The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations

Intra-synovial tendon injuries affect compressed tendon within a synovial environment (eg Rotator cuff tears of the shoulder) and frequently demonstrate ‘failed healing'. Current therapeutic methods for tendon tears (intra-synovial corticosteroid medication and surgical debridement) offer poor outcomes and new strategies for enhancing repair are needed. We have therefore evaluated two different approaches involving the use of mesenchymal stem cells and scaffolds. Bone marrow- and synovial-derived stem cells were capable of adhering to cut surfaces of tendon in vitro and modulating the release of extracellular matrix into the media. However, when administered in vivo into the digital flexor tendon sheath in naturally-occurring deep digital flexor tendon tears in horses and in an experimental model in sheep, neither cell type was capable of healing the tendon defect. Superparamagnetic iron oxide particle labelling of the implanted cells imaged using MRI and histologically revealed that cells only engraft into the synovium. In contrast a non-cellularised bilayered electrospun and woven polydioxanone scaffold, when used in the same experimental sheep model via a modified open approach and sutured over the created defect resulted in no local or systemic signs of excessive inflammation 3 months after implantation. All the tendon lesions healed with only a mild local inflammatory reaction and minimal-to-mild adhesion formation. Significant proliferative fibroblast infiltration was observed within and immediately adjacent to the implanted scaffold. The cellular infiltrate was accompanied by an extensive network of new blood vessel formation within the new tissue. In conclusion, the use of a scaffold to cover the defect appears to be a more successful strategy to repair intra-synovial tendon defects than intra-synovially injected mesenchymal stem cells. It remains to be tested whether the combination of the two techniques might offer an even better healing response

This study aims to compare the biomechanical properties of the “Double Lasso-Loop” suture anchor (DLSA) technique with the commonly performed interference screw (IS) technique in an ex vivo ovine model. Fourteen fresh sheep shoulder specimens were used in this study. Dissection was performed leaving only the biceps muscle attached to the humerus and proximal radius before sharply incised to simulate long head of biceps tendon (LHBT) tear. Repair of the LHBT tear was performed on all specimens using either DSLA or IS technique. Cyclical loading of 500 cycles followed by load to failure was performed on all specimens. Tendon displacement due to the cyclical loading at every 100 cycles as well as the maximum load at failure were recorded and analysed. Stiffness was also calculated from the load displacement graph during load to failure testing. No statistically significant difference in tendon displacement was observed from 200 to 500 cycles. Statistically significant higher stiffness was observed in IS when compared with DSLA (P = .005). Similarly, IS demonstrated significantly higher ultimate failure load as compared with DSLA (P = .001). Modes of failure observed for DSLA was mostly due to suture failure (7/8) and anchor pull-out (1/8) while IS resulted in mostly LHBT (4/6) or biceps (2/6) tears. DSLA failure load were compared with previous studies and similar results were noted. After cyclical loading, tendon displacement in DLSA technique was not significantly different from IS technique. Despite the higher failure loads associated with IS techniques in the present study, absolute peak load characteristics of DLSA were similar to previous studies. Hence, DLSA technique can be considered as a suitable alternative to IS fixation for biceps tenodesis

Critical shoulder angle (CSA), lateral acromial angle (LAA), and acromion index (AI) are common radiologic parameters used to distinguish between patients with rotator cuff tears (RCT) and those with an intact rotator cuff. This study aims to assess the predictive power of these parameters in degenerative RCT. This retrospective study included data from 92 patients who were divided into two groups: the RCT group, which included 47 patients with degenerative full-thickness supraspinatus tendon tears, and a control group of 45 subjects without tears. CSA, AI, and LAA measurements from standardized true anteroposterior radiographs were independently derived and analyzed by two orthopedic surgeons. Receiver operating characteristic (ROC) analyses were performed to determine the cutoff values. No significant differences were found between patients in the RCT and control groups in age (p = 0.079), gender (p = 0.804), or injury side (p = 0.552). Excellent inter-observer reliability was seen for CSA, LAA, and AI values. Mean CSA (38.1°) and AI (0.72) values were significantly larger in the RCT group than in the control group (34.56° and 0.67°, respectively, p < 0.001) with no significant difference between groups for LAA (RCT, 77.99° vs. control, 79.82°; p = 0.056). ROC analysis yielded an area under the curve (AUC) of 0.815 for CSA with a cutoff value of 37.95°, and CSA was found to be the strongest predictor of the presence of a RCT, followed by AI with an AUC of 0.783 and a cutoff value of 0.705. We conclude that CSA and AI may be useful predictive factors for degenerative RCT in the Turkish population

