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Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with diabetes have been reported to experience a higher prevalence of shoulder disorders compared to those without diabetes or with other medical conditions. However, the specific types of shoulder injuries and the extent of functional impairment associated with diabetes mellitus remain unclear. This study aimed to assess the association between diabetes and specific shoulder injuries, as well as the degree of functional impairment in affected patients. Methods: A case–control study was conducted involving 136 patients with shoulder functional impairment (UCLA Shoulder Scale ≤ 27). The study included 38 patients with diabetes and 98 non-diabetic controls. Shoulder injuries were diagnosed using ultrasonography, focusing on the supraspinatus tendon, long head of the biceps tendon, subscapularis tendon, and the presence of adhesive capsulitis or rotator cuff tears. Results: Diabetic patients had significantly higher rates of poor shoulder function compared to non-diabetic controls (89.47% vs. 63.26%, adjusted OR [adOR] 5.22, 95% CI 1.57–17.32, p = 0.007). While both groups had high rates of supraspinatus and long head of the biceps tendon injuries (~80%), no significant differences were found between them (p > 0.300). However, diabetic patients were more than three times as likely to have subscapularis tendon injuries (adOR 3.15, 95% CI 1.26–7.90, p = 0.014) and massive rotator cuff tears (adOR 3.76, 95% CI 1.16–12.15, p = 0.027). Additionally, diabetes was associated with a fourfold increased risk of adhesive capsulitis (adOR 4.16, 95% CI 1.20–14.47, p = 0.025). Conclusions: Diabetes mellitus is linked to greater functional and structural deterioration of the shoulder, highlighting the importance of considering diabetes as a risk factor for specific shoulder injuries. Early diagnosis and treatment may improve outcomes for diabetic patients with shoulder disorders.

Abstract Purpose Rotator Cuff (RC) lesions are classified in full-thickness and partial-thickness tears (PTRCTs). To our knowledge, no studies investigated the mean size of shoulder tendons in healthy and PTRCT patients using MRI scans. The aim of the study was to provide data to obtain and compare the mean value of tendon sizes in healthy and PTRCTs groups. Methods From 2014 to 2020, 500 were included in the study. They were divided into two groups: Group 1 (100 subjects) was composed of people positive for partial-thickness rotator cuff tears (PTRCTs), while the 400 subjects in Group 2 were negative for PTRCTs. Results Overall, of the patients included in the study, 231 were females and 269 were males. The mean age of the patients was 49 ± 12.7 years. The mean thickness of the supraspinatus tendon (SSP) was 5.7 ± 0.6 mm in Group 1, 5.9 ± 0.6 mm in Group 2 (p

Background: The incidence of rotator cuff tears is rapidly increasing, and operative techniques for rotator cuff repair have been developed. However, the rates of postoperative retear remain high. Purpose/Hypothesis: The purpose was to determine the effects of human dermal fibroblasts (HDFs) with hyaluronic acid (HA) on tendon-to-bone healing in a rabbit model of chronic rotator cuff tear injury. It was hypothesized that HA would enhance HDF proliferation and that a combination of HA and HDFs would produce a synergistic effect on the healing of repaired rotator cuff tendons of rabbits. Study Design: Controlled laboratory study. Methods: For in vitro study, HDFs were plated on a 24-well plate. After 1 day, 2 wells were designated as the test group and treated with 0.75% HA in phenol red–free Dulbecco's modified Eagle medium (DMEM). An other 2 wells served as control groups and were treated with the same volume of phenol red–free DMEM without HA. Each group was duplicated, resulting in a total of 4 wells, with 2 wells in each group for replication purposes. The cells were incubated for 24 hours, followed by 72-hour cultivation. Absorbance ratios at 96 and 24 hours were compared to evaluate cell proliferation. For the in vivo study, a total of 24 rabbits were randomly allocated to groups A, B, and C (n = 8 each). Supraspinatus tendons were detached bilaterally and left for 6 weeks to establish a chronic rotator tear model. Torn tendons were subsequently repaired using the following injections: group A, 0.5 × 106 HDFs with HA; group B, HA only; and group C, saline only. At 12 weeks after repair, biomechanical tests and histological evaluation were performed. Results: In vitro study showed that HDF proliferation significantly increased with HA (HDFs with HA vs HDFs without HA; 3.96 ± 0.09 vs 2.53 ± 0.15; P <.01). In vivo, group A showed significantly higher load-to-failure values than the other groups (53.8 ± 6.9 N/kg for group A, 30.6 ± 6.4 N/kg for group B, and 24.3 ± 7.6 N/kg for group C; P <.001). Histological evaluation confirmed that group A showed higher collagen fiber density and better collagen fiber continuity, tendon-to-bone interface maturation, and nuclear shape than the other groups (all P <.05). Conclusion: This controlled laboratory study verified the potential of the combination of HDFs and HA in enhancing healing in a chronic rotator cuff tear rabbit model. Clinical Relevance: A potential synergistic effect on rotator cuff tendon healing may be expected from a combination of HDFs and HA. [ABSTRACT FROM AUTHOR]

