich fibrin (PRF), dense fibrin scaffold composed of a fibrin matrix containing many growth factors, is recently used as regenerative medicine preparation. However, few data are available on the usefulness of PRF on Achilles tendon healing after injury. The objective of this study is to examine whether PRF promotes the healing of Achilles tendon defect in vivo and evaluated the effects of PRF on tenocytes in vitro. Materials and Methods. PRF were prepared from rats according to international guidelines on the literature. To create rat model for Achilles tendon defect, a 4-mm portion of the right Achilles tendon was completely resected, and PRF was placed into the gap in PRF group before sewing the gap with nylon sutures. To assess the histological healing of Achilles tendon defect, Bonar score was calculated using HE, Alcian-blue, and Picosirius-red staining section. Basso, Beattie, Bresnahan (BBB) score was used for the evaluation of motor functional recovery. Biomechanical properties including failure tensile load, ultimate tensile stress, breaking elongation, and elastic modulus were measured. We examined the effects of PRF on tenocytes isolated from rat Achilles tendon in vitro. The number of viable cells were measured by MTS assay, and immunostaining of ki-67 was used for detection of proliferative cells. Migration of tenocytes was evaluated by wound closure assay. Protein or gene expression level of extracellular matrix protein, such as collagen, were evaluated by immunoblotting, immunofluorescence, or PCR. Phosphorylation level of AKT, FGF receptor, or SMAD3 was determined by western blotting. Inhibitory experiments were performed using MK-2206 (AKT inhibitor), FIIN-2 (FGFR inhibitor), SB-431542 (TGF-B receptor inhibitor), or SIS3 (SMAD3 inhibitor). All p values presented are two-sided and p values < 0.05 were considered statistically significant. Results. In rat Achilles tendon defects, Bonar score was significantly improved in PRF group compared to control group. Collagen deposition at the site of Achilles tendon defect was observed earlier in PRF group. Consistent with the histological findings, BBB score was significantly improved in PRF group. PRF also significantly improved the biomechanical properties of injured Achilles tendon. Furthermore, proliferating tenocytes, labelled by ki-67 were significantly increased in PRF group. These data suggested PRF prompted the healing of Achilles tendon defect. Thus, we further examined the effects of PRF on tenocytes in vitro. PRF significantly increased the number of viable cells, the proliferative cells labelled by ki-67, and migratory ability. Furthermore, PRF significantly increased the protein expression levels of collagen-I, collagen-III, α-SMA, and tenascin-C in tenocytes. Next, we examined the signalling pathway associated with PRF-induced proliferation of tenocytes. PRF increased the phosphorylation level and induced nuclear translocation of AKT, known as key regulator of cell survival. PRF also induced the phosphorylation of FGF receptor. Inhibition of AKT or FGF-receptor completely suppressed the positive effects of PRF on tenocytes. Furthermore, we found that inhibition of FGF receptor partially suppressed the phosphorylation of AKT by PRF. Thus, PRF induced the proliferation of tenocytes via FGFR/AKT axis. We further evaluated the signalling pathway associated with PRF-induced expression of extracellular matrix. PRF increased the phosphorylation levels of SMAD3 and induced nuclear translocation of SMAD3. Furthermore, inhibition of TGF-B receptor or SMAD3 suppressed increased expression level of extracellular matrix by PRF. Thus, PRF increased expression level of extracellular matrix protein via TGF-BR/SMAD3 axis. Conclusions. PRF promotes tendon healing of the Achilles tendon defect and recovery of exercise performance and biomechanical properties. PRF increases the proliferation ability or protein expression level of extracellular matrix protein in tenocytes via FGFR/AKT or TGF-βR/SMAD3 axis, respectively

