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

Aims. Avulsion of the proximal hamstring tendon origin can result in significant functional impairment, with surgical re-attachment of the tendons becoming an increasingly recognized treatment. The aim of this study was to assess the outcomes of surgical management of proximal hamstring tendon avulsions, and to compare the results between acute and chronic repairs, as well as between partial and complete injuries. Methods. PubMed, CINAHL, SPORTdiscuss, Cochrane Library, EMBASE, and Web of Science were searched. Studies were screened and quality assessed. Results. In all, 35 studies (1,530 surgically-repaired hamstrings) were included. Mean age at time of repair was 44.7 years (12 to 78). A total of 846 tears were acute, and 684 were chronic, with 520 tears being defined as partial, and 916 as complete. Overall, 92.6% of patients were satisfied with the outcome of their surgery. Mean Lower Extremity Functional Score was 74.7, and was significantly higher in the partial injury group. Mean postoperative hamstring strength was 87.0% of the uninjured limb, and was higher in the partial group. The return to sport (RTS) rate was 84.5%, averaging at a return of 6.5 months. RTS was quicker in the acute group. Re-rupture rate was 1.2% overall, and was lower in the acute group. Sciatic nerve dysfunction rate was 3.5% overall, and lower in the acute group (p < 0.05 in all cases). Conclusion. Surgical treatment results in high satisfaction rates, with good functional outcomes, restoration of muscle strength, and RTS. Partial injuries could expect a higher functional outcome and muscle strength return. Acute repairs result in a quicker RTS with a reduced rate of re-rupture and sciatic nerve dysfunction. Cite this article: Bone Jt Open 2022;3(5):415–422

Aims. A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results. Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion. More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons. Cite this article: Bone Jt Open 2023;4(8):628–635

Tendons display poor intrinsic healing properties and are difficult to treat[1]. Prior in vitro studies[2] have shown that, by targeting the Activin A receptor with magnetic nanoparticles (MNPs), it is possible to remotely induce the tenogenic differentiation of human adipose stem cells (hASCs). In this study, we investigated the tenogenic regenerative potential of remotely-activated MNPs-labelled hASCs in an in vivo rat model. We consider the potential for magnetic controlled nanoparticle mediated tendon repair strategies. hASCs were labelled with 250 nm MNPs functionalized with anti-Activin Receptor IIA antibody. Using a rapid curing fibrin gel as delivery method, the MNPs-labelled cells were delivered into a Ø2 mm rat patellar tendon defect. The receptor was then remotely stimulated by exposing the rats to a variable magnetic gradient (1.28T), using a customised magnetic box. The stimulation was performed 1 hour/day, 3 days/week up to 8 weeks. Tenogenesis, iron deposition and collagen alignment were assessed by histological staining and IHC. Inflammation mediators levels were assessed by ELISA and IHC. The presence of human cells in tendons after 4 and 8 weeks was assessed by FISH analysis. Histological staining showed a more organised collagen arrangement in animals treated with MNPs-labelled cells compared to the controls. IHC showed positive expression of tenomodulin and scleraxis in the experimental groups. Immunostaining for CD45 and CD163 did not detect leukocytes locally, which is consistent with the non-significant levels of the inflammatory cytokines analysis performed on plasma. While no iron deposition was detected in the main organs or in plasma, the FISH analysis showed the presence of human donor cells in rat tendons even after 8 weeks from surgery. Our approach demonstrates in vivo proof of concept for remote control stem cell tendon repair which could ultimately provide injectable solutions for future treatment. We are grateful for ERC Advanced Grant support ERC No.789119, ERC CoG MagTendon No.772817 and FCT grant 2020.01157.CEECIND

Depletion of Scleraxis-lineage (ScxLin) cells in adult tendon recapitulates age-related decrements in cell density, ECM organization and composition. However, depletion of ScxLin cells improves tendon healing, relative to age-matched wildtype mice, while aging impairs healing. Therefore, we examined whether ScxLin depletion and aging result in comparable shifts in the tendon cell environment and defined the intrinsic programmatic shifts that occur with natural aging, to define the key regulators of age-related healing deficits. ScxLin cells were depleted in 3M-old Scx-Cre+; Rosa-DTRF/+ mice via diphtheria toxin injections into the hindpaw. Rosa-DTRF/+ mice were used as wildtype (WT) controls. Tendons were harvested from 6M-old ScxLin depleted and WT mice, and 21-month-old (21M) C57Bl/6 mice (aged). FDL tendons (n=6) were harvested for single-cell RNAseq, pooled, collagenase digested, and sorted for single cell capture. Data was processed using Cell Ranger and then aligned to the annotated mouse genome (mm10). Filtering, unsupervised cell clustering, and differential gene expression (DEG) analysis were performed using Seurat. Following integration and sub-clustering of the tenocyte populations, five distinct subpopulations were observed. In both ScxLin depletion and aging, ‘ECM synthesizers’ and ‘ECM organizers’ populations were lost, consistent with disruptions in tissue homeostasis and altered ECM composition. However, in ScxLin depleted mice retention of a ‘specialized ECM remodeler’ population was observed, while aging tendon cells demonstrated inflammatory skewing with retention of a ‘pro-inflammatory tenocyte population’. In addition, enrichment of genes associated with protein misfolding clearance were observed in aged tenocytes. Finally, a similar inflammatory skewing was observed in aged tendon-resident macrophages, with this skewing not observed in ScxLin depleted tendons. These data suggest that loss of ‘ECM synthesizer’ populations underpins disruptions in tendon homeostasis. However, retention of ‘specialized remodelers’ promotes enhanced healing (ScxLin depletion), while inflammatory skewing may drive the impaired healing response in aged tendons

Aims. The Chopart joint complex is a joint between the midfoot and hindfoot. The static and dynamic support system of the joint is critical for maintaining the medial longitudinal arch of the foot. Any dysfunction leads to progressive collapsing flatfoot deformity (PCFD). Often, the tibialis posterior is the primary cause; however, contrary views have also been expressed. The present investigation intends to explore the comprehensive anatomy of the support system of the Chopart joint complex to gain insight into the cause of PCFD. Methods. The study was conducted on 40 adult embalmed cadaveric lower limbs. Chopart joint complexes were dissected, and the structures supporting the joint inferiorly were observed and noted. Results. The articulating bones exhibit features like a cuboid shelf and navicular beak, which appear to offer inferior support to the joint. The expanse of the spring ligament complex is more medial than inferior, while the superomedial part is more extensive than the intermediate and inferoplantar parts. The spring ligament is reinforced by the tendons in the superomedial part (the main tendon of tibialis posterior), the inferomedial part (the plantar slip of tibialis posterior), and the master knot of Henry positioned just inferior to the gap between the inferomedial and inferoplantar bundles. Conclusion. This study highlights that the medial aspect of the talonavicular articulation has more extensive reinforcement in the form of superomedial part of spring ligament and tibialis posterior tendon. The findings are expected to prompt further research in weightbearing settings on the pathogenesis of flatfoot. Cite this article: Bone Jt Open 2024;5(4):335–342

Objectives. Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery. Methods. A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs). Results. Failed-repair stump tissue showed cellular accumulation of crumpled and disoriented collagen fibres. Compared with normal tendon, stump tissue had significantly higher gene expression of collagens I and III, matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF). The stump TDSCs presented both mesenchymal stem and haematopoietic cell markers with significantly increased expression of CD34, CD44, and CD90 markers. Stump TDSCs exhibited similar migration but a lower proliferation rate, as well as similar osteogenic differentiation but a lower chondrogenic/adipogenic differentiation capability, compared with normal TDSCs. Stump TDSCs also showed increasing levels of SRY-box 2 (Sox2), octamer-binding transcription factor 4 (Oct4), tenomodulin (TNMD), and scleraxis (Scx) protein and gene expression. Conclusion. We found that a failed repair stump had increased cellularity that preserved both mesenchymal and haematopoietic stem cell characteristics, with higher collagen synthesis, MMP, and growth factor gene expression. This study provides evidence that tendon stump tissue has regenerative potential. Cite this article: C-C. Lu, T. Zhang, R. L. Reisdorf, P. C. Amadio, K-N. An, S. L. Moran, A. Gingery, C. Zhao. Biological analysis of flexor tendon repair-failure stump tissue: A potential recycling of tissue for tendon regeneration. Bone Joint Res 2019;8:232–245. DOI: 10.1302/2046-3758.86.BJR-2018-0239.R1

