Obese patients show a higher incidence of tendon-related pathologies. These patients present a low inflammatory systemic environment and a higher mechanical demand which can affect the tendons. In addition, inflammation might have a role in the progression of the disease as well as in the healing process. A systematic review was performed by searching PubMed, Embase and Cochrane Library databases. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results. Evaluated data were extracted and critically analysed. PRISMA guidelines were applied, and risk of bias was assessed, as well as the methodological quality of the included studies. We excluded all the articles with high risk of bias and/or low quality after the assessment. Due to the high heterogeneity present among the studies, a metanalysis could not be done. Thus, a descriptive analysis was performed. After applying the previously described criteria, thirty articles were included, assessed as medium or high quality. We analysed the data of 50865 subjects, 6096 of which were obese (BMI over 30 accordingly to the WHO criteria). The overall risk of re-tear after surgery is about the 10% more than normal BMI subjects. The rupture risk fluctuates in the studies without showing a significant trend. Obese subjects have a higher risk to develop tendinopathy and a worse outcome after surgery as confirmed in several human studies. The obesity influence on tendon structure and mechanical properties may rely on the fat tissue endocrine proprieties and on hormonal imbalance. Clinicians should consider obesity as a predisposing factor for the development of tendinopathies and for a higher risk of complications in patients who underwent surgical repair of tendons

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

Though retear rates following rotator cuff repair are well established, we set out to review current literature to determine when early retears occurred (defined as <12m following surgery), and examine which pre- and post-operative variables might affect outcome. Pubmed, Medline, and CINAHL were searched for literature published from 2011 to 2021 using specific search terms. The inclusion criteria were studies reporting retear rates within 12 months of initial surgical repair. Exclusionary criteria were studies that included partial thickness tears, and studies that did not use imaging modalities within 12 months to assess for retears. PRISMA guidelines were followed, identifying a total of 10 papers. A combined total of 3372 shoulders included (Mean age 56 −67 years). The most common modality used to identify early retears were ultrasound scan and MRI. 6 of the 10 studies completed imaging at 0-3 months, 6 studies imaged at 3-6 months and 6 studies imaged at 6-12 months. Across all studies, there was a 17% early retear rate (574 patients). Of these, 13% occurred by 3 months, whilst the peak for retears occurred at 3-6 months (82%) and 5% occurred at 6-12 months. The risk of retear was higher in larger tears and extensive tendon degeneration. All studies apart from one documented a return to work/sport at 6 months post-operatively. Postoperative rehabilitation does not appear to alter retear rate, although data is limited with only 1 of 10 studies allowing active range of movement before 6 weeks. Retorn tendons had poorer functional outcomes compared to intact tendons at 12m following initial repair. The majority of early retears occur at 3-6 months and this time period should be prioritised both in rehabilitation protocols and future research. Age, tear size, and tendon degeneration were found to influence likelihood of early retears

Introduction. Supraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells. Method. Porcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05. Result. One day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05). Conclusion. Human tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing exploration of the distinctive effect of different motions on tendon regeneration towards engineering tissue grafts. This work was supported by the Engineering and Physical Sciences Research Council EP/S003509/1

