Aims

Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration.

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

Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT. Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant. Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01). The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain. Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232)

Objectives. Indocyanine green (ICG) fluorescence angiography is an emerging technique that can provide detailed anatomical information during surgery. The purpose of this study is to determine whether ICG fluorescence angiography can be used to evaluate the blood flow of the rotator cuff tendon in the clinical setting. Methods. Twenty-six patients were evaluated from October 2016 to December 2017. The participants were categorized into three groups based on their diagnoses: the rotator cuff tear group; normal rotator cuff group; and adhesive capsulitis group. After establishing a posterior standard viewing portal, intravenous administration of ICG at 0.2 mg/kg body weight was performed, and fluorescence images were recorded. The time from injection of the drug to the beginning of enhancement of the observed area was measured. The hypovascular area in the rotator cuff was evaluated, and the ratio of the hypovascular area to the anterolateral area of the rotator cuff tendon was calculated (hypovascular area ratio). Results. ICG fluorescence angiography allowed for visualization of blood flow in the rotator cuff in all groups. The adhesive capsulitis group showed significantly earlier enhancement than the other groups. Furthermore, the adhesive capsulitis group had a significantly smaller hypovascular area ratio than the other groups. Conclusion. ICG fluorescence angiography allowed for evaluation of real-time blood flow of the rotator cuff in arthroscopic shoulder surgery. The techniques of ICG fluorescence angiography are simple and easy to observe, observer reliability is high, and it has utility for evaluating blood flow during surgery. Cite this article: N. Doi, T. Izaki, S. Miyake, T. Shibata, T. Ishimatsu, Y. Shibata, T. Yamamoto. Intraoperative evaluation of blood flow for soft tissues in orthopaedic surgery using indocyanine green fluorescence angiography: A pilot study. Bone Joint Res 2019;8:118–125. DOI: 10.1302/2046-3758.83.BJR-2018-0151.R1

Background. High re-rupture rates following repairs of rotator cuff tears (RCTs) have resulted in the increased use of repair grafts to act as temporary scaffolds to support tendon healing. It has been estimated that thousands of extracellular matrix repair grafts are used annually to augment surgical repair of rotator cuff tears. The only mechanical assessment of the suitability of these grafts for rotator cuff repair has been made using tensile testing only, and compared grafts to canine infraspinatus. As the shoulder and rotator cuff tendons are exposed to shearing as well as uniaxial loading, we compared the response of repair grafts and human rotator cuff tendons to shearing mechanical stress. We used a novel technique to study material deformation, dynamic shear analysis (DSA). Methods. The shear properties of four RCT repair grafts were measured (Restore, GraftJacket, Zimmer Collagen Repair and SportsMesh). 3mm-sized biopsy samples were taken and subjected to DSA using oscillatory deformation under compression to calculate the storage modulus (G') as an indicator of mechanical integrity. To assess how well the repair grafts were matched to normal rotator cuff tendons, the storage modulus was calculated for 18 human rotator cuff specimens which were obtained from patients aged between 22 and 89 years (mean age 58.8 years, with 9 males and 9 females). Control human rotator cuff tendons were obtained from the edge of tendons during hemiarthoplasties and stabilisations. A 1-way ANOVA of all of the groups was performed to compare shear properties between the different commercially available repair grafts and human rotator cuff tendons to see if they were different. Specific comparison between the different repair grafts and normal rotator cuff tendons was done using a Dunn's multiple comparison test. Results. We report a significant difference in the shear moduli of all four rotator cuff repair grafts (P<0.0001, 1 way ANOVA, Kruskall-Wallis test). 2 of the grafts, Zimmer Collagen Repair and SportMesh, were not significantly different when compared to rotator cuff tendons and were found to have comparable shear mechanical properties (P > 0.05, Dunn's multiple comparison test). The other repair grafts, GraftJacket and Restore, had a significantly lower storage modulus when compared to human rotator cuff tendons. Conclusions. With increasing numbers of repairs of rotator cuff tears, and augmentation of these repairs, there is a need to understand the mechanical and biological properties of the both repair grafts and the tendons they are designed to augment. At present there is no clear definition of the ideal mechanobiological properties of rotator cuff repair patches. Current rotator cuff repair grafts display a wide variation in their shear mechanical properties, and how closely they are matched to the mechanical properties of human rotator cuff tendons. It is hoped that this study may help to guide surgeons in deciding on the most appropriate rotator cuff tendon repair graft