Decellularised porcine superflexor tendon (pSFT) has been demonstrated to be a suitable scaffold for anterior cruciate ligament reconstruction[1]. While the role of collagen in tendons is well known, the mechanical role of glycosaminoglycans (GAGs) is less clear and may be altered by the decellularisation process. To determine the effects of decellularisation on pSFT GAG content and mechanical function and to investigate the consequences of GAG loss in tensile and compressive loading. pSFTs were decellularised following previous techniques [2]. For GAG removal, native pSFTs were treated with chondroitinase ABC (ChABC; 0.1U/mL, 72h). Cell and GAG removal was validated using histology and quantitative assays. Native, decellularised and ChABC treated groups (n=6) were biomechanically characterised. In tension, specimens underwent stress relaxation and strength testing using previous protocols [1]. Stress relaxation data was fitted to a modified Maxwell-Weichert model to determine time-dependent (E1 & E2) and time-independent moduli (E0). The toe and linear region moduli (Etoe, Elinear), in addition to tensile strength (UTS) and failure strain were determined from strength testing. In compression, specimens underwent confined loading conditions (ramp at 10 s-1 to 10% strain and hold). The aggregate modulus (HA) and zero-strain permeability (k0) were determined using previous techniques [3]. Data was analysed by one-way ANOVA with Tukey post-hoc test to determine significant differences between test groups (p<0.05). Quantitative assays showed no GAG reduction post-decellularisation, but a significant reduction after ChABC treatment. HA was only significantly reduced in the ChABC group. k0 was significantly higher for the ChABC group compared to decellularised. E0 was significantly reduced in the decellularised group compared to native and ChABC groups, while E1 and E2 were not different between groups. Etoe, Elinear, UTS and failure strain were not different between groups. Decellularisation does not affect GAG content or impair mechanical function in pSFT. GAG loss adversely affects pSFT compressive properties, revealing major mechanical contribution under compression, but no significant role under tension

Aims. To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods. Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 10. 6. ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results. In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion. ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786

There is a growing socio-economic need (i.e. “ageing society”) for effective and reproducible strategies to repair musculoskeletal tissue. In particular, acute tendon injury and chronic tendinopathies remain clinically challenging and novel treatment modalities are urgently needed. Tendons resemble a connective tissue rich in highly organized collagen fibers, displaying a remarkably high tensile strength. However, partly due to the low number of cells and their more or less avascular nature tendons heal relatively slowly. Ultimately, tendon regeneration encompasses the full restoration of the biological, biochemical and biomechanical properties, which are often impaired by endogenous healing cascades. Usually, a connective scar tissue forms at the injury site and the replaced tissue does not function adequately at high strain levels, increasing the chance of re-rupture. Despite significant advancements in tissue regeneration and engineering strategies, the clinical impact for the regeneration of tendon remains limited. For the development of novel methods to repair tendons we need to pin down the molecular and cellular mechanisms amenable to modulate endogenous (or exogenous) cell behaviour towards functional tissue regeneration. By comparing the gene expression profile of Achilles tendon tissue harvested from young-mature and old mice we demonstrate profound changes in the expression of ECM-related proteins and a previously unknown role of Secreted protein acidic and rich in cysteine (Sparc; also known as BM-40 or osteonectin) in tendons. Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties potentially drives adipogenic differentiation of tendon stem and progenitor cells (TDSPCs) and consequently lipid accretion in tendons. Generally, the fate of stem/ progenitor cells is largely determined by stimuli from the stem cell niche. In tendons, we describe a novel cellular barrier, most likely preventing the leakage of blood-borne products into the tendon proper. We propose that this “blood-tendon barrier” is part of the stem cell niche in tendons controlling TDSCP fate, preventing erroneous differentiation. By investigating the developmental programs driving tendon tissue formation and on the other hand the mechanisms contributing to the senescence of tendons, ultimately resulting in decreased quality of tendons in the elderly, novel targets for clinical intervention potentially can be discovered

The April 2023 Wrist & Hand Roundup. 360. looks at: MRI-based classification for acute scaphoid injuries: the OxSMART; Deep learning for detection of scaphoid fractures?; Ulnar shortening osteotomy in adolescents; Cost-utility analysis of thumb carpometacarpal resection arthroplasty; Arthritis of the wrist following scaphoid fracture nonunion; Extensor hood injuries in elite boxers; Risk factors for reoperation after flexor tendon repair; Nonoperative versus operative treatment for displaced finger metacarpal shaft fractures

Tendons mainly consist of collagen in order to withstand high tensile forces. Compared to other, high turnover tissues, cellularity and vascularity in tendons are low. Thus, the natural healing process of tendons takes long and can be problematic. In case of injury to the enthesis, the special transition from tendon over cartilage to bone is replaced by a fibrous scar tissue, which remains an unsolved problem in rotator cuff repair. To improve tendon healing, many different approaches have been described using scaffolds, stem cells, cytokines, blood products, gene therapy and others. Despite promising in vitro and in vivo results, translation to patient care is challenging. In clinics however, tendon auto- or allografts remain still first choice to augment tendon healing if needed. Therefore, it is important to understand natural tendon properties and natural tendon healing first. Like in other tissues, senescence of tenocytes seems to play an important role for tendon degeneration which is interestingly not age depended. Our in vivo healing studies have shown improved and accelerated healing by adding collagen type I, which is now used in clinics, for example for augmentation of rotator cuff repair. Certain cytokines, cells and scaffolds may further improve tendon healing but are not yet used routinely, mainly due to missing clinical data, regulatory issues and costs. In conclusion, the correct diagnosis and correct first line treatment of tendon injuries are important to avoid the necessity to biologically augment tendon healing. However, strategies to improve and accelerate tendon healing are still desirable. New treatment opportunities may arise with further advances in tendon engineering in the future

During aging, tendons demonstrate substantial disruptions in homeostasis, leading to impairments in structure-function. Impaired tendon function contributes to substantial declines quality of life during aging. Aged tendons are more likely to undergo spontaneous rupture, and the healing response following injury is impaired in aged tendons. Thus, there is a need to develop strategies to maintain tendon homeostasis and healing capacity through the lifespan. Tendon cell density sharply declines by ∼12 months of age in mice, and this low cell density is retained in geriatric tendons. Our data suggests that this decline in cellularity initiates a degenerative cascade due to insufficient production of the extracellular matrix (ECM) components needed to maintain tendon homeostasis. Thus, preventing this decline in tendon cellularity has great potential for maintaining tendon health. Single cell RNA sequencing analysis identifies two changes in the aged tendon cell environment. First, aged tendons primarily lose tenocytes that are associated with ECM biosynthesis functions. Second, the tenocytes that remain in aged tendons have disruptions in proteostasis and an increased pro-inflammatory phenotype, with these changes collectively termed ‘programmatic skewing'. To determine which of these changes drives homeostatic disruption, we developed a model of tenocyte depletion in young animals. This model decreases tendon cellularity to that of an aged tendon, including decreased biosynthetic tenocyte function, while age-related programmatic skewing is absent. Loss of biosynthetic tenocyte function in young tendons was sufficient to induce homeostatic disruption comparable to natural aging, including deficits in ECM organization, composition, and material quality, suggesting loss biosynthetic tenocytes as an initiator of tendon degeneration. In contrast, our data suggest that programmatic skewing underpins impaired healing in aged tendons. Indeed, despite similar declines in the tenocyte environment, middle-aged and young-depleted tendons mount a physiological healing response characterized by robust ECM synthesis and remodeling, while aged tendons heal with insufficient ECM

Introduction. Patients with hip abductor tendon tears amenable to endoscopic repair tend to be severely disabled and older. However, low preop baseline patient reported outcome (PRO) and advancing age are each often reported to be a harbinger of poor result with hip arthroscopy. Thus, the purpose of this study is to report the demographic makeup of this population and how these patients faired in terms of preop scores and reaching both Minimal Clinically Important Difference (MCID) and Substantial Clinical Benefit (SCB). Methods. Sixty-six consecutive hips in 64 patients (2 bilateral) undergoing endoscopic abductor tendon repair with a hollow core bioabsorbable suture anchor and having achieved two-year follow-up were prospectively assessed with modified Harris Hip Score (mHHS) and international Hip Outcome Tool (iHOT) scores. The MCID for patients undergoing hip arthroscopy has previously been determined as 8 for the mHHS and 13 for the iHOT. SCB has been determined as 20 for the mHHS and 28 for the iHOT. Subgroups were compared using the independent samples t-test. Results. The average age was 57 years (range 22–83 years) with 59 females and 5 males. Post-operative follow-up averaged 28 months (range 24–60). There were 33 full-thickness and 33 partial-thickness tears; 39 gluteus medius tears, 25 medius and minimus tears, and 2 isolated minimus tears. Among the 66 hips, the average preop mHHS was 48.8 with 98.5% achieving MCID and 93.8% SCB. Among 60 hips that had complete iHOT data, the average preop score was 30.0 with 98.3% achieving MCID and 88.3% SCB. There were no complications. One patient underwent repeat arthroscopy for joint debridement at 12 months following abductor repair, and one subsequently underwent total hip replacement at 11 months following repair. There was no statistically significant difference between subgroups of full thickness/partial thickness tears, or single/two tendon tears. Conclusion. This report of endoscopic abductor tendon repair represents a heterogeneous group of single and two tendon involvement with partial and full thickness tears. Collectively these patients can respond exceptionally well in terms of MCID (98.5% mHHS; 98.3% iHOT) and SCB (93.8% mHHS; 88.3% iHOT), even in the presence of low preop baseline scores (average 48.8 mHHS; 30 iHOT) and older age (average 57 years). For any tables or figures, please contact the authors directly