Obesity is associated with poor outcomes and increased risk of failure after rotator cuff (RC) repair surgery. The effect of diet-induced obesity (DIO) on enthesis healing has not been well characterised and whether its effects can be reversed with dietary intervention is unknown. We hypothesised that DIO would result in inferior enthesis healing in a rat model of RC repair and that dietary intervention in the peri-operative period would improve enthesis healing. A total of 78 male Sprague-Dawley rats were divided into three weight-matched groups from weaning and fed either: control diet (CD), high-fat diet (HFD), or HFD until surgery, then CD thereafter (HF-CD). After 12 weeks the left supraspinatus tendon was detached, followed by immediate surgical repair. At 2 and 12 weeks post-surgery, animals were cullers and RCs harvested for biomechanical and histological evaluation. Body composition and metabolic markers were assessed via DEXA and plasma analyses, respectively. DIO was established in the HFD and HF-CD groups prior to surgery, and subsequently reversed in the HF-CD group after surgery. At 12 weeks post-surgery, plasma leptin concentrations were higher in the HFD group compared to the CD group (5.28 vs. 2.91ng/ml, P=0.003). Histologically, the appearance of the repaired entheses was poorer in both the HFD and HF-CD compared to the CD group at 12 weeks (overall histological score 6.20 (P=0.008), 4.98 (P=0.001) and 8.68 out of 15, respectively). The repaired entheses in the HF-CD group had significantly lower (26.4 N, P=0.028) load-at-failure 12 weeks post-surgery compared to the CD group (34.4 N); while the HFD group was low, but not significantly different (28.1 N, P=0.096). Body mass at the time of surgery, plasma leptin and body fat percentage were negatively correlated with histological scores and plasma leptin with load-at-failure 12 weeks post-surgery. DIO impaired enthesis healing in this rat RC repair model, with inferior biomechanical and histological outcomes. Restoring normal weight with dietary change after surgery did not improve healing outcomes. Exploring interventions that improve the metabolic state of obese patients and counselling patients appropriately about their modest expectations after repair should be considered

The function of the upper extremity is highly dependent on correlated motion of the shoulder. The shoulder can be affected by several diseases. The most common are: rotator cuff tear (RCT), shoulder instability, shoulder osteoarthritis and fractures. Rotator cuff disease is a common disorder. It has a high prevalence rate, causing high direct and indirect costs. The appropriate treatment for RCT is debated. The American Academy Orthopaedic Surgeons guidelines state that surgical repair is an option for patients with chronic, symptomatic full-thickness RCT, but the quality of evidence is unconvincing. Thus, the AAOS recommendations are inconclusive. We are performing a randomized controlled trial to compare surgical and conservative treatment of RCT, in term of functional outcomes, rotator cuff integrity, muscle atrophy and fatty degeneration. Shoulder instability occurs when the head of the upper arm bone is forced out of the shoulder socket. Shoulder instabilities have been classified according to the etiology, the direction of instability, or on combinations thereof. The Thomas and Matsen classification, which is currently the most commonly utilized classification, divides shoulder instability events into the traumatic, unidirectional, Bankart lesion, and surgery (TUBS) and the atraumatic, multidirectional, bilateral, rehabilitation, and capsular shift (AMBRI) categories. The acquired instability overstress surgery (AIOS) category was then added. Surgical procedures for shoulder instability includes arthroscopic capsuloplasty, remplissage, bone block procedure or Latarjet procedure. Reverse total shoulder arthroplasty (RTSA) represents a good solution for the management of patients with osteoarthritis or fracture of the proximal humerus, with associated severe osteoporosis and RC dysfunction

Introduction and Objective. The human body is designed to walk in an efficient way. As energy can be stored in elastic structures, it is no surprise that the strongest elastic structure of the human body, the iliofemoral ligament (IFL), is located in the lower limb. Numerous popular surgical hip interventions, however, affect the structural integrity of the hip capsule and there is a growing evidence that surgical repair of the capsule improves the surgical outcome. Though, the exact contribution of the iliofemoral ligament in energy efficient hip function remains unelucidated. Therefore, the objective of this study was to evaluate the influence of the IFL on energy efficient ambulation. Materials and Methods. In order to assess the potential passive contribution of the IFL to energy efficient ambulation, we simulated walking using the large public dataset (n=50) from Schreiber in a the AnyBody musculoskeletal modeling environment with and without the inclusion of the IFL. The work required from the psoas, iliacus, sartorius, quadriceps and gluteal muscles was evaluated in both situations. Considering the large uncertainty on ligament properties a parameter study was included. Results. A significant reduction in the active component of all hip flexors was observed when the IFL is intact. The required muscle work was found to be reduced by as much as 48% (CI: 29–62%), 61% (CI: 35–84%) and 38% (CI: 2–69%) for the psoas, iliacus, and sartorius muscle respectively. The IFL inclusion has no major effect on the required work from the quadriceps and the gluteal muscle group. The energy storage in the IFL is largest at maximal hip extension and the contribution to forward motion is the largest at the start of the swing phase. Conclusions. The iliofemoral ligament seems to be a crucial structure in energy efficient walking. The findings support need for meticulous reconstruction of the capsule ligament in case of surgical damage