Abstract. Objectives. To evaluate mechanical properties of three suture-tendon constructs, the Krackow stitch (KS), the modified Prusik knot (PK) and the Locking SpeedWhip (LSW), using human cadaveric quadriceps grafts (QT). Methods. Thirty QT grafts were obtained from human cadaver specimens and an equal number of tendon-suture constructs were prepared for three stitches: KS, PK and LSW. The constructs were mounted in a materials testing machine (ElectroPuls E10000, Instron, Norwood, MA) and subject to tensile loading based on an established protocol. Load and displacement data for each tendon-suture construct were recorded. Results. Seven of 10 LSW specimens failed due to suture pullout before completing cyclic loading. Comparisons of the 3 successful LSW specimens (LSW3) were made to the KS and PK groups. All KS and PK specimens failed by suture breakage in load to failure stage. PK and LSW3 showed greater elongation after pretensioning than KS (7.29 ± 2.05, 7.05 ± 0.70, and 5.39 ± 0.95 mm respectively, p = 0.016 and p = 0.018). PK, LSW, and LSW3 showed greater elongation after preload than KS. Peak loads of PK (316.16 ± 18.31N), KS (296.00 ± 18.73N), and LSW (227.43 ± 76.20 N) were significantly different; LSW3 (319.33 ± 9.39 N) was not different from any group. KS was stiffer than PK (97.19 ± 8.03 vs 84.53 ± 6.72 N/mm, p = 0.0012). No differences were seen between the groups for elongation after cyclic loading or cross-sectional area. Conclusions. KS is the better of the sutured methods based on elongations and less risk of suture pullout. Excessive tendon tearing may initiate in the range of 100–200N with the LSW technique. PK provides similar performance to LSW and LSW3 in terms of elongations, but has the advantage of faster preparation time and less cost of the needle. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction. recent studies recognised metabolic abnormalities as additional factors in the development of rotator cuff (RC) tendinopathy. It has been hypothesised that the insertional area of this tendon is susceptible to degenerative changes due to intrinsic hypovascularization. The mechanisms underlying this process are not yet clear. In this study we attempted to confirm if larger lesions of the RC are related to impaired vasodilatatory response of the local circulation in conditions of “hemodynamic stress”. Patients & Methods. it was assumed that impaired vasal reaction to “hemodynamic stress” was a systemic condition. This phenomenon should therefore be not limited to the critical area of the tendon tear. Given this assumption post-ischemic vasodilation of brachial artery was studied through an echo-doppler (US) evaluation. 50 patients (mean 61 ± 4, range 50–65) all scheduled for surgical rotator cuff repair following a tendon tear, were enrolled. Three preoperative measurements of the brachial artery diameter before and after application of an ischemic band were collected. The size of the lesions was later assessed at the time of surgery. A statistical analysis was carried on to investigate the correlation between US assessment of brachial artery diameter and the corresponding size of the RC lesions. UCLA and ASES scores were also measured to assess clinical and functional outcomes. Results. Patients were classified into 4 groups according to Cofield's classification of tear size; respectively, 4 patients had massive lesions, 32 large, 10 medium and 4 had finally small lesions. The extent of the RC lesion showed an inverse correlation with the diameter of brachial artery after an ischemic stimulus: an increase in size of the lesion corresponded to lower mean post-ischemic diameter of the vessel (p <0.0001). UCLA and ASES data showed no statistically significant differences between the subgroups (p > 0.534). Discussion/Conclusion. It is not clear why the insertional area of tendons composing the RC is hypovascularised. We hypothesised there is an imbalance between local vasodilator and vasoconstrictor factors. The prevalence of vasoconstrictor substances determines a reduced post-ischemic vasodilation. The data presented provide the basis for the future identification of vascular impairment that could underlie the beginning of tendon degeneration in patients that are not yet affected by injury. This would be beneficial for effective prevention of this type of injury. An imbalance between vasodilator and vasoconstrictor factors could be the basis for vascular distress of RC eventually evolving into tendon lesions when other risk factors are associated. More specific vascular pathophysiological studies are however needed to further understand this mechanism and its potential in prevention of rotar cuff lesion