Tendon injuries after distal radius fractures Introduction: Tendon injuries after distal radius fractures are a well-documented complication that can occur in fractures managed both operatively and non-operatively. The extensor tendons, in particular the extensor pollicis longus (EPL) tendon, can be damaged and present late after initial management in a cast, or by long prominent screws that penetrate the dorsal cortex and cause attrition. Similarly, a prominent or distally placed volar plate can damage the flexor pollicis longus tendon (FPL). The aim of our study was to evaluate the incidence of tendon injuries associated with distal radius fractures. We conducted a single centre prospective observational study. Patients aged 18–99 who presented with a distal radius fracture between May 2018 to April 2020 were enrolled and followed-up for 24 months. Tendon injuries in the group were prospectively evaluated. Results: 199 patients with distal radius fractures were enrolled. 119 fractures (59.8%) had fixation and 80 (40.2%) were managed incast. In the non-operative group, 2 (2.5%) had EPL ruptures at approximately 4 weeks post injury. There were no extensor tendon ruptures in the operative group. In the operative group, there were 6 (5%) patients that required removal of metalware for FPL irritation. At the time of operation, there were no tendon ruptures noted. Within the operative group we evaluated plate prominence using a previously described classification (Soong et al.). 5 of the 6 patients (83%) with FPL irritation had Grade 3 prominence. The incidence of both flexor and extensor tendon injury in our cohort was 4%, extensor tendon rupture was 1% and flexor tendon rupture was avoided by early metalware removal. This study demonstrates tendon injuries are not uncommon after distal radius fractures, and close examination and follow-up are necessary to prevent eventual rupture. Plate prominence at the time of fixation should be minimised to reduce the risk of rupture

Aims. The aim of this study is to provide a detailed description of cases combining bridging patch repair with artificial ligament “internal brace” reinforcement to treat irreparable massive rotator cuff tears, and report the preliminary results. Methods. This is a retrospective review of patients with irreparable massive rotator cuff tears undergoing fascia lata autograft bridging repair with artificial ligament “internal brace” reinforcement technique between January 2017 and May 2018. Inclusion criteria were: patients treated arthroscopically for an incompletely reparable massive rotator cuff tear (dimension > 5 cm or two tendons fully torn), stage 0 to 4 supraspinatus fatty degeneration on MRI according to the Goutallier grading system, and an intact or reparable infraspinatus and/or subscapularis tendon of radiological classification Hamada 0 to 4. The surgical technique comprised two components: first, superior capsular reconstruction using an artificial ligament as an “internal brace” protective device for a fascia lata patch. The second was fascia lata autograft bridging repair for the torn supraspinatus. In all, 26 patients with a mean age 63.4 years (SD 6.2) were included. Results. All patients underwent more than two years of follow-up (mean 33.5 months (24 to 45)). All clinical scores were also improved at two-year follow-up (mean visual analogue scale 0.7 (SD 0.5) vs 6.1 (SD 1.2); p < 0.001; mean American Shoulder and Elbow Surgeons score 93.5 (SD 5.3) vs 42.5 (SD 10.8); p < 0.001; mean University of California, Los Angeles score, 31.7 (SD 3.7) vs 12.0 (SD 3.1); p < 0.001; and mean Constant-Murley score 88.7 (SD 3.5) vs 43.3 (SD 10.9); p < 0.001), and 24 of 26 fascia lata grafts were fully healed on MRI (92%). One patient had haematoma formation at the harvesting side of the fascia lata at two days postoperatively. Conclusion. The fascia lata autograft bridging repair combined with artificial ligament internal brace reinforcement technique achieved good functional outcomes, with a high rate of graft healing at two-year follow-up. Although the short-term results are promising, further studies with a greater number of patients would provide clearer results. Cite this article: Bone Joint J 2021;103-B(10):1619–1626

Tendons are characterised by an inferior healing capacity when compared to other tissues, ultimately resulting in the formation of a pathologically altered extracellular matrix structure. Although our understanding of the underlying causes for the development and progression of tendinopathies remains incomplete, mounting evidence indicates a coordinated interplay between tendon-resident cells and the ECM is critical. Our recent results demonstrate that the matricellular protein SPARC (Secreted protein acidic and rich in cysteine) is essential for regulating tendon tissue homeostasis and maturation by modulating the tissue mechanical properties and aiding in collagen fibrillogenesis [1,2]. Consequently, we speculate that SPARC may also be relevant for tendon healing. In a rat patellar tendon window defect model, we investigated whether the administration of recombinant SPARC protein can modulate tendon healing. Besides the increased mRNA expression of collagen type 1 and the downregulation of collagen type 3, a robust increase in the expression of pro-regenerative fibroblast markers in the repair tissue after a single treatment with rSPARC protein was observed. Additionally, pro-fibrotic markers were significantly decreased by the administration of rSPARC. Determination of structural characteristics was also assessed, indicating that the ECM structure can be improved by the application of rSPARC protein. Therefore, we believe that SPARC plays an important role for tendon healing and the application of recombinant SPARC to tendon defects has great potential to improve functional tendon repair

Olecranon plates used for the internal fixation of complex olecranon fractures are applied directly over the triceps tendon on the posterior aspect of the olecranon. The aim of the study is to describe the relationship of the plates and screws to the triceps tendon at the level of the olecranon. Eight cadaveric elbows were used. Dimensions of the triceps tendon at the insertion and 1cm proximal were measured. A long or a short olecranon plate was then applied over the olecranon and the most proximal screw applied. The length of the plate impinging on the tendon and the level of the screw tract on the tendon and bone were measured. The mean olecranon height was 24.3cm (22.4-26.9cm) with a tip-to-tendon distance of 14.5cm (11.9-16.2cm). The triceps tendon footprint averaged 13.3cm (11.7-14.9cm) and 8.8cm (7.6-10.2cm) in width and length, respectively. The mean width of the central tendon 1 cm proximal to the footprint was 6.8 cm. The long olecranon plate overlay over more movable tendon length than did the short plate and consequently the superior screw pierced the triceps tendon more proximally with the long plate. Using the Mann-Whitney U test, the differences were significant. The long olecranon plates encroach on more triceps tendon than short plates. This may be an important consideration for olecranon fractures with regards implant loosening or triceps tendon injury

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers. Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations. In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels. PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation. Acknowledgments: The authors acknowledge the Biotechnology and Biological Sciences Research Council (BB/W007282/1) for funding this work

Introduction. Hip abductor tendon tears have been referred to as “rotator cuff tears of the hip,” and are a recognized etiology for persistent, often progressive, lateral hip pain, weakness, and limp. Multiple repair techniques and salvage procedures for abductor tendon tears have been reported in the literature; however, re-tear remains a frequent complication following surgical repair. This study compares the short-term outcomes of open abductor tendon repairs with decortication and suture fixation (DSF) compared to a modified technique repair into a bone trough (BT), to determine best surgical results for large abductor tendon avulsions. Additionally, surgical treatment of small tears versus large tears was examined. Methods. The outcomes of 37 consecutive hip abductor tendon repairs treated between January 2009 and December 2017 were retrospectively reviewed. Large tears were defined as detachment of 33–100% of the gluteus medius insertion. There were 15 DSF and 10 BT cases. Postoperative pain, ability to perform single leg stance, hip abduction, and Trendelenburg lurch, were examined. Small tears (12 cases) were defined as having no gluteus medius avulsion from the trochanteric insertion and were comprised of longitudinal tears (repaired side-by-side) and isolated gluteus minimus tears (repaired by tenodesis to the overlying gluteus medius). Standard statistical analyses were utilized. Type I error for all analyses was set at α=0.05. Results. When comparing large tear repair outcomes, repairs into a BT had superior outcomes to repairs with DSF: 0 (BT) versus 6 (DSF, 40%) failure rate (p<0.05), and greater reductions in pain at one-year post surgery (Δ VAS: BT, −5.70±0.97 | DSF: −2.73±0.69; p<0.01), ability to perform a single leg stance and hip abduction (90% and 100% vs 47% and 73%) (p<0.05). Clinical strength ratings were higher for repairs into a BT, but this did not reach statistical significance. When comparing large to small tear repair outcomes, small tears were found to have lower VAS pain scores and higher clinical strength ratings during both the pre-op and 1-year post-op time points (p<0.05). A higher percentage of those with small tears were able to perform a single leg stance and hip abduction (100%) compared to those with large tears (64% and 78% respectively) (p<0.05). A significantly higher frequency of residual lurch was also observed for those with large tears; 56% compared to small tears at 0%. Conclusions. Utilizing a BT repair significantly improved surgical results for large abductor tendon avulsions. Level of evidence: Therapeutic level IV case series