Purpose: Rotator Cuff (RC) lesions are classified in full-thickness and partial-thickness tears (PTRCTs). To our knowledge, no studies investigated the mean size of shoulder tendons in healthy and PTRCT patients using MRI scans. The aim of the study was to provide data to obtain and compare the mean value of tendon sizes in healthy and PTRCTs groups. Methods: From 2014 to 2020, 500 were included in the study. They were divided into two groups: Group 1 (100 subjects) was composed of people positive for partial-thickness rotator cuff tears (PTRCTs), while the 400 subjects in Group 2 were negative for PTRCTs. Results: Overall, of the patients included in the study, 231 were females and 269 were males. The mean age of the patients was 49 ± 12.7 years. The mean thickness of the supraspinatus tendon (SSP) was 5.7 ± 0.6 mm in Group 1, 5.9 ± 0.6 mm in Group 2 (p < 0.001). The mean length of the ISP tendon was 27.4 ± 3.2 mm in Group 1, 28.3 ± 3.8 mm in Group 2 (p = 0.004). The mean width of the SSP tendon was 17 ± 1.6 mm in Group 1, 17.6 ± 2 mm in Group 2 (p = 0.004). The mean width of the infraspinatus tendon (ISP) tendon was 17.7 ± 1.4 mm in Group 1, 18.3 ± 2.1 mm in Group 2 (p = 0.02). Conclusion: The anatomical data present in this paper may serve as a tool for surgeons to properly manage PTRCTs. The findings of the present study aimed to set the first step towards reaching unanimity to establish international cut-off values to perform surgery. Additionally, they could widely increase diagnostic accuracy, improving both conservative and surgical approaches. Lastly, further clinical trials using more accurate diagnostic MRI tools are required to better define the anatomical differences between PTRCT and healthy patients. Level of evidence: Level II, Retrospective Comparative Trial [ABSTRACT FROM AUTHOR]

PURPOSE:Quantitative imaging methods could improve diagnosis of rotator cuff degeneration, but the capability of quantitative MR and US imaging parameters to detect alterations in collagen is unknown. The goal of this study was to assess quantitative MR and US imaging measures for detecting abnormalities in collagen using an in vitro model of tendinosis with biochemical and histological correlation. METHOD:36 pieces of supraspinatus tendons from 6 cadaveric donors were equally distributed into 3 groups (2 subjected to different concentrations of collagenase and a control group). Ultrashort echo time MR and US imaging measures were performed to assess changes at baseline and after 24 h of enzymatic digestion. Biochemical and histological measures, including brightfield, fluorescence, and polarized microscopy, were used to verify the validity of the model and were compared with quantitative imaging parameters. Correlations between the imaging parameters and biochemically measured digestion were analyzed. RESULTS:Among the imaging parameters, macromolecular fraction (MMF), adiabatic T1ρ, T2*, and backscatter coefficient (BSC) were useful in differentiating between the extent of degeneration among the 3 groups. MMF strongly correlated with collagen loss (r=-0.81; 95% confidence interval [CI]: -0.90,-0.66), while the adiabatic T1ρ (r = 0.66; CI: 0.42,0.81), T2* (r = 0.58; CI: 0.31,0.76), and BSC (r = 0.51; CI: 0.22,0.72) moderately correlated with collagen loss. CONCLUSIONS:MMF, adiabatic T1ρ, and T2* measured and US BSC can detect alterations in collagen. Of the quantitative MR and US imaging measures evaluated, MMF showed the highest correlation with collagen loss and can be used to assess rotator cuff degeneration.