Abstract. Objectives. Tendon and ligament injury poses an increasingly large burden to society. With surgical repair and grafting susceptible to high failure rates, tissue engineering provides novel avenues for treatment. This systematic review explores in vivo evidence whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) can facilitate tendon and ligament repair in animal models. Methods. On May 26th 2021, a systematic search was performed on PubMed, Web of Science, Cochrane Library, Embase, using search terms ‘mesenchymal stem cell’ or ‘multipotent stem cell’ AND ‘extracellular vesicles’ or ‘exosomes’ AND ‘tendon’ or ‘ligament’ or ‘connective tissue’. Risk of bias was assessed using SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) tool. Studies administering EVs isolated from human or animal-derived MSCs into in vivo models of tendon/ligament injury were included. In vitro, ex vivo, in silico studies were excluded, and studies without a control group were excluded. Data on isolation and characterisation of MSCs and EVs, and in vivo findings in animal models were extracted. Results. Out of 383 relevant studies, 11 case-control studies were included for data extraction, including a total of 448 animal subjects (range 10–90). Six studies utilised bone marrow-derived MSCs. All studies characterised their MSCs via flow cytometry, which expressed CD44 and CD90, and isolated EVs via ultracentrifugation (average diameter 125nm). Five studies utilised histological scoring systems, all of which reported a lower score with EV treatment, suggesting improved healing ability. Four studies reported increased anti-inflammatory cytokine expression (IL-10, TGF-β1); three studies reported decreased endogenous M1/M2 macrophage ratio with EV treatment. Eight studies reported increased maximum stiffness, breaking load, tensile strength in EV-treated tendons. Conclusion. MSC-EVs are effective therapeutic agents for tendon/ligament pathologies, attenuating the initial inflammatory response, and accelerating tendon matrix regeneration. Future randomised controlled trials are needed to definitely demonstrate MSC-EVs superiority in management of tendon/ligament injury