Achilles tendon mechanical properties depend on a complex hierarchical design, with collagen being the smallest load-bearing unit. At the nanoscale, collagen molecules are organized into fibrils, which at the microscale are assembled into fibers, followed by larger structures such as sub-tendons or fascicles. Degree of in vivo loading affects the collagen content, and organization and consequently the tissue's mechanical response. We aim to unravel how composition, structural organization, and mechanical response are affected by degree of in vivo loading at each length scale. The presentation will outline the results to date about to the use of high-resolution synchrotron-based tissue characterisation methods on several length scales in combination with in situ mechanical tests. We use a rat model, where the tendons are subjected to varying loading in vivo. To characterize the tissue microstructure, phase-contrast enhanced synchrotron micro-tomography is performed. The 3D fiber organization in fully loaded tendons is highly aligned, whereas the fibers in unloaded tendons are significantly more heterogeneously arranged and crimped. To characterize the collagen fibril response, Small Angle X-ray Scattering is performed. Two types of fibril organizations are found; a single population oriented towards the main load direction and two fibril subpopulations with clearly distinct orientations. Scattering during loading showed that the fibrils in unloaded tendons did not strain as much in fully loaded. In situ loading concurrently with high resolution synchrotron experiments show the complex tendon response to in situ load and its relation to in vivo loading and tendon hierarchical structure. Unloading seems to alter the organization of the fibrils and fibers, e.g. increased crimping and more pronounced sub-tendon twists. Acknowledgements: Funding from Knut and Alice Wallenberg Foundation and European Research Council (101002516). Paul Scherrer Institut, Switzerland for beamtime at cSAXS and TOMCAT

Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

Aim. Our collaborative study aims to demonstrate that acute partial Achilles Tendon Tears (ATTs) are not separate diagnostic entities from full ATTs. and should be thought of as a continuum rather than binary partial or full. Methods. We pooled anonymised data from four hospitals, identifying patients with acute partial ATTs on USS reports from 2019–2021. Patients were only included if they had an acute injury and no previous background Achilles tendinopathy. Results. 91 patients had acute partial ATTs reported on USS. 74/91 (81%) of patients had clinical findings in keeping with a full ATT (positive Simmonds test, palpable gap). 88/91 (97%) of patients were managed according to local full ATT protocols. 2 patients had MRIs – one showed no tear, the other showed a full rupture. 2 patients underwent surgical repair and both intra-operatively were found to have full ATTs. Conclusion. Our regional data suggests that a significant proportion (81%) of USS diagnosed partial ATTs may in fact be misdiagnosed full ATTs. All injuries clinically suspicious for an ATT should be managed according to local Achilles Protocol. USS is useful to diagnose the presence or absence of a tear but is not good at differentiating partial vs full tear. There is significant tendon end fibrillation and overlap on USS of an acute full ATT, which can give the impression of a partial ATT. More research is needed into whether any threshold exists to support the current distinction of “partial” and “full” as relates to management and outcomes

Insertional Achilles tendinitis with considerable degeneration that failed non-operative treatment typically requires tendon debridement and reattachment to bone. It is common practice for tendons to be reattached back with anchor sutures, but this poses a challenge to patients who are not able to afford them. Bony anchorage of tendons may be performed by passing sutures through tunnels, but the strength of repair compared to by using anchors is not known. We investigated the load at clinical and catastrophic failure of these two methods of reattachment. Sixteen paired Achilles tendons along with the calcaneus were harvested from eight fresh frozen cadavers. Paired randomization was done. For the anchor suture group, two 5’0 anchors with polyethylene #2 sutures were used for reattachment whereas for the suture only group, tendons were reattached to bone using braided polyester #2 sutures via two bony tunnels. All samples were mounted on a materials testing system and preloaded at 50N for 60sec before load to failure at a rate of 1mm/sec. With the assumption that preloading has removed tendon crimp and any subsequent extension is a result of gapping at the repair site, loads at 5mm, 10mm, 15mm, and 20mm of extension were noted as well as the maximal load at failure. We found higher loads were needed to cause an extension of 5 to 20mm in the suture only group compared to the anchor suture group but these data were not significant. On the other hand, the anchor suture group required higher loads before catastrophic failure occurred compared to the suture only group, but this again is not significant. We conclude that suture only reattachment of the Achilles tendon is comparable in strength with anchor suture reattachment, and this method of reattachment can be considered for patients who do not have access to anchor sutures