BackgroundRotator cuff tendons (RCTs) are challenging to image due to the "magic angle effect" and their short T2 .PurposeTo assess the degree of magic angle sensitivity of human RCTs and to utilize a 3D ultrashort echo time Cones sequence with magnetization transfer preparation (UTE-Cones-MT) and two-pool quantitative MT modeling with histological correlation. We hypothesized that MT parameters would be less sensitive to the magic angle compared with conventional T2 measurements.Study typeProspective imaging pathologic correlation.SpecimenTwenty cadaveric rotator cuff tendons were imaged at five sample orientations ranging from 0-90° relative to the B0 field.Field strength/sequence3T/3D UTE-Cones-MT and Carr-Purcell-Meiboom-Gill (CPMG).AssessmentTwo-pool quantitative MT modeling parameters and T2 values were calculated in regions of interest drawn by a medical physicist. Histopathological analysis was performed and mild and severe tendinopathy groups were assigned by a histopathologist and histotechnician.Statistical testsCoefficients of variations (CVs) were calculated for measures between the different orientations and group means were compared for each measure.ResultsCVs of T2 and macromolecular fractions between orientations were 26.14 ± 16.82% and 6.18 ± 2.77% (mean ± SD), respectively. T2 measurements at 0°, 27°, 70°, and 90° showed significant differences between the two histological groups (P = 0.004, 0.008, 0.003, and 0.015, respectively), but not at 55° (P = 0.611). Mean T2 value ranges between orientations for the mild and severe tendinopathy groups were 15.27-30.32 msec and 20.81-35.85 msec, respectively, showing overlap despite statistically significant differences (P = 0.003). Macromolecular fractions at all angles showed significant differences between the two groups (P < 0.0001). Mean fraction ranges between orientations for the mild and severe tendinopathy groups were 14.32-17.17% and 10.00-13.75% respectively (P < 0.0001) with no overlap.Data conclusionCompared with T2 , macromolecular fraction obtained with the 3D UTE-Cones-MT technique is resistant to the magic angle effect and is more sensitive to RCT degeneration.Level of evidence1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

Objectives: To reveal the possible relationship between greater tuberosity volume with rotator cuff tendon injuries. Materials and methods: In our study, the morphology of the greater tuberosity was evaluated retrospectively by using radiographs and MR images of 335 cases. While critical shoulder angle (CSA) was measured on radiographs, greater tuberosity (GT) area and volume were calculated, and also supraspinatus, infraspinatus, and teres minor tendons were evaluated, on MR images. The relationship of the measurements with the tendon injuries was analyzed statistically. Results: Among 188 female and 147 male patients, no statistically significant relationship was found between tendon injuries in terms of gender. The relationships between supra and infraspinatus tendon injuries and GT angle, area, and volume measurements were statistically significant. There was a statistically significant relationship between teres minor injury and GT angle, but no significant correlation with GT area and volume. Finally, there was no statistically significant correlation between all three tendon pathologies and CSA. Conclusion: Area, and especially volume measurements, which are morphological features of the GT, may reflect tendon damage without significant degenerative changes in the bone structure. In examinations before tendon damage progresses, GT volume is a morphological feature that needs to be evaluated and may facilitate early recognition of tendinopathies and be an early marker of rotator cuff injuries. [ABSTRACT FROM AUTHOR]

Abstract Background Rotator cuff tendon tears are typically degenerative and usually affect the region of tendon insertion on bone. The remnant torn tendon is degenerative and may not be an ideal source for progenitor cells for cell-based therapies. Therefore, the aim of this study was to determine if musculotendinous junction (MTJ), which is adjacent to tendon would be a viable alternate source of progenitor stem cells. We also sought to study the gene expression profile MTJ progenitors and compare it with progenitors isolated from RC tendon, RC muscle and other existing tissue sources (bone marrow, adipose tissue, and Achilles tendon). Methods Rotator cuff tendon (RCT), muscle (RCM), and RCMTJ as well as Achilles tendon (AT) tissues were harvested from healthy male Lewis rats and progenitor cultures were established from these tissues and also from bone marrow and adipose tissue. Quantitative RT-PCR was performed on RNA extracts from intact tissues and progenitor cells using a custom array for the mesenchymal stem cell (MSC) differentiation marker genes. The gene expression profile of MSC differentiation markers within four tissues types, six progenitor cells, and between tissue and their corresponding progenitors were compared. Results Progenitors cells can be isolated from rat rotator cuff musculotendinous tissue and their pattern of MSC gene expression was similar to the rotator cuff tendon progenitors for majority of the genes tested. However, there were significant differences between the MSC gene expression patterns of RCMTJ and RCM progenitors. Furthermore, there were differences in gene expression between the RCMTJ tissue and its progenitor cells with respect to MSC differentiation markers. The gene expression pattern of RCMTJ tissue was similar to RCM tissue with respect to markers of chondrogenesis, myogenesis, tenogenesis, and MSC specific markers. Conclusion We demonstrate that the musculotendinous junction contains distinct set of progenitor cells and their MSC gene expression pattern is similar to rotator cuff tendon progenitors. RCMTJ progenitors will be an attractive option for cell-based regenerative treatment of chronic rotator cuff tears.