Objectives . The effects of disease progression and common tendinopathy treatments on the tissue characteristics of human rotator cuff tendons have not previously been evaluated in detail owing to a lack of suitable sampling techniques. This study evaluated the structural characteristics of torn human supraspinatus tendons across the full disease spectrum, and the short-term effects of subacromial corticosteroid injections (SCIs) and subacromial decompression (SAD) surgery on these structural characteristics. . Methods . Samples were collected inter-operatively from supraspinatus tendons containing small, medium, large and massive full thickness tears (n = 33). Using a novel minimally invasive biopsy technique, paired samples were also collected from supraspinatus tendons containing partial thickness tears either before and seven weeks after subacromial SCI (n = 11), or before and seven weeks after SAD surgery (n = 14). Macroscopically normal subscapularis tendons of older patients (n = 5, mean age = 74.6 years) and supraspinatus tendons of younger patients (n = 16, mean age = 23.3) served as controls. Ultra- and micro-structural characteristics were assessed using atomic force microscopy and polarised light microscopy respectively. . Results. Significant structural differences existed between torn and control groups. Differences were identifiable early in the disease spectrum, and increased with increasing tear size. Neither SCI nor SAD surgery altered the structural properties of partially torn tendons seven weeks after treatment. . Conclusions . These findings may suggest the need for early clinical intervention strategies for torn rotator cuff tendons in order to prevent further degeneration of the tissue as tear size increases. Further work is required to establish the long-term abilities of SCI and SAD to prevent, and even reverse, such degeneration. Cite this article: Bone Joint Res 2014;3:252–61

INTRODUCTION. In order to address high failure rates following rotator cuff repairs, a greater understanding is required of the underlying structural changes so that treatments can be appropriately targeted and biomarkers of failure can be identified. As collagen is the primary constituent of tendon and determines force transmission, collagen structural changes may affect responses to loading. For example changes in collagen 1 and 5 are associated with the hyperelastic Ehlers-Danlos syndrome, which is diagnosed by looking for pathopneumonic altered collagen fibres or ‘collagen flowers’ in skin using transmission electron microscopy (TEM). To date no study has been performed on the microstructure of torn human rotator cuff tendons using TEM. It was hypothesized that normal, small and massive human rotator cuff tendons tears will have altered microscopic structures. The unique study aimed to use TEM to compare the ultrastructure of small and massive rotator cuff tears, to normal rotator cuff tendons. METHODS. Samples from 7 human rotator cuff tendons repairs were obtained, including 4 massive (>5 cm) and 3 small (< 1 cm) tears, and 3 matched normal controls with no history of connective tissue disorders. Specimens were fixed in 4% glutaraldehyde in 0.1M phosphate buffer, processed and examined blind using routine TEM examination. To assess whether changes in the relative expression of collagen 1 and 5 (COL1A1, COL5A1 and COL5A2) occurred in all tears, qPCR was performed on another 6 phenotypically matched patients. RESULTS. The basic structure of the normal tendon consisted of tightly packed clumps of dense packed parallel running collagen fibers with few fibroblasts and small amounts of fine filamentous material between clumps. In contrast, torn samples were more variable with areas of less dense packing of collagen fibers and larger areas of filamentous material plus variable numbers of lipid droplets both within the fibroblast and between the collagen bundles. There was also evidence of twisting and random orientation of individual collagen fibers. All torn tendons showed evidence of a proportion of the fibers within the collagen bundles being enlarged with a serrated outline, similar in appearance to ‘collagen flowers’. Clear differences between the small and massive tears were not identified. qRT-PCR of torn rotator cuff tendon specimens demonstrated no altered collagen expression compared to normal tendons. DISCUSSION. This novel study has identified the previously unreported presence of atypical collagen fibers with focal swelling resulting in the appearance of ‘collagen flowers’ in torn rotator cuff tendons only. This appearance is considered pathognomonic of Ehlers-Danlos syndrome, classical type 1 and 2. Torn tendons also showed an increase in filamentous material, and infiltration with fat droplets. These novel findings may offer insight into the mechanisms of structural damage that contribute to rotator cuff failure. Further examination is required, to evaluate the significance of these observations