Introduction. Platelet Rich Plasma (PRP) is widely used in clinical praxis. Especially the effects in musculoskeletal repair studies are diverse and an augmentation of healing processes stays questionable. However, diverse cell culture studies reported promising results, which seem not be transferable into the clinical situation. We therefore performed a cell culture study which better reflects the clinical situation: the autologous stimulation of human tendon cells with PRP. Materials and Methods. Human tenocyte-like cells (hTLCs) from 24 donors (12 male/female) with supraspinatus tendon tears were isolated and characterized. The donors were grouped into 4 groups according to their age (</> 65 years) and sex. During follow up, approximately 2.5 years after initial surgery, the patients donated blood for PRP preparation (Ethic vote and written informed consent). Growth factors and platelets were quantified and the effect of autologous stimulation of the hTLCs was measured by analysis of cell proliferation, Collagen I synthesis and expression of Collagen I, III and Osteocalcin. Results. The platelet concentration for the 4 groups was between 3.6–4.5 × 10. 5. platelets/µl (reference level: 1.5–3×10. 5. platelets/µl blood). PRP contained high amounts of IGF-1, lower amounts of TGF-β1 and PDGF-AB. PDGF-AB concentration significantly correlated with platelet concentration and the TGF-β1 concentration. The amounts of BMP-7 and −12 were underneath the detection limits of the assays. Cell proliferation was positively affected by PRP exposure when compared to controls (2% FCS and 10% FCS) (p<0.05). However, the expression and synthesis of Collagen I was significantly reduced compared to controls. Collagen III expression was partly increased, while Osteocalcin expression was not affected. Discussion. PRP is a source of growth factors such as IGF-1, TGF-β and PDGF-AB. It has a high potential to stimulate cell proliferation, which might have a positive effect in clinical applications. However, the decreased expression and synthesis of Collagen I, the most important Collagen in the tendon, might explain the, to date, less satisfactory clinical results. PRPs might have their potential in chronic situation with pain reducing function rather than in acute healing situations. Further studies are necessary to better understand these mechanisms

Summary Statement. This study describes the design and preliminary in vitro testing of a novel patch for the repair of rotator cuff tendon tears. The laminated design incorporates woven and electrospun components. The woven element provides the patch with excellent mechanical strength and the electrospun layer improves cell attachment and promotes cell orientation and diferentiation. Introduction. Aligned nanofibrous electrospun scaffolds have been previously proposed as ideal scaffolds for tendon repair, replicating the anisotropy of tendon and providing a biomimetic design to encourage tissue regeneration (Hakimi et al., 2012). However, such scaffolds are still limited in terms of mechanical properties. This paper presents the design of a novel patch for rotator cuff repair in which the electrospun scaffold is supported by a woven component. Patients & Methods. Aligned polydioxanone (PDO) electrospun scaffolds were produced using a single nozzle electrospinning set-up with a rotating collector. The woven component was created by weaving PDO monofilaments with a manual loom. The woven and non-woven constituents were bound by a non-destructive method which preserves the surface morphology of the electrospun material. For each type of scaffold, a minimum of 3 specimens were tested to failure in tension using Zwick machine at rate of 0.3 mm/min until failure. For in vitro work, human-derived tendon cells were extracted from rotator cuff tendon tissue obtained during surgical repair, with appropriate ethical approval. Cells were cultured on the scaffolds for at least 14 days. Results. The contribution of the woven component to the tensile strength of the assembled patch is about 20 times more when compared to the electrospun scaffold. In vitro work shows that human tenocytes grown on the nanofibrous non-woven electrospun component align in the direction of the fibre orientation. The appearance of the woven component is shown. Discussion/Conclusion. While the woven component provides most of the mechanical strength, the aligned electrospun fibres enable cell orientation along the axis of the patch. These cells display a similar morphology to tenocytes in native tendons. With the combination of biomimetic features and good mechanical properties, this novel PDO patch is an excellent candidate material to support tendon repair