Tendinopathy is the most common form of chronic tendon disorders, accounting for up 30% of all musculoskeletal clinic visits [1]. In tendon disease, the largely avascular tendon tissue often becomes hypervascularized and fibrotic [2]. As blood vessel growth and angiogenic signaling molecules are often induced by the lack of adequate nutrients and oxygen, hypoxic signaling is speculated to be a root cause of tendon neovascularization and tendinopathy [3,4,5]. However, how the vascular switch is initiated in tendons, and how vascularization contributes to tendon pathology remains unknown. In this talk, we provide evidence that HIF-1α is implicated in tendon disease and HIF-1α stabilization in human tendon cells induces vascular recruitment of endothelial cells via VEGFa secretion. More interesting, HIF-1α stabilization in tendon cells in vivo, seems to recapitulate all main features of fibrotic human tendon disease, including vascular ingrowth, matrix disorganization, changes in tissue mechanics, cell proliferation and innervation. Surprisingly, in vivo knock-out of VEGFa rescued angiogenesis in the tendon core but it did not affect tendon mechanical properties and tissue pathophysiological changes, suggesting that blood vessels ingrowth might not be a primary cause but a consequence of HIF-1α activation

Tendon injuries occur frequently in athletes and the general population, with inferior healing leading to deposition of fibrotic scar tissue. New treatments are essential to limit fibrosis and enable tendon regeneration post-injury. In this study, we tested the hypothesis that rapamycin improves tendon repair and limits fibrosis by inhibiting the mTOR pathway. The left hindlimb of female adult Wistar rats was injured by needle puncture and animals were either given daily injections of rapamycin (2mg/kg) or vehicle. Animals were euthanized 1 week or 3 weeks post-injury (n=6/group). Left and right Achilles tendons were harvested, with the right limbs acting as controls. Tendon sections were stained with haematoxylin & eosin, and scored by 2 blinded scorers, assessing alterations in cellularity, cell morphology, vascularity, extracellular matrix (ECM) organization and peritendinous fibrosis. Immunohistochemistry was performed for the tendon pan-vascular marker CD146 and the autophagy marker LC3. Injury resulted in significantly altered ECM organization, cell morphology and cellularity in both rapamycin and vehicle-treated groups, but no alterations in vascularity compared to uninjured tendons. Rapamycin had a limited effect on tendon repair, with a significant reduction in peritendinous fibrosis 3 weeks after injury (p=0.028) but no change in cell morphology, cellularity or ECM organization compared to vehicle treated tendons at either 1 week or 3 weeks post injury. CD146 labelling was increased at the site of injury, but there was no apparent difference in CD146 or LC3 labelling in rapamycin and vehicle treated tendons. The decrease in peritendinous fibrosis post-injury observed in rapamycin treated tendons indicates rapamycin as a potential therapy for tendon adhesions. However, the lack of improvement of other morphological parameters in response to rapamycin treatment indicates that rapamycin is not an effective therapy for injuries to the tendon core. Acknowledgements: This study was funded by Versus Arthritis (22607)

As high incidences of tendinopathies are observed particularly in those who intensively use their tendons, we assume that pathological changes are caused, at least partially, by mechanical overload. This has led to the so-called overload hypothesis, explaining the development of tendinopathies by structural failure resulting from excessive load. At the same time, tendon loading is an important part in tendon rehabilitation. Currently, exercise treatment approaches such as eccentric training or heavy load resistance training are widely applied in tendinopathy rehabilitation, with good clinical results such as an improvement in function and a reduction in pain. Particularly those rehabilitative approaches which impose high strains on the tendon may induce an adaptation of the tendon's mechanical properties such as increased tendon stiffness. An increased tendon stiffness is often interpreted as desirable, as it may protect the tendon from overloading and thus prevent future strain injuries. However, the tendinopathic tendon is not necessarily less stiff than the tendon in the contralateral leg and an improvement in tendon stiffness is not necessarily accompanied by an improvement in tendon pain or function. In addition, metabolic factors, resulting e.g. in low-level systemic inflammation, may contribute to pathological tendon tissue changes and are not necessarily affected by an exercise program, while nutritional interventions or dietary supplements may potentially affect tendon cell metabolism. Indeed, dietary supplements have been introduced as an additional therapeutic approach in the treatment of tendinopathies in recent years, and their positive curative effects have been reported for both the general population and athletes. In the management of tendinopathies, it may thus be advisable if therapeutic approaches aim to address both tendon mechanics and tendon metabolism for better treatment effectiveness and a sustainable improvement in pain and function

Extracellular matrix (ECM) mechanical cues guide healing in tendons. Yet, the molecular mechanisms orchestrating the healing processes remain elusive. Appropriate tissue tension is essential for tendon homeostasis and tissue health. By mapping the attainment of tensional homeostasis, we aim to understand how ECM tension regulates healing. We hypothesize that diseased tendon returns to homeostasis only after the cells reach a mechanically gated exit from wound healing. We engineered a 3D mechano-culture system to create tendon-like constructs by embedding patient-derived tendon cells into a collagen I hydrogel. Casting the hydrogel between posts anchored in silicone allowed adjusting the post stiffness. Under this static mechanical stimulation, cells remodel the (unorganized) collagen representing wound healing mechanisms. We quantified tissue-level forces using post deflection measurements. Secreted ECM was visualized by metabolic labelling with non-canonical amino acids, click chemistry and confocal microscopy. We blocked cell-mediated actin-myosin contractility using a ROCK inhibitor (Y27632) to explore the involvement of the Rho/ROCK pathway in tension regulation. Tissue tension forces reached the same homeostatic level at day 21 independent of post compliance (p = 0.9456). While minimal matrix was synthesized in early phases of tissue formation (d3-d5), cell-deposited ECM was present in later stages (d7-d9). More ECM was deposited by tendon constructs cultured on compliant (1Nm) compared to rigid posts (p = 0.0017). Matrix synthesized by constructs cultured on compliant posts was less aligned (greater fiber dispersion, p = 0.0021). ROCK inhibition significantly decreased tissue-level tensional forces (p < 0.0001). Our results indicate that tendon cells balance matrix remodeling and synthesis during tissue repair to reach an intrinsically defined “mechanostat setpoint” guiding tension-mediated exit from wound healing towards homeostasis. We are identifying specific molecular mechanosensors governing tension-regulated healing in tendon and investigate the Rho/ROCK system as their possible downstream pathway

Tissue engineering and regenerative medicine (TERM) hold the promise to provide therapies for injured tendons despite the challenging cues of tendon niche and the lack of specific factors to guide regeneration. The emerging potential of magnetic responsiveness and magnetic nanoparticles (MNPs) functionalities offers new perspectives to tackle TERM challenges. Moreover, pulsed electromagnetic field (PEMF) is FDA approved for orthopaedics with potential to control inflammation upon injury. We previously demonstrated that magnetic cell-sheets assisted by PEMF trigger the inflammation resolution by modulating cytokine-enriched environments [1]. To further understand the potential of magnetically assisted living patches, we have recently conducted in vivo studies using a rat patellar defect model. After labeling of human adipose stem cells with iron oxide MNPs for 16h, magCSs were cultured up to 3 days in α-MEM medium under non-magnetic or PEMF conditions. MagCSs were evaluated by immunocytochemistry, and real time RT-PCR for tendon markers. Cell metabolic activity was also assessed by MTS and ECM proteins quantified by Sirius Red/Fast Green. The MagCSs effect in ameliorating healing was assessed after implantation in window defects created in the patellar tendon of rats. PEMF was externally applied (3mT, 70Hz) 3d/week for 1h (magnetotherapy). After 4 and 8w, tendons were histologically characterized for immune-detection of tendon and inflammatory markers, and for Perls van Gieson and HE stains. Blood and detoxification organs were screened for inflammatory mediators and biodistribution of MNPs, respectively. In vitro results suggest that PEMF stimulates cellular metabolic activity, influences protein synthesis and the deposition of collagen and non-collagenous proteins is significantly increased compared to non-magnetic conditions. No adverse reactions, as infection or swelling, were observed after surgery or during follow-up. After 8w, magCSs remained at the implantation site and no MNPs were detected on detoxification organs. Plasma levels of IL1α, β, IL6 and TNFα assessed by multiplex assay were below detectable values (<12.5pg/ml). Thus, the combination of cell sheets and magnetic technologies hold promise for the development of living tendon substitutes. Acknowledgement to ERC-COG MagTendon772817, H2020 Achilles 810850, FCT - 2020.01157.CEECIND

Approximately 30% of general practice consultations for musculoskeletal pain are related to tendon disorders, causing substantial personal suffering and enormous related healthcare costs. Treatments are often prone to long rehabilitation times, incomplete functional recovery, and secondary complications following surgical repair. Overall, due to their hypocellular and hypovascular nature, the regenerative capacity of tendons is very poor and intrinsically a disorganized scar tissue with inferior biomechanical properties forms after injury. Therefore, advanced therapeutic modalities need to be developed to enable functional tissue regeneration within a degenerative environment, moving beyond pure mechanical repair and overcoming the natural biological limits of tendon healing. Our recent studies have focused on developing biologically augmented treatment strategies for tendon injuries, aiming at restoring a physiological microenvironment and boosting endogenous tissue repair. Along these lines, we have demonstrated that the local application of mesenchymal stromal cell-derived small extracellular vesicles (sEVs) has the potential to improve rotator cuff tendon repair by modulating local inflammation and reduce fibrotic scarring. In another approach, we investigated if the local delivery of the tendon ECM protein SPARC, which we previously demonstrated to be essential for tendon maturation and tissue homeostasis, has the potential to enhance tendon healing. Finally, I will present results demonstrating the utility of nanoparticle-delivered, chemically modified mRNAs (cmRNA) to improve tendon repair