Background: Owing to limited self-healing capacity, failure of rotator cuff tendon healing is a common complication after surgery. Biological scaffolds have garnered attention owing to their potential to enhance healing outcomes. Purpose: To verify the effect of the decellularized umbilical cord Wharton jelly (DUCWJ) scaffold as a bridging scaffold in a rabbit model of acute rotator cuff tendon defect. Study Design: Controlled laboratory study. Methods: We fabricated a DUCWJ scaffold using a physicochemical decellularized method, evaluating changes in the umbilical cord Wharton jelly before and after decellularization. Scanning electron microscopy and biomechanical testing were performed to determine the microstructure and mechanical properties. We assessed cytocompatibility and cell regulatory behavior of the scaffold toward tendon stem/progenitor cells (TSPCs). A supraspinatus tendon defect was created in 54 New Zealand White rabbits, allocated to the DUCWJ scaffold repair group and the negative control group (without scaffold). Histology, reverse transcription polymerase chain reaction, and biomechanical tensile strength were assessed at 4, 8, and 12 weeks postoperatively. Results: Decellularization completely removed cells from the umbilical cord Wharton jelly, retained a considerable amount of glycosaminoglycan and collagen, and preserved the microstructure and tensile strength. The DUCWJ scaffold facilitated migration and proliferation of TSPCs in vitro. Tendon-related gene expression revealed that the DUCWJ scaffold could maintain the tenocyte phenotype of TSPCs. In the in vivo study, the DUCWJ scaffold improved tendon healing and enhanced the biomechanical strength of repaired tendons. Histological evaluation scores of the DUCWJ group were significantly higher than those of the negative control at 4, 8, and 12 weeks after surgery (P <.05). In repaired tendon tissues, reverse transcription polymerase chain reaction findings revealed that the DUCWJ scaffold stimulated tendon development and maturation. Furthermore, an overall increase in ultimate load and tensile modulus was noted over time; the DUCWJ group presented better results than the negative control group (P <.05). Conclusion: The DUCWJ scaffold has an excellent 3-dimensional porous structure, good biocompatibility, and fundamental biomechanical characteristics, and it promotes migration, attachment, and proliferation of TSPCs. The in vivo animal study demonstrated that the DUCWJ scaffold has potential for tendon regeneration in an acute rotator cuff tendon defect model Clinical Relevance: DUCWJ scaffolds have potential as a regenerative material to augment rotator cuff healing in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Adipose stem cell–derived exosomes (ASC-Exos) are reported to effectively prevent muscle atrophy and degeneration of torn rat rotator cuff, but their influence on human samples and their potential mechanism are still unclear. Purpose: We aimed to investigate the effects of ASC-Exos on the metabolic activities of torn human rotator cuff tendons and explore the potential mechanism behind it. Study Design: Controlled laboratory study. Methods: Diseased supraspinatus tendons were harvested from 15 patients with a mean ± SD age of 65.8 ± 3.2 years who underwent reverse shoulder arthroplasty for chronic rotator cuff tears associated with glenohumeral pathological changes. Each tendon was dissected into 3 × 4 × 4–mm explants: the ones derived from the same tendon were placed into 12-well plates and cultured in complete culture media (control) or in complete culture media supplemented with ASC-Exos for 72 hours. Afterward, the concentrations of cytokines secreted into the culture media—including interleukin 1β (IL-1β), IL-6, IL-8, and matrix metalloproteinase 9 (MMP-9)—were measured using enzyme-linked immunosorbent assay (ELISA). Tendons were stained with hematoxylin and eosin and immunohistochemistry (type I and III collagens) for histological analyses. Moreover, the expression of anabolic genes (TIMP-1 and TIMP-3 ; type I and III collagen encoding) and catabolic genes (MMP-9 and MMP-13) in tendons were measured using real-time quantitative polymerase chain reaction. Phosphorylated AMPKα and Wnt/β-catenin pathways were assayed by western blotting to explore the potential mechanism of action of ASC-Exos. Results: Secretion of proinflammatory cytokines, including IL-1β, IL-6, and MMP-9, was significantly reduced in the ASC-Exos group as compared with the control group. Supraspinatus tendons in the ASC-Exos group exhibited superior histological properties, as demonstrated by higher tendon maturing scores and more type I collagen content, but there was no significant difference in type III collagen content between groups. Expression of MMP-9 and MMP-13 genes was decreased in the ASC-Exos group versus the control group. Increased expression of type I and III collagens and an elevated type I/III ratio were found in the ASC-Exos group when compared with the control group. There was no significant difference in the secretion of IL-8 and expression of TIMP-1 and TIMP-3 genes between the ASC-Exos and control groups. Western blotting revealed that ASC-Exos enhanced phosphorylated AMPKα and decreased β-catenin levels to prevent tendon degeneration. Conclusion: ASC-Exos maintained metabolic homeostasis of torn human rotator cuff tendons to improve their histological properties, which might be achieved by enhancing AMPK signaling to suppress Wnt/β-catenin activity. Clinical Relevance: ASC-Exos could be used as an effective biological tool to promote healing in torn human rotator cuff tendons. [ABSTRACT FROM AUTHOR]