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

The incidence of rupture of an Achilles tendon constitutes 0,01–0,02%. The infection of the Achilles tendon after operativ repair is a very rare but severe complication. In this study we examined the functional outcome after radical debridement of the Achilles tendon. From 2009 to 2014 we treated 26 patients (22 male, 4 female) with an infection oft he Achilles tendon. In 24 cases the infection was caused after suture of the tendon, in 2 cases the infection was caused by an open injury. The average age was 46,8 (21 to 75). The number of operations the patient had to undergo before admitted to our hospital was 23, in average (with an range from 0 to 9 operations). We performed a radical debridement and the insertion of a local antibiotic carrier. In all cases an at least subtotal resection of the Achilles tendon was necessary. In 10 cases we found Staphylococcus aureus, in 4 cases atleast 2 different types of bacteria. In 2 cases we detected E.coli, in 1 case Enterococcus faecalis and 1 case Bacteroides fragiles. In 6 cases we didn´t succeed in identifying a bacteria despite of a hisological report describing a severe infection. In all cases we achieved a long-lasting stop of the infection. We succeed in 22 cases with just one operation. In 2 cases we had to perform several surgeries(3 Operations and 7 operations) due to extended soft tissue damage of the lower leg and the necessity of a free flap. 22 patients are mobilized in normal shoes, 2 in orthopedic shoes. Because of the building of scartissue we didn´t find a serious impairment of the function despite a subtotal resection of the tendon. The plantar flexion was possible against resistance with reduced strength. Further operative measure such as replacement with other tendons were not required. In order o obtain a durable stop of the infection it is decisive to operate radical. All infected tissue has to be removed. Even a subtotal resection of the Achilles tendon leads to0 a satisfactory functional outcome

Introduction: Tendon lengthening is an important cause of morbidity after Achilles tendon rupture. However, direct measurement of the tendon length is difficult. Ankle dorsiflexion has therefore been used as a surrogate measure, on the assumption that it is the Achilles tendon that limits this movement. The aim of this investigation was to assess the relationship between Achilles tendon length and ankle dorsiflexion. The primary research question was whether or not the Achilles tendon is the structure that limits ankle dorsiflexion. The secondary purpose was to quantify the relationship between Achilles tendon lengthening and dorsiflexion at the ankle joint. Methods: Five cadaveric specimens were dissected to expose the tendons and capsular tissue of the leg and hindfoot. Fixed bony reference points were used as markers for the measurements. In the first specimen, the Achilles tendon was intact and the other structures that may limit ankle dorsiflexion were sequentially divided. In the other specimens the Achilles tendon was lengthened by 1cm intervals and the effect upon ankle dorsiflexion movement was recorded. Results: Division of the other tendons and the capsular tissue around the ankle joint did not affect the range of ankle dorsiflexion. When the Achilles was divided the foot could be dorsiflexed until the talar neck impinged upon the anterior aspect of the distal tibia. There was a mean increase of 12 degrees of dorsiflexion for each centimetre increase in tendon length. Conclusion: The Achilles tendon is the anatomical structure that limits ankle dorsiflexion, even when the tendon is lengthened. There was a linear relationship between the length of the Achilles tendon and the range of ankle dorsiflexion in this cadaveric model. Ankle dorsiflexion would appear to be a clinically useful indicator of tendon length

Early identification of patients at risk for impaired tendon healing and corresponding novel therapeutic approaches are urgent medical needs. This study aimed to clarify the role of CD3+ T-cells during acute Achilles tendon (AT) healing. Blood and hematoma aspirate were taken from 26 patients during AT reconstruction, and additional blood samples were obtained during clinical follow-up at 6, 26 and 52 weeks after surgery. T-cell subsets were analyzed by flow cytometry using CD3, CD4, CD8, CD11a, CD57 and CD28 antibodies. Clinical follow-up included functional tests, MRI assessments, and subjective questionnaires. In vitro, the functional behavior of patient-derived tenocytes was investigated in co-cultures with autologous unpolarized CD4+ or CD8+ T-cells, or IFNy-polarized CD8+ or IL17-polarized CD4+ Tcells (n=5-6). This included alterations in gene expression (qPCR), MMP secretion (ELISA), migration rate (scratch wound healing assay) or contractility (collagen gels). Analysis revealed that elevated CD4+ T-cell levels and reduced CD8+ T-cell levels (increased CD4/CD8 ratio) in hematoma aspirate and pre-operative blood were associated with inferior clinical outcomes regarding pain and function at 26 and 52 weeks. Increased levels of CD8+ -memory T-cell subpopulations in blood 6 weeks after surgery were associated with less tendon elongation. In vitro, tenocytes showed increased MMP1/2/3 levels and collagen III/I ratio in co-culture with unpolarized and/or IL17-polarized CD4+ T-cells compared to unpolarized CD8+ T-cells. This coincided with increased IL17 receptor expression in tenocytes co-cultured with CD4+ T-cells. Exposure of tenocytes to IL17-polarized CD4+ T-cells decreased their migration rate and increased their matrix contractility, especially compared to IFNy-polarized CD8+ T-cells. The CD4+ /CD8+ T-cell ratio could serve as prognostic marker for early identification of patients with impaired AT healing potential. Local reduction of CD4+ T-cell levels or their IL17 secretion represent a potential therapeutic approach to improve AT healing and to prevent weakening of the tendon ECM