Tendon injuries present a major clinical challenge, as they necessitate surgical intervention and are prone to fibrotic progression. Despite advances in physical therapy and surgical technique, tendons fail to return to full native functioning, underlining the need for a biological therapeutic to improve tendon healing. Myofibroblasts are activated fibroblasts that participate in the proliferative and remodeling phases of wound healing, and while these matrix-producing cells are essential for proper healing, they are also linked to fibrotic initiation. A subset of tenocytes has been shown to give rise to the myofibroblast fate, and potentially contribute to fibrotic tendon healing. A viable anti-fibrotic therapy in other tissues has been reprogramming the fibroblast-myofibroblast differentiation route, avoiding a more pro-fibrotic myofibroblast phenotype. Thus, defining the molecular programs that underlie both physiological and pathological tendon healing is critical for the development of potential pharmacologic treatments. Towards that end, we have taken advantage of spatial transcriptomics, using the tenocyte marker Scleraxis as a tool, and have outlined three major spatiotemporally distinct tenocyte differentiation trajectories (synthetic, proliferative, and reactive) following acute tendon injury in mouse FDL. We have further outlined key transcriptional controls that may be manipulated to alter the differentiation process and influence the resulting myofibroblast phenotype, thereby promoting regenerative tendon healing

Tendinopathy is the most frequent musculoskeletal disease that requires medical attention. Mechanical overload has been considered as a key driver of its pathology. However, the underline mechanism on how overload induces tendinopathy and inflammation is unclear. Extracellular mitochondria (EM) are newly identified as cell-to-cell communicators. The aim of this study is to elucidate the role of mitochondria in overload-induced inflammation. We performed three-dimensional uniaxial stretching to mouse tendon organoid in bioreactors. Cyclic strain of uniaxial loadings included underload, normal load, and overload, according to previous work. We then harvested microvesicles including EM, from the bioreactor by differential centrifugation and evaluated their characteristics by flow cytometry and super-resolution confocal microscopy. Raw 264.7 mouse macrophage cell line was used for chemotaxis assay in a Boyden Chamber System with Magnetic-Activated Cell Sorting Technology. EM induced cytokines secretion by macrophages was analyzed by a bead-based multiplex assay panel. N-Acetyl-L-cysteine (NAC) was used as the antioxidant to tendon organoid to regulate mitochondrial fitness. We showed mechanical load induced tendon organoid to release microvesicles including mitochondria. The size of microvesicles is mainly in the range from 220nm to 880nm. More than 75% of microvesicles could be stained by PKH26, confirming they were with lipophilic membrane. Super-resolution confocal microscopy identified two forms of mitochondria, including mitochondria encapsulated in vesicles and free mitochondria. Overload led to the degeneration of the organoid and induced microvesicles release containing most EM. Chemotaxis assay showed that EM from overloaded tendon organoid induced macrophages chemotaxis. In addition, microvesicles extracted from overloaded tendon organoid induced the production of proinflammatory cytokines including IL-6, KC (Keratinocyte-Derived Chemokine) and IL-18. NAC treatment to tendon cells could attenuate overload-induced macrophage chemotaxis. Overload induces EM releasing from tendon cells, which leads to chemotaxis of macrophages toward tendon, resulting in induction of inflammation

Aims. Posterior malleolar (PM) fractures are commonly associated with ankle fractures, pilon fractures, and to a lesser extent tibial shaft fractures. The tibialis posterior (TP) tendon entrapment is a rare complication associated with PM fractures. If undiagnosed, TP entrapment is associated with complications, ranging from reduced range of ankle movement to instability and pes planus deformities, which require further surgeries including radical treatments such as arthrodesis. Methods. The inclusion criteria applied in PubMed, Scopus, and Medline database searches were: all adult studies published between 2012 and 2022; and studies written in English. Outcome of TP entrapment in patients with ankle injuries was assessed by two reviewers independently. Results. Four retrospective studies and eight case reports were accepted in this systematic review. Collectively there were 489 Pilon fractures, 77 of which presented with TP entrapment (15.75%). There were 28 trimalleolar fractures, 12 of which presented with TP entrapment (42.86%). All the case report studies reported inability to reduce the fractures at initial presentation. The diagnosis of TP entrapment was made in the early period in two (25%) cases, and delayed diagnosis in six (75%) cases reported. Using modified Clavien-Dindo complication classification, 60 (67%) of the injuries reported grade IIIa complications and 29 (33%) grade IIIb complications. Conclusion. TP tendon was the commonest tendon injury associated with pilon fracture and, to a lesser extent, trimalleolar ankle fracture. Early identification using a clinical suspicion and CT imaging could lead to early management of TP entrapment in these injuries, which could lead to better patient outcomes and reduced morbidity. Cite this article: Bone Jt Open 2024;5(3):252–259

Recent studies on animal models focused on the effect of preserving tendon remnant of rotator cuff on tendon healing. A positive effect by combining tendon remnant preservation and small bone vents on the greater tuberosity in comparison with standard tendon-to-bone repair has been shown. The purpose of the present clinical study was to evaluate the efficacy of biologic augmentation of arthroscopic rotator cuff repair by maintaining tendon remnant on rotator cuff footprint combined with small bone vents of the greater tuberosity. A retrospective study was conducted. All patients who underwent arthroscopic rotator cuff repair associated with small bone vents (nanofractures) and tendon footprint preservation were considered eligible for the study. Inclusion criteria were: diagnosis of full-thickness rotator cuff tear as diagnosed at preoperative magnetic resonance imaging (MRI) and confirmed at the time of surgery; minimum 24-month of follow-up and availability of post-operative MRI performed not earlier than 6 months after surgery. Exclusion criteria were: partial thickness tears, irreparable tears, capsulo-labral pathologies, calcific tendonitis, gleno-humeral osteoarthritis and/or previous surgery. Primary outcome was the ASES score. Secondary outcomes were: Quick-DASH and WORC scores, and structural integrity of repaired tendons by magnetic resonance imaging (MRI) performed six months after surgery. A paired t-test was used to compare pre- and postoperative clinical outcomes. Subgroup analysis was performed according to tear size. Significance was set at p < 0.05. The study included 29 patients (M:F = 15:14). Mean age (+ SD) of patients was 61.7 + 8.9 years. Mean follow-up was 27.4 ± 2.3 months. Comparison between pre- and postoperative functional scores showed significant clinical improvement (p < 0.001). Subgroup analysis for tear size showed significant differences in the QuickDASH score (0.04). Particularly, a significant difference in the QuickDASH score could be detected between medium and large tears (p=0.008) as well as medium and massive lesions (p=0.04). No differences could be detected between large and massive tears (p= 0.35). Postoperative imaging showed healed tendons in 21 out of 29 (72%) cases. Preservation of tendon remnant combined with small bone vents in the repair of medium-to-massive full-thickness rotator cuff tears provided significant improvement in clinical outcome compared to baseline conditions with complete structural integrity in 72% of the cases

Adipose-derived stem cells (ADSCs) are an effective alternative for Teno-regeneration. Despite their applications in tendon engineering, the mechanisms promoting tendon healing still need to be understood. Since there is scattered information on ovine ADSCs, this research aims to investigate in vitro their teno-differentiation for potential use in preclinical tendon regeneration models. Ovine ADSCs were isolated from the tail region according to FAT-STEM laboratories, expanded until passage six (P6), and characterized in terms of stemness, adhesion and MHC markers by Flow Cytometry (FCM) and immunocytochemistry (ICC). Cell proliferation and senescence were evaluated with MTT and Beta-galactosidase assays, respectively. P1 ADSCs’ teno-differentiation was assessed by culturing them with teno-inductive Conditioned Media (CM) or engineering them on tendon-mimetic PLGA scaffolds. ADSCs teno-differentiation was evaluated by morphological, molecular (qRT-PCR), and biochemical (WesternBlot) approaches. ADSCs exhibited mesenchymal phenotype, positive for stemness (SOX2, NANOG, OCT4), adhesion (CD29, CD44, CD90, CD166) and MHC-I markers, while negative for hematopoietic (CD31, CD45) and MHC-II markers, showing no difference between passages. ICC staining confirmed these results, where ADSCs showed nuclear positivity for SOX2 (≅ 56%) and NANOG (≅ 67%), with high proliferation capacity without senescence until P6. Interestingly, ADSCs cultured with the teno-inductive CM did not express tenomodulin (TNMD) protein or gene. Conversely, ADSCs seeded on scaffolds teno-differentiated, acquiring a spindle shape supported by TNMD protein expression at 48h (p<0.05 vs. ADSCs 48h) with a significant increase at 14 days of culture (p<0.05 vs. ADSCs + fleece 48h). Ovine ADSCs respond differently upon distinct teno-inductive strategies. While the molecules on the CM could not trigger a teno-differentiation in the cells, the scaffold's topological stimulus did, resulting in the best strategy to apply. More insights are requested to better understand ovine ADSCs’ tenogenic commitment before using them in vivo for tendon regeneration. Acknowledgements: This research is part of the P4FIT project ESR5, under the H2020MSCA-ITN-EJD-P4 FIT-Grant Agreement ID:955685