Large and retracted rotator cuff tendon tears fail to repair, or re-tear following surgical intervention. This study attempted to develop novel tissue engineering approaches using tenocytes-seeded bioscaffolds for tendon reconstruction of massive rotator cuff tendon defect in rabbits. Porcine small intestine submucosa (Restore™) and type I/III collagen bioscaffold (ACI-MaixTM) were chosen as bioscaffold carriers for autologous tenocytes. Biological characterization of autologous tenocytes was conducted prior to the implantation. The tenocyte-seeded bioscaffolds were implanted as interposition grafts to reconstruct massive rotator cuff tendon defects in rabbits. In situ re-implantation of the autologous rotator cuff tendon, excised during defect creation served as a positive control. Histological outcomes were analysed and semi-quantitatively graded at four and eight weeks after surgery. The results demonstrate that at four weeks both tenocyte-seeded bioscaffolds display inflammatory reaction similar to bioscaffold-only cuff reconstruction and the histological grading were inferior to control repair. However, at eight weeks inflammatory reaction of both tenocyte-seeded bioscaffolds were dramatically reduced as compared to bioscaffold alone. In addition, bioscaf-folds seeded with tenocytes generated similar histological appearance to that of the positive control. The implantation of autologous tenocytes on collagen-based bioscaffold offers improved rotator cuff tendon healing and remodelling compared to the implantation of bioscaffold alone

Introduction Rotator cuff degeneration is considered to be a major factor in the pathogenesis of rotator cuff tendon tear. Degenerative weakening of the rotator cuff can result in irreversible complete cuff-tear arthropathy syndrome. Recently a porcine small intestinal submucosa (SIS) has been approved by TGA as biological implant for the repair of rotator cuff tendon tear. The aims of this study are to evaluate the safety and efficacy of SIS. Methods A commercial brand of SIS was examined by histology and PCR technique. The material was implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Next, we have used SIS to replace the rotator cuff tendon in rabbit (N=10) and compared to control (N=10). Histological examination was conducted at four and eight weeks after implantation. To further confirm if cells present in SIS material were of porcine origin, nested PCR for the amplification of DAP12 gene was used. Results Fresh SIS membrane before implantation contain multiple layers of spindle-shaped cells mixed with a small population of round-shaped cells. Chloroacetate esterase staining showed that the round-shaped cells are positive, indicating that they are mast cells. The tissue architecture of SIS mimics tendon structure as evidenced by H & E staining. The SIS membrane contained porcine DNA materials. Subcutaneous implant of SIS in mice (by six) for up to seven days showed no obvious inflammatory response or foreign body reaction. The result demonstrated that SIS has remained in the region and mixed with regenerative fibrous tissue after eight weeks. In some cases there was a massive recruitment of lymphocytes along the surface of membrane. However, no foreign body reactive giant cells were observed. Conclusions The result of this study indicated that SIS contains porcine cells and nucleic acid, which contradicts current views that SIS is a cell free biomaterial. Although no foreign body reaction of SIS was observed, SIS implant may cause chronic inflammation. Further studies should be conducted to confirm the clinical efficacy of SIS implant for rotator cuff tendon tear

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

This study aims to investigate the mechanical properties of a rotator cuff tear repaired with a polypropylene interposition graft in an ovine infraspinatus ex-vivo model. Twenty fresh shoulders from skeletally mature sheep were used in this study. A tear size of 20 mm from the tendon joint was created in the infraspinatus tendon to simulate a large tear in fifteen specimens. This was repaired with a polypropylene mesh used as an interposition graft between the ends of the tendon. Eight specimens were secured with mattress stitches while seven were secured to the remnant tendon on the greater tuberosity side by continuous stitching. Remaining five specimens with an intact tendon served as a control group. All specimens underwent cyclic loading with a universal testing machine to determine the ultimate failure load and gap distance. Gap distance increased with progressive cyclic loading through 3000 cycles for all repaired specimens. Mean gap distance after 3000 cycles for both continuous and mattress groups are 1.7 mm and 4.2 mm respectively (P = .001). Significantly higher mean ultimate failure load was also observed with 549.2 N in the continuous group, 426.6 N in the mattress group and 370 N in the intact group. The use of a polypropylene mesh as an interposition graft for large irreparable rotator cuff tears is biomechanically suitable and results in a robust repair that is comparable to an intact rotator cuff tendon. When paired with a continuous suturing technique, it demonstrates significantly resultant superior biomechanical properties that may potentially reduce re-tear rates after repairing large or massive rotator cuff tears