Objectives. After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Methods. Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing. Results. Histological analysis showed well organised arrangement of collagen fibres and proteoglycan formation in the wounded ATEs in the KGN-PRP group. Furthermore, immunohistochemical analysis revealed fibrocartilage formation in the KGN-PRP-treated ATEs, evidenced by the presence of both collagen I and II in the healed ATE. Larger positively stained collagen III areas were found in both PRP and saline groups than those in the KGN-PRP group. Chondrocyte-related genes, SOX9 and collagen II, and tenocyte-related genes, collagen I and scleraxis (SCX), were also upregulated by KGN-PRP. Moreover, mechanical testing results showed higher ultimate tensile strength in the KGN-PRP group than in the saline control group. In contrast, PRP treatment appeared to have healed the injured ATE but induced no apparent formation of fibrocartilage. The saline-treated group showed poor healing without fibrocartilage tissue formation in the ATEs. Conclusions. Our results show that injection of KGN-PRP induces fibrocartilage formation in the wounded rat ATEs. Hence, KGN-PRP may be a clinically relevant, biological approach to regenerate injured enthesis effectively. Cite this article: J. Zhang, T. Yuan, N. Zheng, Y. Zhou, M. V. Hogan, J. H-C. Wang. The combined use of kartogenin and platelet-rich plasma promotes fibrocartilage formation in the wounded rat Achilles tendon entheses. Bone Joint Res 2017;6:231–244. DOI: 10.1302/2046-3758.64.BJR-2017-0268.R1

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

Surgical treatment of recurrent dislocation after total hip arthroplasty (THA) is challenging with often disappointing results. The influence of the posterior hip capsule is important, and restoration of its function is a major goal of treatment. We describe our experience using an Achilles tendon allograft as a checkrein to limit hip internal rotation and to prevent posterior instability. Twenty unstable THAs were treated using this technique, eliminating instability in fifteen. At an average follow-up of 3.6 years, Achilles tendon allograft augmentation has proven a useful adjunct for the treatment of recurrent posterior dislocation after THA in selected patients. The purpose of this study is to review our results with a novel treatment for recurrent dislocation after total hip arthroplasty (THA) using an Achilles tendon allograft as a checkrein to prevent instability. Achilles tendon allograft augmentation has proved to be a useful adjunct for the treatment of recurrent posterior dislocation after THA in selected patients. Surgical treatment of recurrent dislocation after total hip arthroplasty (THA) is challenging with often disappointing results. Among possible causes of dislocation, the influence of the static soft tissue restraint provided by the hip capsule is important, and restoration of its integrity and function is a major goal of treatment. We describe a new technique in which an Achilles tendon allograft is employed as a checkrein to limit hip internal rotation and to prevent posterior instability. Twenty unstable THAs with recurrent instability were treated using this technique, eliminating instability in fifteen at an average follow-up of 3.6 (0.5 to 6.6) years. Prospective data was collected and reviewed on the first twenty patients with recurrent THA instability stabilized with an Achilles tendon allograft. Head and liner exchanges accompanied the allograft. Use of a constrained cup was considered a failure. Instability was successfully controlled in 75% of patients with use of the Achilles allograft. The technique is an important addition to the treatment arsenal of this difficult problem