Tendon injury is debilitating and recalcitrant. With limited knowledge of disease aitiology we have are lacking in effective treatments for this prevalent musculoskeletal complaint. This presentation will outline our findings over the past few years in which we have demonstrated the importance of the interfascicular matrix (IFM) niche in maintaining healthy tendon function and driving disease progression. 1,2. It will also continue to describe our progress in developing both in vivo and in vitro models to interrogate disease progression. We have developed and validated a rat Achilles tendon overload model, in order to explore the impact of loading on IFM and fascicle structure, and the resulting cell response. Data highlights that structural disruption and inflammatory response both initiate in the IFM region, and can be seen in the absence of demonstrable changes to animal gait, indicating a sub-injury response in the tendon which we hypothesis may drive increased matrix turnover and repair. 3. . We are now looking to interrogate the pathways driving this inflammatory behaviour in an organ-chip model, exploring the interplay between IFM cells and cells within fascicles. We have demonstrated phenotypic distinction of cells from the two niche environments, localized the progenitor phenotype to the IFM region and demonstrated significant mechanosensitivity in the IFM cell population. 4. We are currently building appropriate niche environments to maintain cell phenotype in our in vitro models, to explore the metabolic changes associated with disease progression. Acknowledgements: This body of work has received funding from: BBSRC (BB/K008412 /1); Versus Arthritis (project grant 20262); Horserace Betting Levy Board (T5); Dunhill Medical Charity (project grant RPGF1802\23); MRC (MR/T015462/1)

Abstract. Introduction. Recurrent groin pain following periacetabular osteotomy (PAO) is a challenging problem. The purpose of our study was to evaluate the position and dynamics of the psoas tendon as a potential cause for recurrent groin pain following PAO. Methods. Patients with recurrent groin pain following PAO were identified from a single surgeon series. A total of 13 patients with 18 hips (4.7%) out of a 386 PAO, had recurrent groin pain. Muscle path of the psoas tendon was accurately represented using 3D models from CT data were created with Mimics software. A validated discrete element model using rigid body springs was used to predict psoas tendon movement during hip circumduction and walking. Results. Five out of the 18 hips did not show any malformations at the osteotomy site. Thirteen hips (72%) showed malformation secondary to callus at the superior pubic ramus. These were classified into: osteophytes at the osteotomy site, hypertrophic callus or non-union and malunion at the osteotomy. Mean minimal distance of the psoas tendon to osteophytes was found to be 6.24 mm (n=6) and to the osteotomy site was 14.18 mm (n=18). Conclusions. Recurrent groin pain after PAO needs a thorough assessment. One need to have a high suspicion of psoas issues as a cause. 3D CT scan may be necessary to identify causes related to healing of the pubic osteotomy. Dynamic ultrasound of the psoas psoas tendon may help in evaluating for psoas impingement as a cause of recurrent groin pain in these cases

An isolated avulsion fracture of the peroneus longus tendon is seldom seen and potentially can go undiagnosed using basic imaging methods during an initial emergency visit. If not managed appropriately it can lead to chronic pain, a reduced range of motions and eventually affect mobility. This article brings to light the effectiveness of managing such injuries conservatively. A 55 year old postman presented to clinic with pain over the instep of his right foot for 2 months with no history of trauma. Clinically the pain was confined to the right first metatarsophalangeal joint with occasional radiation to the calf. X-ray films did not detect any obvious bony injury. MR imaging revealed an ununited avulsion fracture of the base of the 1st metatarsal. The patient was subsequently injected with a mix of steroid and local anesthetic injections at the painful nonunion site under fluoroscopic guidance. Post procedure there was no neurovascular deficit. The patient was reviewed at three months and his pain score and functional outcome improved significantly. Moreover following our intervention, the Manchester Oxford Foot Questionnaire reduced from 33 to 0. At the one year follow up he remained asymptomatic and was discharged. The peroneus longus tendon plays a role in eversion and planter flexion of foot along with providing stabilization to arches of foot. The pattern of injury to this tendon is based on two factors one is the mechanism of insult, if injured, and second is the variation in the insertion pattern of peroneus longus tendon itself. There is no gold standard treatments by which these injuries can be managed. If conservative management fails we must also consider surgery which involves percutaneous fixation, or excision of the non-healed fracture fragment and arthrodesis. To conclude isolated avulsion fractures of peroneus longus tendon are rare injuries and it is important to raise awareness of this injury and the diagnostic and management challenges faced. In this case conservative management was a success in treating this injury however it is important to take factors such as patient selection, patient autonomy and clinical judgement into account before making the final decision

Digital Ventilated Cages (DVC) offer an innovative technology to obtain accurate movement data from a single mouse over time [1]. Thus, they could be used to determine the occurrence of a tendon damage event as well as inform on tissue regeneration [2,3]. Therefore, using the mouse model of tendon experimental damage, in this study it has been tested whether the recovery of tissue microarchitecture and of extracellular matrix (ECM) correlates with the motion data collected through this technology. Mice models were used to induce acute injury in Achilles tendons (ATs), while healthy ones were used as control. During the healing process, the mice were housed in DVC cages (Tecniplast) to monitor animal welfare and to study biomechanics assessing movement activity, an indicator of the recovery of tendon tissue functionality. After 28 days, the AT were harvested and assessed for their histological and immunohistochemical properties to obtain a total histological score (TSH) that was then correlated to the movement data. DVC cages showed the capacity to distinguish activity patterns in groups from the two different conditions. The data collected showed that the mice with access to the mouse wheel had a higher activity as compared to the blocked wheel group, which suggests that the extra movement during tendon healing improved motion ability. The histological results showed a clear difference between different analyzed groups. The bilateral free wheel group showed the best histological recovery, offering the highest TSH score, thus confirming the results of the DVC cages and the correlation between movement activity and structural recovery. Data obtained showed a correlation between TSH and the DVC cages, displaying structural and movement differences between the tested groups. This successful correlation allows the usage of DVC type cages as a non-invasive method to predict tissue regeneration and recovery. Acknowledgements: This research is part of the P4FIT project ESR13, funded by the H2020-ITN-EJD MSCA grant agreement No.955685

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration

Extensor mechanism and abductor reconstructions in total joint arthroplasty are problematic. Growing tendon into a metallic implant would have great reconstructive advantages. With the introduction of porous metal implants, it was hoped that tendons could be directly attached to implants. However, the effects of the porous metal structure on tissue growth and pore penetration is unknown. In this rat model, we investigated the effect of pore size on tendon repair fixation using printed titanium implants with differing pore sizes. There were four groups of six Sprague Dawley rats (n = 28) plus control (n=4). Implants had pore sizes of 400µm (n=8), 700µm (n=8), and 1000µm (n=8). An Achilles tendon defect was created, and the implant positioned and sutured between the cut ends. Harvest occurred at 12-weeks. Half the specimens underwent tensile load to failure testing, the other half fixed and processed for hard tissue analysis. Average load to failure was 72.6N for controls (SD 10.04), 29.95N for 400µm (SD 17.95), 55.08N for 700µm (SD 13.47), and 63.08N for 1000µm (SD 1.87). The load to failure was generally better in the larger pore sizes. Histological evaluation showed that there was fibrous tendon tissue within and around the implant material, with collagen fibers organized in bundles. This increases as the pore diameter increases. Printing titanium implants allows for precise determination of pore size and structure. Our results showed that tendon repair utilizing implants with 700µm and 1000µm pores exhibited similar load to failure as controls. Using a defined pore structure at the attachment points of tendons to implants may allow predictable tendon to implant reconstruction at the time of revision arthroplasty

Partial thickness abductor tendon tears are a significant source of recalcitrant laterally based hip pain. For those that fail conservative treatment, the results of endoscopic repair are highly successful with minimal morbidity. The principal burden is the protracted rehabilitation that is necessary as part of the recovery process. There is a wide gap between failed conservative treatment and successful surgical repair. It is hypothesized that a non-repair surgical strategy, such as a bioinducitve patch, could significantly reduce the burden associated recovery from a formal repair. Thus, the purpose of this study is to report the preliminary results of this treatment strategy. Symptomatic partial thickness abductor tendon tears are treated conservatively, including activity modification, supervised physical therapy and ultrasound guided corticosteroid injections. Beginning in January 2022, patients undergoing hip arthroscopy for intraarticular pathology who also had persistently symptomatic partial thickness abductor tendon tears, were treated with adjunct placement of a bioinducitve (Regeneten) patch over the tendon lesion from the peritrochanteric space. The postop rehab protocol is dictated by the intraarticular procedure performed. All patients are prospectively assessed with a modified Harris Hip Score (mHHS) and iHOT and the tendon healing response examined by ultrasound. Early outcomes will be presented on nine consecutive cases. Conclusions - Will be summarized based on the preliminary outcomes to be reported