Introduction and Objective. Zone 2 flexor tendon injuries are still one of the challenges for hand surgeons. It is not always possible to achieve perfect results in hand functions after these injuries. There is no consensus in the literature regarding the treatment of zone 2 flexor tendon injuries, tendon repair and surgical technique to be applied to the A2 pulley. The narrow fibro-osseous canal structure in zone 2 can cause adhesions and loss of motion due to the increase in tendon volume due to surgical repair. Different surgical techniques have been defined to prevent this situation. In our study, in the treatment of zone 2 flexor tendon injuries; Among the surgical techniques to be performed in addition to FDP tendon repair; We aimed to compare the biomechanical results of single FDS slip repair, A2 pulley release and two different pulley plasty methods (Kapandji and V-Y pulley plasty). Materials and Methods. In our study, 12 human upper extremity cadavers preserved with modified Larssen solution (MLS) and amputated at the mid ½ level of the arm were used. A total of 36 fingers (second, third and the fourth fingers were used for each cadaver) were divided into four groups and 9 fingers were used for each group. With the finger fully flexed, the FDS and FDP tendons were cut right in the middle of the A2 pulley and repaired with the cruciate four-strand technique. The surgical techniques described above were applied to the groups. Photographs of fingers with different loads (50 – 700 gr) were taken before and after the application. Proximal interphalangeal (PIP) joint angle, PIP joint maximum flexion angle and bowstring distance were measured. The gliding coefficient was calculated by applying the PIP joint angle to the single-phase exponential association equation. Results. Gliding coefficient after repair increased by %21.46 ± 44.41, %62.71 ± 116.9, %26.8 ± 35.35 and %20.39 ± 28.78 in single FDS slip repair, A2 pulley release, V-Y pulley plasty and Kapandji plasty respectively. The gliding coefficient increased significantly in all groups after surgical applications (p<0.05). PIP joint maximum flexion angle decreased by %3.17 ± 7.92, %12.82 ± 10.94, %8.33 ± 3.29 and %7.35 ± 5.02 in single FDS slip repair, A2 pulley release, V-Y pulley plasty and Kapandji plasty respectively. PIP joint maximum flexion angle decreased significantly after surgery in all groups (p<0.05). However, there was no statistically significant difference between surgical techniques for gliding coefficient and PIP joint maximum flexion angle. Bowstring distance between single FDS slip repair, kapandji pulley plasty and V-Y pulley plasty showed no significant difference in most loads (p>0.05). Bowstring distance was significantly increased in the A2 pulley release group compared to the other three groups (p<0.05). Conclusion. Digital motion was negatively affected after flexor tendon repair. Similar results were found in terms of gliding coefficient and maximum flexion angle among different surgical methods. As single FDS slipe repair preserves the anatomical structure of the A2 pulley therefore we prefer it as an ideal method for zone 2 flexor tendon repair. However, resection of FDS slip may jeopardizes nutrition to the flexor digitorum profundus tendon which weakens the repair site. Therefore the results must be confirmed by an in vivo study before a clinical recommendation can be made. Keywords: Flexor tendon; injury; pulley plasty; cadaver;

The enthesis is a specialised zonal tissue interface between tendon and bone, essential for adequate force transmission and composed by four distinct zones, namely tendon, fibrocartilage, mineralized fibrocartilage and bone. Following injuries and surgical repair, the enthesis is often not reestablished and so far, traditionally used tissue substitutes have lacked to reproduce the complexity of the native tissue. In this work, we hypothesised that a collagen-based three-layer scaffold that mimic the composition of the enthesis, in combination with bioactive molecules, will enhance the functional regeneration of the enthesis. A three-layer sponge composed of a tendon-like layer (collagen I), a cartilage-like layer (collagen II) and a bone-like layer (collagen I and hydroxyapatite) was fabricated by an iterative layering freeze-drying technique. Scaffold porosity and structural continuity at the interfaces were assessed through SEM analysis. Bone-marrow derived stem cells (BMSCs) were seeded by syringe vacuum assisted technique on the scaffold. Scaffolds were cultured in basal media for 3 days before switching to differentiation media (chondrogenic, tenogenic and osteogenic). BMSCs metabolic activity, proliferation and viability were assessed by alamarBlue, PicoGreen and Live/Dead assays. At D21 the scaffolds were fixed, cryosectioned and Alizarin Red and Alcian Blue stainings were performed in order to evaluate BMSC differentiation towards osteogenic and chondrogenic lineage. The presence of collagen I and tenascin in the scaffolds was evaluated by immunofluorescence staining at D21 in order to assess tenogenic differentiation of BMSCs. Subsequently, the cartilage-like layer was functionalized with IGF-1, seeded with BMSCs and cultured in basal media up to D21. Structural continuity at the interfaces of the scaffolds was confirmed by SEM and scaffold porosity was assessed as >98%. The scaffolds supported cell proliferation and infiltration homogeneously throughout all the layers up to D21. Osteogenic differentiation of BMSC selectively in the bone-like layer was confirmed by Alizarin red staining in scaffolds cultured in basal and osteogenic media. Alcian blue staining revealed the presence of proteoglycans selectively in the cartilage-like layer in scaffolds cultured in chondrogenic media but not in basal media. Increased expression of the tenogenic markers collagen I and tenascin were observed in the tendon-like layer of scaffolds cultured in tenogenic but not in basal media for 21 days. The presence of IGF-1 increased osteogenic and chondrogenic differentiation of BMSCs, whereas no difference was observed for tenogenic differentiation. In conclusion, a 3-layer collagen sponge was successfully fabricated with distinct but integrated layers; the different collagen composition of the non-functionalized 3-layer sponge was able to regulate BMSC differentiation in a localized manner within the scaffold. The scaffold functionalization with IGF-1 accelerated chondrogenic and osteogenic BMSC differentiation. Overall, functionalization of the 3-layer scaffolds holds promising potential in enthesis regeneration