Introduction. The pathophysiology of high failure rates following rotator cuff tendon repairs, particularly massive tears, is not fully understood. Collagen structural changes have been shown to alter tendon thermal and mechanical properties. Thermal changes in small biopsies, detected by differential scanning calorimetry (DSC) can help to quantify collagen structural differences in torn rotator cuff tendons. This study aimed to form a quantitative rather than qualitative assessment, of whether differences in collagen structure and integrity existed between small biopsies of normal, small and massive rotator cuff tears using DSC. Methods. Thermal properties were measured for 27 human biopsies taken intra-operatively from normal, small, and massive rotator cuff tendon tears. 3 samples were taken from each patient and subjected to a modulated temperature ramp between 20–80°C at a rate of 2°C per minute with 0.318°C amplitude. The melting temperature (TM) is proposed to represent amide-amide hydrogen bond breakage and resulting protein backbone mobility. Denaturing temperature (TD) reportedly corresponds to the temperature at which the proteins fall out of solution. Denaturation enthalpy (H) should correlate with the amount of triple helical structure. Based upon a pre-study power calculation, this study had 90% power to detect a 10% difference in melting and denaturation temperature between groups with alpha=0.05. 1 specimen per patients was also frozen and cryosectioned and polarised light microscopy was used for quantitative validation. The effect of tear size on heat related parameters were performed using a one-way ANOVA test. A student's unpaired t-test was used to search for differences between individual groups (small tears, massive tears and normal tendons). Results. Small and massive rotator cuff tears had significantly higher melting temperature (TM), and denaturation enthalpy (H) compared to controls. The denaturing temperature (TD) was higher in the massive tears only compared to normal tears. No difference was detected between small and massive tears. Histology of massive tendon tears confirmed greater collagen structural disruption compared to small tears and controls. Conclusion. These novel findings suggest greater quantifiable collagen structural disruption in rotator cuff tears, compared to controls. A decrease in important thermal properties of torn tendons suggests that the material is intrinsically less stable. It is likely that torn tendons cannot withstand changes in temperature or stress as well as a perfect material could, particularly for massive tears which are more amenable to denaturation. This study offers insight into possible mechanisms for, or adaptation to, failure in tears and reduced strength

A prospective study was carried out to determine if recognised histological features seen at surgery could help predict those rotator cuff tendon repairs which re-ruptured. 40 rotator cuff tendon edge specimens from 40 patients’ shoulders were analysed histologically following routine mini-open rotator cuff repair. 32/40 underwent Ultrasonography, at a mean time of 35 months post-operatively, to determine repair integrity. The histological features seen at surgery were then compared to the repair integrity of the tendon from which it had been taken. Rotator cuff repairs that remained intact demonstrated a greater reparative response, in terms of increased fibrobast cellularity, cell proliferation and a thickened synovial membrane, than those repairs which reruptured. Larger tears which remained intact showed a higher degree of vasacularity and a significant inflammatory component than those that re-ruptured. Good tissue quality at the time of surgery allows the repair the best chance of remaining intact despite the size of the lesion. Routine histological analysis of the tissue biopsy, preformed in the post-operatively, can now aid the clinician in terms of early management and repair prognosis

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

Background. Rotator cuff tears pose a huge socioeconomic burden. Our study uses Fourier transform infrared spectroscopy (FTIR) as it is a quick, non-manipulative and non-destructive test, which can identify a wide range of chemical targets from small intraoperatively obtained specimens. The aim of this study was (i) to characterise the chemical and structural composition of rotator cuff tendons and (ii) to identify structural differences between anatomically distinct tear sizes. Such information may help to identify specific biomarkers of rotator cuff tear pathologies, which in turn could allow early identification and monitoring of disease progression. FTIR may provide insight into the different healing rates of different tear sizes. Methods. The infrared spectra of 81 torn rotator cuff tendons were measured using a FTIR spectrometer. The rotator cuff tear sizes were classified as partial, small, medium, large and massive, and compared to 14 normal controls. All spectra were classified using standard multivariate analysis; principal component analysis, partial least square and discriminant function analysis. Results. FTIR readily differentiated between normal and torn tendons, and different tear sizes. We identified the key discriminating molecules and spectra altered in torn tendons as: (i) carbohydrates/phospholipids (1030-1200 cm. -1. ), (ii) collagen (1300-1700, 3000-3350 cm. -1. ) and (iii) lipids (2800-3000 cm. -1. ). Partial tears were chemically distinct from normal and small tears, and primarily involved a reduction in collagen type II. Conclusion. This study has demonstrated that FTIR can identify different sizes of rotator cuff tear based upon distinguishable chemical and structural features. The onset of rotator cuff tear pathology is mainly due to alterations of the collagen structural arrangements, with associated changes in lipids and carbohydrates. The approach described is rapid and has the potential to be used intraoperatively to determine the quality of the tendon and extent of disease, thus guiding surgical repairs or for monitoring of treatments