Introduction and Objective. In the elderly population, chronic rotator cuff tears are often associated with high re-rupture rates after surgical tendon refixation. Implant materials, especially in combination with additives are supposed to positively influence healing outcome. Furthermore, adequate mechanical properties are crucial. In order to realize degradable implants with high specific surface area, polycaprolactone (PCL) was chosen as basic material and processed by electrospinning to achieve a high surface area for growth factor implementation and subsequent cell attachment. Materials and Methods. PCL (M. n. approx. 80,000 g/mol) was used to generate fibre mats by electrospinning (relative collector velocity 8 m/s; flow rate of 4 ml/h). Mechanical analysis was performed according to EN ISO 527–2:2012 with test specimen 1BA (5 mm in diameter). Maximum force at failure (Fmax) as well as stiffness were evaluated. For preclinical in vivo testing, a coating with CS-g-PCL was performed to increase cellular adhesion and biological integration. Native and TGF-ß3 loaded mats were examined in a chronic rat tendon defect model with dissection of the M. infraspinatus, four week latency and following refixation at the humerus with different PCL-fibre mats (approval Nr. 33.12–42502–04–15/2015). After 8 weeks, rats were finalized and tendon-bone insertions were analyzed biomechanically and via histological methods. Results. Electrospun PCL-fibre mats (n = 6) showed maximum forces of 2.19 ± 0.8 N and a stiffness of 0.38 ± 0.12 N/mm. Native rat infraspinatus tendons showed Fmax values of 28.4 ± 7.2 N and a stiffness of 11.8 ± 4.9 N/mm. After implantation, Fmax of the implant-tendon-regenerate was significantly lower in CS-g-PCL - fibre mat groups compared to native control tendons (mean 52 % of native tendon value). Functionalization with TGF-ß3 led to increased Fmax (78 % of the native tendon value). However, differences were not statistically significant. Histological evaluation revealed no differences between non loaded and TGF-ß3 loaded mats. The implants were strongly disintegrated. Granulation tissue and a high number of foreign body giant cells were present. Conclusions. Although mechanical properties of fabricated mats were low, loading of the fibre mats influenced the biomechanical outcome of refixed tendons, presumably due to their high potential for binding biological active substances like TGF-ß3. However, in ongoing studies these cell reactions, especially regarding polarization of macrophages and foreign body cells need to be characterized. This research project has been supported by the German Research Foundation “Graded Implants FOR 2180 – tendon- and bone junctions” WE 4262/6-2 and parts were published in J Tissue Eng Regen Med. 2020 Jan;14(1):186–197. doi: 10.1002/term.2985

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon. Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1β than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1β was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-β1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1β had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process

The exact pathways of collagen remodeling in tendon tissue are not well understood. Therefore, we have established an ex vivo 3D collagen gel-based system and we studied the remodeling capacity of two different TSPC lines from young, Y-TSPC and aged/degenerative, A-TSPC donors. Here, we specifically focused on investigating the involvement of integrin receptors in the remodeling process. Integrins are transmembrane receptors consisting of alpha (a) and beta (b) subunits, which form cell-to-matrix bonds, activate various pathways and thereby control cell proliferation, differentiation and survival. Y- and A-TSPC were derived from human Achilles tendons and are fully described in Kohler et al. 2013. RT-PCR was used to assess the expression of collagen-binding integrins in the TSPC cultivated in collagen gels. Next, a1 and a11 integrins were silenced by stable lentiviral delivery of target-specific shRNA in the Y-TSPC. Control (con-shRNA), integrin (a1-shRNA) and integrin a11 (a11-shRNA) virus-containing supernatant was given for 24h and then cells were selected with 50 microg./ml zeocin for 10 days. The integrin knockdown (KD) efficiency was assessed by quantitative PCR and western blotting. Last, functional tests were carried out by time-lapse recording gel contraction of four cell groups (Y-TSPC+con, Y-TSPC+a1KD, Y-TSPC+a11KD, and A-TSPC). Among the screened integrins we found that integrin a1 and a11 were significantly downregulated in A-TSPC with 3.8 and 5.6 folds, correspondingly. Therefore, to mimic the A-TSPC we carried out a gene KD of a1 and a11 in Y-TSPC. PCR and western blot clearly validated the efficient KD. Analyses of collagen contraction, revealed that Y-TSPC+a11KD significantly reduced collagen contractability comparable to A-TSPC. This indicated the indispensable role of this integrin in the signaling pathway of collagen matrix remodeling. In respect to integrin a1, we found that this receptor did not affect the contraction rate of Y-TSPC, which was similar to Y-TSPC+con. To our knowledge we have now identified for the first time the critical role of a11 integrin receptor in tendon collagen remodeling, and a follow up analysis of its exact downstream cascade is on the way. Future efforts in deciphering how tendon matrix makeover is regulated can lead to innovation in preventive strategies for tendon degeneration

Summary:. Hamstring tendons (HT) represent a widely used autograft for ACL reconstruction. Harvesting, processing and pretensioning procedures together with the time out of the joint could theoretically hamper tendon cells (TCs) viability. The authors hypothesize that HT cells are not impaired at the end of the surgical procedures and their tenogenic phenotype may be strongly improved by exposure to PEMF. Methods. Remnants of semitendinosus and gracilis tendons were collected at the end of the surgical procedures before skin closure from 15 healthy donors who underwent ACL reconstruction with autologous hamstring tendons. To isolate TCs, the tendon was minced and digested with 0.3 % type I collagenase and the nucleated cells were plated at a density 5x10E3 cells/cm2 and cultured in chamber slides in differentiation medium composed of DMEM + 5ng/ml basic fibroblast growth factor (b-FGF) for 7, 14, 21 days. The following cell cultures were set up:. -. TCs cultured with differentiation medium + exposure to PEMF 8 h/day (PEMF generator system IGEA, intensity of magnetic field = 1.5 mT, frequency = 75 Hz). -. TCs cultured with differentiation medium without exposure to PEMF. At day 0, day 7, day 14 and day 21, immunofluorescence analysis was performed to evaluate the expression of collagen type I, collagen type VI, scleraxis and PCNA (proliferative marker). Subsequently, tendon explant cultures were set up to verify, at day 21, explant viability and the expression of collagen type I, collagen type VI, beta-catenin and PCNA. Results. The TCs from the tendon fragments at the end of the ACL reconstruction were alive and they expressed markers of proliferation and tendon phenotype at the end of the culture periods. The TCs in the presence PEMF 8h/day showed greater production of collagen type I, collagen type VI and scleraxis than that of TCs cultured without PEMF (p<0,05): the expression of this markers increased from 7 to 21 days of culture. The expression of PCNA, in the presence of PEMF stimulus, was significantly lower (p<0,05) than that of TCs cultured without PEMF. A similar behavior was surprisingly observed in tendon explant cultures. Conclusions. Hamstring tendons used for ACL reconstruction are not simple autologous tenoconductive scaffold but are a biologic structure rich in progenitor cells that show tenogenic behavior. Their tenogenic phenotype may be strongly improved by exposure to PEMF. In a future clinical perspective, the postoperative use of PEMF could be used to enhance the ligamentization processes of autologous hamstring tendons, when used as autografts for ACL reconstructions

Aims. To systematically review the efficacy of split tendon transfer surgery on gait-related outcomes for children and adolescents with cerebral palsy (CP) and spastic equinovarus foot deformity. Methods. Five databases (CENTRAL, CINAHL, PubMed, Embase, Web of Science) were systematically screened for studies investigating split tibialis anterior or split tibialis posterior tendon transfer for spastic equinovarus foot deformity, with gait-related outcomes (published pre-September 2022). Study quality and evidence were assessed using the Methodological Index for Non-Randomized Studies, the Risk of Bias In Non-Randomized Studies of Interventions, and the Grading of Recommendations Assessment, Development and Evaluation. Results. Overall, 17 studies (566 feet) were included: 13 studies used clinical grading criteria to report a postoperative ‘success’ of 87% (75% to 100%), 14 reported on orthotic use with 88% reduced postoperative use, and one study reported on ankle kinematics improvements. Ten studies reported post-surgical complications at a rate of 11/390 feet (2.8%), but 84 feet (14.8%) had recurrent varus (68 feet, 12%) or occurrence of valgus (16 feet, 2.8%). Only one study included a patient-reported outcome measure (pain). Conclusion. Split tendon transfers are an effective treatment for children and youth with CP and spastic equinovarus foot deformities. Clinical data presented can be used for future study designs; a more standardized functional and patient-focused approach to evaluating outcomes of surgical intervention of gait may be warranted. Cite this article: Bone Jt Open 2023;4(5):283–298