Improved understanding of the biomechanics and biology of rotator cuff tendons (RCT) may help reduce high re-rupture rates following repairs, particularly amongst larger tears. This study aims to use novel methods for quantitatively determining differences in the mechanical and thermal properties of intact healthy RCTs compared to torn ‘diseased’ tendons. A common problem in the mechanical testing of small tendon samples is that stress risers at the clamp-tendon interface can obscure measurements. As the shoulder is subject to shear, tension and compression, we developed a novel solution using Dynamic Shear Analysis (DSA), a form of rheology which studies material deformation. As collagen is the main component of RCT, the structure and mechanical properties may be affected by collagen conformational changes. Both dermis and rat tail tendon with increased collagen cross-linking exhibit stronger mechanical properties. Thermal changes detected by differential scanning calorimetry (DSC) can help to quantify collagen structural differences in torn RCT, and has been previously used to study muscle, cartilage and vertebral discs. There were 79 tears (mean age 65.2 years), which were classified according to the size of the tear as small, medium, large and massive. Two separate 3mm-sized biopsy samples were taken and subjected to DSA using oscillatory deformation under compression. The storage modulus (G') was calculated and used as an indicator of mechanical integrity. 18 control tendon specimens were obtained from patients aged between 22-89 years (mean age 58.8 years) during shoulder hemiarthroplasties and stabilisations. Additionally 7 normal, 7 small and 7 massive frozen specimens were thermally characterized. 3 samples per patient were heated between 20-80oC in hermetically sealed vessels. Useful thermal parameters were measured such as the melting temperature (TM) which apparently represents breaking of the amide-amide bonds and protein chains mobility, the denaturation temperature (TD) which supposedly corresponds to proteins falling out of solution and the denaturation enthalpy (ΔH) which reflects the relative amount of triple helical structure. Healthy tendons had a significantly higher modulus than torn tendons, indicating that torn tendons are mechanically weaker than normal tendons (p = 0.032). Normal tendons had significantly higher mean shear modulus than tendons with small and massive tears (p<0.01). Overall there was a negative correlation between moduli and severity of tendon tear (r = −0.698, p=0.189). The moduli did not significantly correlate with age, sex, hand dominance, or length of preservation in formalin. Massive RCT tears had significantly higher TM and TD when compared to normal RCT (p < 0.05), unlike small RCT tears. No significant difference was detected between the denaturation enthalpy of the different RCT groups. This case control study has demonstrated that normal RCTs have a significantly higher modulus than torn tendons, indicating that torn tendons have less mechanical integrity. Our study further demonstrated a trend between increasing tear size and decreasing mechanical integrity. This study has also demonstrated differences in some of the thermal properties of normal and torn RCTs. These are likely due to collagen structural changes. A decrease in the denaturation temperature of torn tendons, suggests that the material is intrinsically less stable. Torn tendons with reduced storage modulus and collagen integrity may be less able to withstand mechanical loads following repair. This pilot study provides some preliminary insight into the mechanisms that may contribute to, or represent adaptations to high rates of failure of RCT repairs

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

We released the infraspinatus tendons of six sheep, allowed retraction of the musculotendinous unit over a period of 40 weeks and then performed a repair. We studied retraction of the musculotendinous unit 35 weeks later using CT, MRI and macroscopic dissection.

The tendon was retracted by a mean of 4.7 cm (3.8 to 5.1) 40 weeks after release and remained at a mean of 4.2 cm (3.3 to 4.7) 35 weeks after the repair. Retraction of the muscle was only a mean of 2.7 cm (2.0 to 3.3) and 1.7 cm (1.1 to 2.2) respectively at these two points. Thus, the musculotendinous junction had shifted distally by a mean of 2.5 cm (2.0 to 2.8) relative to the tendon. Sheep muscle showed an ability to compensate for approximately 60% of the tendon retraction in a hitherto unknown fashion. Such retraction may not be a quantitatively reliable indicator of retraction of the muscle and may overestimate the need for elongation of the musculotendinous unit during repair.

We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts.

At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.

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.