Tendon healing is a complex process that often results in compromised healing of the tendon tissue. It has recently been shown that temporal changes in the expression profile and the histological tissue quality of the tendons occur during the early healing process after acute Achilles tendon rupture. Whether these changes are accompanied by an altered healing process, is not yet known and was the aim of the present study. Tendon biopsies were obtained from 24 patients with acute Achilles tendon rupture at the time of surgery (2–9 days after rupture) and examined histologically as well as on RNA level. Histologically, the tendon architecture, the amount of aligned collagen, glycosaminoglycan and fat as well as the cellularity, vascularity and immune cell infiltration were determined. On RNA level the expression of markers for the modeling/remodeling (MMPs and TIMPs), collagens (1, 3, 5), tendon markers (scleraxis, tenomodulin), pro- and anti-inflammatory markers (IL-1beta, IL6, IL10, IL33, TNFa, TGF-beta1, COX2) and immune cell markers (CD3, CD68, CD80, CD206) were analyzed by Real-Time PCR. To determine the clinical outcome, the patients were followed up 12 months after the operation and the following scores were recorded: Subjective score, Tegner score, Visual Analog Scale (VAS) pain, VAS function, Matles Test, Achilles tendon total rupture score (ATRS), Therman 100-points score, Heel rise test. Statistics: Spearman correlation analysis. Correlation analysis shows that early post-rupture surgery is associated with better clinical outcome (ATRS Score: p=0.022). Histologically, a good functional healing outcome shows a positive correlation to the amount of aligned collagen (Heel Rise Test: p = 0.009) and glycosaminoglycans in the tendon (Heel Rise Test: p = 0.026, Matles difference: p = 0.029), as well as a negative correlation to the fat content (Thermann score: p = 0.018, subjective score: p = 0.027, VAS function: p = 0.031). On RNA level, a good healing outcome correlates with increased expression of MMP13, collagen 1, 3, 5 (Heel Rise Test: p = 0.019, p = 0.048, p = 0.030), and TIMP2 (Tegner Score: p = 0.040), TGF-beta1 (Thermann Score: p = 0.032) and CD80 (ATRS: p = 0.025, Thermann score:, p = 0.032). Whereas a limited healing outcome is associated with an increased expression of MMP2 (Heel Rise Test: p = 0.033), MMP3 (Matles Test: p=0.001, Heal Rise test p = 0.017), and IL33 (Tegner Score: p = 0.047). The results of the study show a clear relationship between the tendon biology at the time of the surgery and the clinical and functional healing outcome 12 months after the operation. Especially matrix formation and remodeling play a crucial role, while the examined immunological factors seem to influence the tendon healing to a lesser extent. The modulation of matrix formation could potentially lead to improved treatment options in the future

Introduction. Growing evidence in the literature suggests better clinical and functional outcomes and lower re-rupture rates with repair compared to non-operative treatment of ruptured Achilles tendon. There are however, concerns of wound infection, nerve injury and scar tenderness with the standard open and percutaneous techniques of repair. We aim to evaluate clinical and functional outcomes and complications in patients treated with minimally invasive Achillon device. Materials and Methods. Prospectively collected clinical data was reviewed of all consecutive patients who underwent repair of the ruptured Achilles tendon using the Achillon device. Patients were contacted using a postal questionnaire for assessment of their functional status using the validated Achilles Tendon Total Rupture Score (ATRS) and compared with their uninjured side. The outcomes were compared to the published results. Results. We present patient demographics; and clinical and functional outcomes of 140 consecutive patients who underwent repair of ruptured Achilles tendon using the minimally invasive technique between June 2007 to August 2010. Our complication rate was of two-three percent each of proximal DVT, scar sensitivity, superficial wound infection and no re-rupture after a minimum of 6 months. There was no case of nerve injury leading to permanent neurological deficit. Discussion. This study demonstrates good clinical and functional outcomes from using the Achillon device in repair of ruptured Achilles tendon with a low complication rate comparable to other published series. We recommend Achillon device as a safe minimally invasive technique for repair of the ruptured Achilles tendon

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