A rotator cuff tear is one of the most common traumatic and degenerative tendon injuries resulting in over 4.5 million physician visits in the US alone. Functional restoration of rotator cuff defects usually requires surgical repair, estimated at 300,000 cased in the US annually. However, postoperative retear of repaired tendons ranges from 20% in small to medium tears to over 90% in large and massive tears. Recently, augmentation with grafting materials to strengthen a reparable tear or to bridge an unrepairable defect has become a common and attractive strategy to reduce the retear rate, especially for large or massive tears. Current graft materials, however, have encountered great challenges in achieving these goals. To meet these challenges, we have developed an engineered tendon with layered tendon-fibrocartilage-bone composite (TFBC) from patellar-tibia unit revitalized by seeding bone marrow derived stem cells (BMDSCs) within the slices, and then reassembled to an engineered tendon. Both in vitro and in vivo results have shown that engineered TFBC enhance the biomechanical strength and biological healing using canine model

Objectives. Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Methods. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair. Results. At two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons. Conclusions. GSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred. Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J. Russell, C. L. Mendias. Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear. Bone Joint Res 2017;6:57–65. DOI: 10.1302/2046-3758.61.BJR-2016-0232.R1

Tendon injuries constitute a major healthcare burden owing to the limited healing ability of these tissues and the poor clinical outcomes of surgical repair treatments. Recent advances in tendon tissue engineering (TTE) strategies, particularly through the use of biotextile technologies, hold great promise toward the generation of artificial living tendon constructs. We have previously developed a braided construct based on suture threads coated with gelMA:alginate hydrogel encapsulating human tendon cells. These cell-laden composite fibers enabled the replication of cell and tissue-level properties simultaneously. Based on this concept, in this study we explored the use of platelet lysate (PL), a pool of supra-physiological concentrations of growth factors (GFs), to generate a hydrogel layer, which is envisioned to act as a depot of therapeutic factors to induce tenogenic differentiation of encapsulated human adipose stem cells (hASCs). For this purpose, commercially available suture threads were first embedded in a thrombin solution and then incubated in PL containing hASCs. Herein, thrombin induces the gelation of PL and consequent hydrogel formation. After coating suture threads with the mixture of PL-ASCs, cells were found to be viable and homogeneously distributed along the fibers. Strikingly, hASCs encapsulated within the PL hydrogel layer around the suture thread were able to sense chemotactic factors present in PL and to establish connections between adjacent independent fibers, suggesting a tremendous potential of PL cell-laden hydrogel fibers as building blocks in the development of living constructs aimed at tendon repair applications