Introduction and Aims: Treatment of rotator cuff tendon tear presents a significant therapeutic challenge to surgeons. Porcine small intestinal submucosa (SIS) is a biomaterial approved by TGA and FDA for the repair of rotator cuff tendon tear. The aims of this study are to evaluate the safety and efficacy of SIS. Method: SIS purchased from DePuy Johnson & Johnson was examined by histology and PCR technique. The material was also implanted into mice and rabbits for the evaluation of biological reaction and inflammatory response. Porcine immunoreceptor DAP12 gene was used to examine if the material contained porcine DNA. Results: Fresh SIS membrane before implantation contains multiple layers of spindle-shaped cells mixed with a small population of round-shaped cells. Chloro-acetate esterase staining showed that the round-shaped cells are positive, indicating that they are mast cells. The tissue architecture of SIS mimics to tendon structure as evidenced by H& E staining. To further confirm if cells present in SIS material were porcine origin, nested PCR for the amplification of DAP12 gene was used. The result demonstrated that SIS membrane contain porcine DNA materials. Conclusion: SIS contains porcine cells and nuclei acid, which contradicts with current views that SIS is a cell-free biomaterial. Although no foreign body reaction of SIS was observed, SIS implant may cause chronic inflammation. Further studies should be conducted to confirm the clinical efficacy of SIS implant

Aims: The aim of the study was to investigate the cap-suloligamentous structures of the shoulder joint and their association with rotator cuff tendons. Methods: Twenty seven alcohol-formalin-glycerol þxed right shoulder joints (age range 65 Ð 78 years) were investigated. The Ligg. coracohumerale, coracoglenoidale, glenohumeralia, semicirculare humeri and gleno-capsulare were dissected in þne detail. To visualise the rotator interval, the Processus coracoideus was cut at its base and moved together with the Ligg. coracohumerale and coracoglenoidale posteriorly. The analysis of the ligamentous structures and their relations with the rotator cuff tendons was performed. Results: The Lig. coracohumerale originated from Processus coracoideus and Lig. coracoglenoidale. It inserted into the Lig.semicirculare humeri Ð a capsular ligament spread between Tubercula minus et majus. Lig. glenocapsulare originated posterior to the Tuberculum supragle-noidale and inserted into the Lig. semicirculare humeri. The Mm. supra- and infraspinatus inserted into the Lig. semicirculare humeri. The anterior capsule was strengthened in addition to the three Ligg. glenohumeralia with a Lig. glenohumerale spirale. It originated from the Tuberculum infraglenoidale, coursed craniolaterally and inserted together with the M. subscapularis tendon at the Tuberculum minus. Conclusions: The shoulder joint capsule is strengthened with the Ligg. coracohumerale, coracoglenoidale, glenohumeralia superior, medium, inferior et spirale and Ligg. semicirculare humeri et glenocapsulare. The close relation of the ligamentous structures with the tendons of the rotator cuff brings a new insight into the different glenohumeral pathologies