Poor tendon repair is an unsolved issue in clinical practice, due to complex tendon structure. Tendon stem/progenitor cells (TSPCs) play key roles in homeostasis, regeneration, and inflammation regulation in acute tendon injuries, and rely on TGF-β signaling for recruitment into degenerative tendons. In this study, we aimed to develop an in vitro model for tenogenesis adopting a dynamic culture of a fibrin 3D scaffold, bioengineered with human TSPCs collected from both healthy and tendinopathic surgery explants (Review Board prot./SCCE n.151, 29 October 2020). 3D culture was maintained for 21 days under perfusion provided by a custom-made bioreactor, in a medium supplemented with hTGF-β1 at 20 ng/mL. The data collected suggested that the 3D in vitro model well supported survival of both pathological and healthy cells, and that hTGF-β signaling, coupled to a dynamic environment, promoted differentiation events. However, pathological hTSPCs showed a different expression pattern of tendon-related genes throughout the culture and an impaired balance of pro-inflammatory and anti-inflammatory cytokines, compared to healthy hTSPCs, as indicated by qRT-PCT and immunofluorescence analyses. Additionally, the expression of both tenogenic and cytokine genes in hTSPCs was influenced by hTGF-β1, indicating that the environment assembled was suitable for studying tendon stem cells differentiation. The study offers insights into the use of 3D cultures of hTSPCs as an in vitro model for investigating their behavior during tenogenic events and opens perspectives for following the potential impact on resident stem cells during regeneration and healing events

Vascular inflammation and activation of myofibroblasts are significant contributors to the progression of fibrosis, which can severely impair tissue function. In various tissues, including tendons, Transforming growth factor beta 1 (TGF-β1) has been identified as a critical driver of adhesion and scar formation. Nevertheless, the mechanisms that underlie fibrotic peritendinous adhesions are still not well comprehended, and human microphysiological systems to help identify effective therapies remain scarce. To address this issue, we developed a novel human Tendon-on-a-Chip (hToC), comprised of an endothelialized vascular compartment harboring circulating monocytes and separated by a 5 μm/100 nm dual-scale ultrathin porous membrane from a type I/III collagen hydrogel with primary tendon fibroblasts and tissue-resident macrophages, all under defined serum-free conditions. The hToC models the crosstalk of the various cells in the system leading to the induction of inflammatory and fibrotic pathways including the activation of mTOR signaling. Consistent with phenotypes observed in vivo in mouse models and clinical human samples, we observed myofibroblast differentiation and senescence, tissue contraction, excessive extracellular matrix deposition, and monocytes’ transmigration and macrophages’ secretion of inflammatory cytokines, which were dependent on the presence of the endothelial barrier. This model offers novel insights on the role of vasculature in the pathophysiology of adhesions, which were previously underappreciated. Moreover, in testing whether the hToC could be used to evaluate efficacy of therapeutics, we were able to capture donor-specific variability in the response to Rapamycin treatment, which reduced myofibroblast activation regardless. Thus, our findings demonstrate the value of the hToC as a human microphysiological system for investigating the pathophysiology of fibrotic conditions in the context of peritendinous injury and similar fibrotic conditions, providing an alternative to animal testing

Inability to actively supinate the forearm makes common activities of daily living and certain vocational activities awkward or impossible to perform. A total of 11 patients with deficient supination of the arm underwent transfer of the tendon of flexor carpi ulnaris to the split tendon of brachioradialis with its bony insertion into the radial styloid left intact. Active supination beyond neutral rotation was a mean of 37.2° (25° to 49.5°) at a minimum follow-up of three years, representing a significant improvement (95% confidence interval 25 to 50, p < 0.001). Functional evaluation of the hand after this transfer showed excellent and good results in ten patients and fair in one. The split tendon of brachioradialis as an insertion for transfer of the flexor carpi ulnaris appears to provide adequate supination of the forearm without altering the available pronation and avoids the domination of wrist extension sometimes associated with transfers of the flexor carpi ulnaris to the radial extensors of the wrist

Treatment of a partial laceration in zone two of a flexor tendon remains controversial. The intact part of the tendon can sustain forces of normal un-resisted motion, and repaired partially treated tendons can actually be weaker than un-repaired ones. Trimming these lacerations has been shown to be beneficial in partially lacerated tendons with triggering or entrapment. The purpose of this study is to observe the behaviour of a partially lacerated and subsequently trimmed tendon under strain, and measure their friction coefficient at different flexion angle and load. Ten long flexor tendons from long digit of turkey foot, along with the equivalent of A2 pulley were used. All experiments were carried out for intact, lacerated (50%) and trimmed tendon at 10, 30, 50 and 70 degrees of flexion and two load settings of 200 and 400g. The friction forces were measured by the difference between the two load transducers and the friction coefficient was measured using this formula, μ = Ln[(F2/F1)]/Ø. Friction coefficient (μ), Tension forces (F2 and F1), arc of tendon and pulley contact (Ø). Results: Friction coefficient increased significantly by three folds (0.3) after laceration compare with intact tendon (0.12) at both loads. This was reduced significantly after trimming the tendon but the friction coefficient was still approximately twice the value of the intact tendon (0.2). Triggering was noticed in all tendon lacerations. Triggering was reduced after trimming in 10 and 30 degrees of flexion but increased markedly at 50 and 70 degrees of flexion associated with tendon fragmentation at the trimmed area. Trimming partially lacerated flexor tendons will reduce the gliding resistance of the tendon through the pulley but this can lead to further fragmentation and triggering at higher flexion degrees and loads

Hamstring grafts have been associated with reduced strength, donor site pain and muscle strains following Anterior Cruciate Ligament Reconstruction (ACLR). Traditional graft fixation methods required both semitendinosus and gracilis tendons to achieve a graft of sufficient length and diameter, but newer techniques allow for shorter, broad single tendon grafts. This study seeks to compare the outcomes between Single Tendon (ST) and Dual Tendon (DT) ACLR, given there is no prospective randomised controlled trial (RCT) in the literature comparing outcomes between these options. In this ongoing RCT: (ANZ Clinical Trials Registry ACTRN126200000927921) patients were recruited and randomised into either ST or DT groups. All anaesthetic and surgical techniques were uniform aside from graft technique and tibial fixation. 13 patients were excluded at surgery as their ST graft did not achieve a minimum 8mm diameter. 70 patients (34 ST, 36DT) have been assessed at 6 months, using PROMS including IKDC2000, Lysholm and Modified Cincinnati Knee, visual analog scale for pain frequency (VAS-F) and severity (VAS-S), dedicated donor site morbidity score, KT-1000 assessment, and isokinetic strength. Graft diameters were significantly lesser in the ST group compared to the DT group (8.44mm/9.11mm mean difference [MD],-0.67mm; P<0.001). There was a significant and moderate effect in lower donor site morbidity in the ST group compared to the DT group (effect size [ES], 0.649; P = .01). No differences between groups were observed for knee laxity in the ACLR limb (P=0.362) or any of the patient-reported outcome measures (P>0.05). Between-group differences were observed for hamstrings strength LSI favouring the ST group, though these were small-to-moderate and non-significant (ES, 0.351; P = .147). ST (versus DT) harvest results in significantly less donor site morbidity and this is the first prospective RCT to determine this. There were no differences between ST and DT hamstring ACLR were observed in PROMs, knee laxity and hamstring strength. Younger female patients tend to have inadequate single tendon size to produce a graft of sufficient diameter, and alternative techniques should be considered. Further endpoints include radiological analysis, longer term donor site morbidity, revision rates and return to sport and will continue to be presented in the future

Introduction. Anterior cruciate ligament (ACL) injuries represent a significant burden of disease to the orthopaedic surgeon and often necessitate surgical reconstruction in the presence of instability. The hamstring graft has traditionally been used to reconstruct the ACL but the quadriceps tendon (QT) graft has gained popularity due to its relatively low donor site morbidity. Methods. This is a single centre comparative retrospective analysis of prospectively collected data of patients who had an ACL reconstruction (either with single tendon quadrupled hamstring graft or soft tissue quadriceps tendon graft). All surgeries were performed by a single surgeon using the All-inside technique. For this study, there were 20 patients in each group. All patients received the same post-operative rehabilitation protocol and were added to the National Ligament Registry to monitor their patient related outcome scores (PROM). Results. The average age of patients in the QT group was 29 years (16 males, 4 females) and in the hamstring group was 28 years (18 males, 2 females). The most common mechanism of injury in both groups was a contact twisting injury. There were no statistical differences between the two patient groups in regards to PROMS and need for further revision surgery as analysed on the National Ligament Registry. Conclusions. The all soft tissue QT graft seems to be equivocal to quadrupled hamstring graft in terms of patient function and recovery graft characteristics. Further research may be needed to elucidate the long-term results of the all soft tissue QT graft given its recent increase in use