Surgical repair of rotator cuff tears have high failure rates (20–70%), often due to a lack of biological healing. Augmenting repairs with extracellular matrix-based scaffolds is a common option for surgeons, although to date, no commercially available product has proven to be effective. In this study, a novel collagen scaffold was assessed for its efficacy in augmenting rotator cuff repair. The collagen scaffold was assessed in vitro for cytocompatability and retention of tenocyte phenotype using alamarBLUE assays, confocal imaging and real-time PCR. Immunogenicity was assessed in vitro by the activation of pre-macrophage cells. In vivo, using a modified rat rotator cuff defect model, supraspinatus tendon repairs were carried out in 46 animals. Overlay augmentation with the collagen scaffold was compared to unaugmented repairs. At 6- and 12-weeks post-op the repairs were tested biomechanically to evaluate repair strength, and histologically for quality of healing. The collagen scaffold supported human tenocyte growth in vitro, with cells appearing morphologically tenocytic and expressing higher tendon gene markers compared to plastic controls. No immunogenic responses were provoked compared to suture material control. In vivo, augmentation with the scaffold improved the histological scores at 12 weeks (8.37/15 vs. 6.43/15, p=0.0317). However, no significant difference was detected on mechanical testing. While the collagen scaffold improved the quality of healing of the tendon, a meaningful increase in biomechanical strength was not achieved. This is likely due to its inability to affect the bone-tendon junction. Future materials/orthobiologics must target both the repaired tendon and the regenerating bone-tendon junction

As we grow older, the risk of tendon degeneration and injuries increases, which can result in pain, disability, healthcare cost, and lost productivity. Even after surgical repair the results are often unsatisfactory. The cellular reasons for the differences in the healing potential, however, are not well studied. To get a deeper insight into the biological characteristics of tenocyte-like cells from different patient groups we established a biobank with material from over 150 human donors. The patients/donors suffered from rotator cuff tears and were operated to restore the function. A proportion of the isolated cells showed stem cell-like characteristics and was able to differentiate into the osteoblastic, chondrogenic and adipogenic linage. Investigating the differentiation potential of the cells with regard to donor characteristics, we were able to demonstrate that age, sex but also the “degeneration” has an impact of the cellular potential. A possibility to stimulate the cellular activity is the application of growth factors, as already clinically used for stimulation of bone healing. Therefore, the responsiveness of the cells to the growth factors Bone Morphogenetic protein-2/7 (BMP-2/7) was analysed in vitro. Independent of the donor characteristics, the cells responded to the BMP-stimulation by increased proliferation and collagen-1 synthesis. However, cells isolated from donors with high fatty infiltration of the muscle or older females were less responsive. Looking into the intracellular signalling pathway, the data showed that the BMP-signal is mainly mediated by the canonical-pathway with samd8 playing a major role. This basic research gives first information regarding the differences in tenocytes biology with respect to the donor and is important for the understanding of tendon regeneration and the future development of new treatment strategies

Introduction. The highest incidence of recurrent shoulder instability is in young patients, surgical repair can reduce recurrent instability and improve shoulder function. This has led to an increasing rate of stabilisation and use of MRI to identify associated injuries in first time dislocations. MRA has the benefit of distending the joint and is becoming increasingly used. The aim of this study is to establish the sensitivity and specificity of MRA in the investigation of patients with traumatic anterior shoulder dislocations. Methods. A retrospective analysis of patients undergoing both magnetic resonance arthrography and arthroscopy after a traumatic anterior shoulder dislocation between January 2011 and 2014. Images were interpreted by eight musculoskeletal radiologists and arthroscopic findings were obtained from surgical notes and used as a reference. The sensitivity, specificity and positive predictive value for the different injuries were calculated. Results. 60 patients were reviewed; 88% were male, mean age was 28 years (range 18 to 50) and 27% were primary dislocations. The overall sensitivity and specificity of MRA to all associated injuries was 0.9 (CI 0.83–0.95) and 0.94 (CI 0.9–0.96) retrospectively. The lowest sensitivity was seen in osseous Bankart 0.8 (CI 0.44–0.96) and SLAP lesions 0.5 (CI 0.14–0.86). Conclusion. MRA has a high sensitivity when used to identify associated injuries in shoulder dislocation although in 8 patients (13%) arthroscopy identified an additional injury. The overall agreement between MRA and arthroscopic findings was good but identification of GHL and rotator cuff injuries was poor. Level of Evidence. IV. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review

The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight ‘middle-aged’ baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing

Background. Re-attachment of tendon to bone is challenging with surgical repair failing in up to 90% of cases. Poor biological healing is common and characterised by the formation of weak scar tissue. Previous work has demonstrated that decellularised allogenic demineralised bone matrix (DBM) regenerates a physiologic enthesis. Xenografts offer a more cost-effective option but concerns over their immunogenicity have been raised. We hypothesised that augmentation of a healing tendon-bone interface with DBM incorporated with autologous mesenchymal stem cells (MSCs) would result in improved function, and restoration of the native enthesis, with no difference between xenogenic and allogenic scaffolds. Methods. Using an ovine model of tendon-bone retraction the patellar tendon was detached and a complete distal tendon defect measuring 1 cm was created. Suture anchors were used to reattach the shortened tendon and xenogenic DBM + MSCs (n=5) and allogenic DBM + MSCs (n=5) were used to bridge the defect. Functional recovery was assessed every 3 weeks and DBM incorporation into the tendon and its effect on enthesis regeneration was measured using histomorphometry. Results. By 12 weeks, DBM augmentation resulted in significantly improved functional weight bearing with no failures in either group. Compared to xenogenic DBM, allogenic DBM was associated with significantly higher functional weight bearing at 6 (P=0.047), 9 (P=0.028) and 12 weeks (P=0.009). This was accompanied by a more direct type of enthesis characterised by significantly more fibrocartilage and mineralised fibrocartilage. Xenograft was also associated with an immunogenic reaction despite preoperative decellularisation. Conclusion. This study shows that DBM enhances tendon-bone healing and may reduce the high failure rates associated with surgery. An immunogenic reaction, and inferior biomechanical and histological results were also associated with the use of xenograft. Allogenic DBM with autologous MSCs may be a suitable scaffold for the enhancement of tendon-bone healing in the clinical setting. Disclosures. Funded by IKC PoC grant awarded by the University of Leeds. Ethical approval. Granted by the study institution (University College London)

Background Hip fractures are one of the leading causes of hospital admissions. Surgical treatment is often associated with significant blood loss, requiring post-operative erythrocyte transfusion. Aim To assess post-operative erythrocyte transfusion rates for hip fractures and evaluate the effect of tranexamic acid (TXA). Method. All patients undergoing surgical repair of a hip fracture at RLBUHT between 1st April 2013 – 30th April 2014 were selected. Data regarding transfusion status and peri-operative TXA use was collected from electronic databases and case notes. Results. 450 patients were admitted with a hip fracture, of whom 441 underwent surgery. Modalities of hip fixation included total hip replacement (THR, n=39), hemiarthroplasty (n=145), dynamic hip screw (DHS, n=116), cannulated hip screw (CHS, n=17) and long (n=71) and short (n=53) intramedullary hip screw (IMHS). 44.2% received a post-operative erythrocyte transfusion, with an average of 2.5 units per patient (range 1–9 units). With all study subjects included, the average transfusion rates for THR, hemiarthroplasty, DHS, CHS, long IMHS and short IMHS were 0.44 units, 0.78 units, 0.97 units, 0.47 units, 1.55 units and 1.19 units respectively. Data regarding intra-operative TXA administration was available for 318 (72.1%) patients, sixty-one of whom received TXA. 27.9% given TXA required a post-operative transfusion (range 0–6 units), compared to 35.4% of patient with no intra-operative TXA (range 0–11 units), p=0.142. Conclusion. 44.2% of patients required an erythrocyte transfusion, with an average of 2.5 units per patient of those transfused. This is higher than rates quoted by other studies including Shokoohi et al who had a transfusion rate of 32.6%. Adherence to local transfusion protocols must be reviewed. There is a tendency for TXA to reduce post-operative transfusion requirements, however in this study, this did not reach statistical significance (p=0.142). A larger, randomised controlled trial is required to assess the role TXA in hip fracture surgery

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