Introduction: New biotechnologies create opportunities for gene therapy to promote rotator cuff healing. We have previously demonstrated that genetically engineered mesenchymal stem cells (MSCs) over expressing BMP-2 and SMAD8 signaling molecule differentiate to tenocytes in vitro and in vivo. Therefore, we hypothesized that rotator cuff defect could be regenerated using genetically engineered MSCs. Method: Nonviral methods were utilized to establish genetically engineered MSCs that co-express BMP-2 and the Smad8 signaling molecule. A previously validated animal model was utilized to examine rotator cuff healing. A 2mm x2mm full thickness defect was created in the infraspinatus tendon of 8 nude rats. A collagen-I biomembrane (TissueMend) containing 3 x 10. 6. engineered cells was sewn into the defect. An identical control procedure was repeated on the contralateral side with biomembrane containing non-engineered MSCs. Results: 4 weeks post implantation the area of implantation was isolated and analyzed by light microscopy and histochemical staining. Analysis of the engineered implants revealed the formation of dense connective tissue with parallel-organized fibers and spindle shaped cells, unlike the control samples. Proton Double Quantum Filtered Magnetic Resonance Imaging technique of the rotator cuff tendons demonstrated an increased presence of organized collagen fibers within the engineered rotator cuff tissue when compared with either native rotator cuff or those treated with non-engineered MSCs. Conclusion: This is the first report showing rotator cuff tendon repair using genetically engineered MSCs. Moreover these findings may have considerable importance for tendon healing and may indicate a clinical gene therapy platform to augment surgical repair

Aim To determine if tissue metabolism varies in supraspinatus tendons with distance from the edge of the rotator cuff tendon tear and also with differing size of tear. Background Tissue metabolism can be assessed by measuring oxygen and nitrous oxide concentrations within the tissue. Viable tendon tissue consumes oxygen and contains nitrous oxide (used in the general anaesthetic) from the blood stream. Non-viable tendon tissue will not consume oxygen but will contain nitrous oxide. Methods Oxygen and Nitrous Oxide concentrations were measured amperometrically using silver needle microelectrodes. The needle was inserted into the supraspinatus tendon of patients with massive, large, medium and small full thickness rotator cuff tears and patients with partial thickness and no tears. Patients undergoing open stabilisation were used as controls. Measurements were made at a number of quantifiable points from the tendon edge to allow the creation of a topographical map of tissue metabolism. Oxygen consumption was calculated using measured oxygen and nitrous oxide levels at each point. Results In patients with rotator cuff tears oxygen consumption was significantly lower near to the edge of the tear. Patients with impingement syndrome but no evidence of a rotator cuff tear also showed a decreased level of oxygen consumption in the anterior part of supraspinatus, but this was significantly higher than the levels seen in the torn tendon. The control group showed no significant alteration in oxygen levels. Conclusion Patients with rotator cuff tendon tear demonstrate significantly reduced levels of tissue metabolism. This reduction in tissue viability is significantly greater at the edge of the tear and in larger tears. Patients with intact tendons and impingement syndrome also demonstrate minor reduction in tissue tendon viability compared with controls

Rotator cuff tears are a common cause of shoulder pain and dysfunction. Therefore, the purpose of this in-vitro biomechanical study was conducted to determine the effects of simulated tears and subsequent repairs of the rotator cuff tendons on joint kinematics. Eight paired fresh-frozen cadaveric shoulder specimens (mean age: 66.0 ± 8.7 years) were tested using a custom loading apparatus designed to simulate unconstrained motion of the humerus. Cables were sutured to the rotator cuff tendons and the deltoid. Loads were applied to the cables based on variable ratios of electromyographic (EMG) data and average physiological cross-sectional area (pCSA) of the muscles. An electromagnetic tracking device (Flock of Birds, Ascension Technologies, VT) was used to provide real-time feedback of abduction angle, to which the loading ratio was varied correspondingly. 2 and 4cm tears were made starting at the rotator cuff interval and extending posteriorly. Specimens were randomised to receive either single or double suture anchor repair. In order to quantify repeatability, five successive tests on each of the intact, torn, and repaired cases were performed. Statistical significance was established using One- and Two-way Repeated Measured ANOVAs (p< 0.05). Rotator cuff tears caused alteration in glenohumeral kinematics. A 2cm tear caused the humerus to consistently move posterior through the arc of abduction; however, as the tear increased to 4cm the humerus moved anteriorly, returning towards the intact state. Double row suture anchor repairs more accurately reproduced the kinematics of the intact specimen compared to single row suture anchor repair. The initial posterior displacement in the plane of elevation with the sectioning of the supraspinatus is related to the diminished anterior moment on the glenohumeral joint. As the tear proceeds into the infraspinatus, the anterior and posterior forces become more balanced and a return to near normal intact kinematics was observed. This study demonstrates that double row suture anchor repair more accurately reproduces active shoulder kinematics of the intact shoulder specimens