Growth factor-mediated healing of rotator cuff tendon requires to develop a clinically applicable biomaterial playing roles of mechanical support and growth factor release in vivo. In this study, the alginate (AG) nonwoven-sponge composite scaffold (AGNWSP) was fabricated through the formation of an AG sponge layer on the AG nonwoven scaffold (AGNW) surface, and rotator cuff repair with the AG-based scaffolds containing transforming growth factor-beta 1 (TGF-β1) was investigated with a rabbit model. AGNWSP had higher tensile strength, lower bioabsorbability, and higher sustained TGF-β1 release capacity than AGNW, which were highly correlated with tendon regeneration. AGNW and AGNWSP were fixed to the ruptured tendon-to-bone sites, and fresh solutions of TGF-β1 were injected into the scaffolds. When AGNWSP was applied, the repaired supraspinatus tendon had higher ultimate failure load and stress. In addition, well-organized collagen fibers and fibrocartilages were observed at the tendon-to-bone interface in this case. It is suggested that high degree of ruptured rotator cuff healing could be achieved with AGNWSP in combination with TGF-β1. [ABSTRACT FROM AUTHOR]

Background: Rotator cuff tendon tears are typically degenerative and usually affect the region of tendon insertion on bone. The remnant torn tendon is degenerative and may not be an ideal source for progenitor cells for cell-based therapies. Therefore, the aim of this study was to determine if musculotendinous junction (MTJ), which is adjacent to tendon would be a viable alternate source of progenitor stem cells. We also sought to study the gene expression profile MTJ progenitors and compare it with progenitors isolated from RC tendon, RC muscle and other existing tissue sources (bone marrow, adipose tissue, and Achilles tendon).Methods: Rotator cuff tendon (RCT), muscle (RCM), and RCMTJ as well as Achilles tendon (AT) tissues were harvested from healthy male Lewis rats and progenitor cultures were established from these tissues and also from bone marrow and adipose tissue. Quantitative RT-PCR was performed on RNA extracts from intact tissues and progenitor cells using a custom array for the mesenchymal stem cell (MSC) differentiation marker genes. The gene expression profile of MSC differentiation markers within four tissues types, six progenitor cells, and between tissue and their corresponding progenitors were compared.Results: Progenitors cells can be isolated from rat rotator cuff musculotendinous tissue and their pattern of MSC gene expression was similar to the rotator cuff tendon progenitors for majority of the genes tested. However, there were significant differences between the MSC gene expression patterns of RCMTJ and RCM progenitors. Furthermore, there were differences in gene expression between the RCMTJ tissue and its progenitor cells with respect to MSC differentiation markers. The gene expression pattern of RCMTJ tissue was similar to RCM tissue with respect to markers of chondrogenesis, myogenesis, tenogenesis, and MSC specific markers.Conclusion: We demonstrate that the musculotendinous junction contains distinct set of progenitor cells and their MSC gene expression pattern is similar to rotator cuff tendon progenitors. RCMTJ progenitors will be an attractive option for cell-based regenerative treatment of chronic rotator cuff tears. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the biomechanical and histologic properties of rotator cuff repairs using a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA (poly(l -lactide- co -glycoside)) microfibers in an animal model compared to standard anchors in an ovine model. Fifty-six (n = 56) skeletally mature sheep were randomly assigned to a repair of an acute infraspinatus tendon detachment using a innovative anchor-PLGA scaffold device (Treatment) or a similar anchor without the scaffold (Control). Animals were humanely euthanized at 7 and 12 weeks post repair. Histologic and biomechanical properties of the repairs were evaluated and compared. The Treatment group had a significantly higher fibroblast count at 7 weeks compared to the Control group. The tendon bone repair distance, percentage perpendicular fibers, new bone formation at the tendon-bone interface, and collagen type III deposition was significantly greater for the Treatment group compared with the Control group at 12 weeks (P ≤.05). A positive correlation was identified in the Treatment group between increased failure loads at 12 weeks and the following parameters: tendon-bone integration, new bone formation, and collagen type III. No statistically significant differences in biomechanical properties were identified between Treatment and Control Groups (P >.05). Use of a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA microfibers improves the histologic properties of rotator cuff repairs in a sheep model. Improved histology was correlated with improved final construct strength at the 12-week time point. [ABSTRACT FROM AUTHOR]

Purpose: Neuronal theory regarding rotator cuff degeneration has developed from the findings that glutamate, an amino acid and an excitatory neurotransmitter, is present in increased concentrations in tendon tissues with tendinopathy and that glutamate induces cell death in fibroblasts of origin in rat supraspinatus tendon. The purpose of the current study was to determine whether N-acetylcysteine (NAC) has cytoprotective effects against glutamate-induced fibroblast death. Materials and Methods: Primary cultured fibroblasts were obtained from rat supraspinatus tendons. Varying concentrations of glutamate (0.5, 1, 5, and 10 mM) and of NAC (0.5, 1, 2, and 5 mM) were used for evaluation of cytotoxicity. Cell viability, cell cycles, types of cell death, intracellular ROS production, expressions of caspase-3/7, and Ca2+ influx were evaluated. Results: Glutamate significantly induced cell death, apoptosis, and Ca2+ influx and significantly increased caspase-3/7 activity and intracellular ROS production (p < 0.001). NAC significantly reduced the glutamate-induced cell death, apoptosis, Ca2+ influx, caspase-3/7 activity, and intracellular ROS production (p < 0.001). Conclusions: The glutamate-induced cytotoxic effects can be reduced by NAC, an antioxidant, through the reduction of intracellular oxidative stress and/or Ca2+ influx. [ABSTRACT FROM AUTHOR]

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy 3 2+ ) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.

The etiology of joint tissue degeneration following rotator cuff tear remains unclear. Thus, the purpose of this study was to understand the timeline of protease activity in the soft tissues of the shoulder (tendon, muscle, and cartilage) that may lead to down‐stream degeneration following rotator cuff tear. A well‐established rat model involving suprascapular nerve denervation and supraspinatus/infraspinatus tendon transection was employed. Histological staining and/or micro‐computed tomography (µCT) were used to observe structural damage in the supraspinatus tendon and muscle, humeral head cartilage, and subchondral bone. Multiplex gelatin zymography was utilized to assess protease activity in the supraspinatus tendon and muscle, and humeral head cartilage. Zymography analysis demonstrated that cathepsins were upregulated in the first week in all tissues, while MMP‐2 maintained prolonged activity in supraspinatus tendon between 1 and 3 weeks and increased only at 3 weeks in supraspinatus muscle. In supraspinatus tendon, increased cathepsin L and MMP‐2 activity in the first week was concurrent with matrix disorganization and infiltration of inflammatory cells. In contrast, significant upregulation of cathepsin L and K activity in supraspinatus muscle and humeral head cartilage did not correspond to any visible tissue damage at 1 week. However, focal defects developed in half of all animals' humeral head cartilage by 12 weeks (volume: 0.12 ± 0.09 mm3). This work provides a more comprehensive understanding of biochemical changes to joint tissue over time following rotator cuff tear. Overall, this provides insight into potential therapeutic targets and will better inform ideal intervention times and treatments for each tissue. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:490–502, 2019. [ABSTRACT FROM AUTHOR]

Rotator cuff tendons undergo degeneration with age, which could have an impact on tear propagation. The objective of this study was to predict tear propagation for different levels of tissue degeneration using an experimentally validated finite element model of a supraspinatus tendon. It was hypothesized that greater amounts of degeneration will result in tear propagation at lower loads than tendons with less degeneration. Using a previously-validated computational model of supraspinatus tendon, 1-cm tears were introduced in the anterior, middle, and posterior thirds of the tendon. Cohesive elements were assigned subject-specific failure properties to model tear propagation, and tendon degeneration ranging from "minimal" to "severe" was modeled by modifying its mechanical properties. Tears in tendons with severe degeneration required the smallest loads to propagate (122-207 N). Posterior tears required greater loads compared to middle and anterior tears at all levels of degeneration. Stress and strain required for tear propagation decreased substantially with degeneration, ranging from 8.5 MPa and 32.6% strain for minimal degeneration and 0.6 MPa and 4.5% strain for severe degeneration. Overall, this work indicates that greater amounts of tendon degeneration lead to greater risk of tear propagation, supporting the need for early detection and treatment of rotator cuff tears. [ABSTRACT FROM AUTHOR]

Over the past 25 years an increased appreciation of the positive impact of biologic interventions has driven significant advances in the surgical treatment of shoulder and knee conditions. These biologic adjuncts to treatment promote improved outcomes and have set the stage and increased research and development in this arena. [ABSTRACT FROM AUTHOR]

Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair. [ABSTRACT FROM AUTHOR]

Rotator cuff tears remain a significant clinical problem with a high incidence rate and severe clinical burden. Previous computational models developed to study rotator cuff tears have not modeled tissue damage and tear propagation. The objective of this study was to predict tear propagation for various combinations of tear size and location using an experimentally validated finite element model of supraspinatus tendon. It was hypothesized that larger rotator cuff tears propagate at lower loads than smaller tears, and that posterior tears require higher loads to propagate than anterior tears. Using a previously validated computational model of supraspinatus tendon, tears of size 0.5–1.5 cm were introduced to the tendon geometry in the anterior, middle, and posterior tendon thirds. Cohesive elements were assigned subject-specific failure properties and used to model tissue damage and tear propagation. A displacement of 5 mm was applied to the medial tendon edge to induce tear propagation. Model outputs included critical load required to propagate the tear, and principal stress and maximum principal strain at the anterior and posterior tear tips. For all tear sizes, posterior tears required the highest loads to propagate (247–567 N). Anterior tears generally required the least load to propagate (171–280 N). Stress and strain were larger on the articular side (maximum 33.9% articular strain vs 27.8% bursal strain). Overall, larger tears located in the anterior supraspinatus tendon that interrupt the rotator cable are most at risk for tear propagation, and should be carefully followed by clinicians when considering treatment options. [ABSTRACT FROM AUTHOR]

Injury of rotator cuff tendon is a common cause of pain and dysfunction of shoulder joint. The aim. of this study was to evaluate clinical efficiency of surgical treatment of patients with old total rupture of rotator cuff tendon. 63 patients were operated in clinic of Scientific Center of Reconstructive and. Restorative Surgery SB RAMS during 2007—2012. Average age of the patients was 47,6 ±2,1 years. Patients were randomized into two groups of clinical comparison. Patients of the first group had open reinsertion of rotator cuff tendons with transosseous sutures. Patients of the second group had the same procedure with use of an additional metal construction. The observation period differed from 3 months to 5 years (26 ± 5,1 months in average). As the result of the research positive results were in 83,1 % and 82,4 % of cases respectively at the assessment with use of UCLA scale. Reinsertion of full rupture of rotator cuff tendons in spite of risk of trauma of operative treatment is an operation. of choice that gives maximum prospects to the restoration of patients' capability. But analyzed technical defects of known methods caused the creation of a new method of surgical treatment of old injuries of rotator cuff tendon and. the device for its realization.