Effects of a graphene oxide-alginate sheet scaffold on rotator cuff tendon healing in a rat model.

BACKGROUND: Natural polymer scaffolds used to promote rotator cuff healing have limitations in terms of their mechanical and biochemical properties. This animal study aimed to investigate the effects of combined graphene oxide (GO) and alginate scaffold and the toxicity of GO on rotator cuff healing in a rat model. METHODS: First, the mechanical properties of a GO/alginate scaffold and a pure alginate scaffold were compared. The in vitro cytotoxicity of and proliferation of human tenocytes with the GO/alginate scaffold were evaluated by CCK-8 assay. For the in vivo experiment, 20 male rats were randomly divided into two groups (n = 10 each), and supraspinatus repair was performed: group 1 underwent supraspinatus repair alone, and group 2 underwent supraspinatus repair with the GO/alginate scaffold. Biomechanical and histological analyses were performed to evaluate the quality of tendon-to-bone healing 8 weeks after rotator cuff repair. RESULTS: The GO/alginate scaffold exhibited an increased maximum load (p = .001) and tensile strength (p = .001). In the cytotoxicity test, the cell survival rate with the GO/alginate scaffold was 102.08%. The proliferation rate of human tenocytes was no significant difference between the GO/alginate and alginate groups for 1, 3, 5, and 7 days. Biomechanically, group 2 exhibited a significantly greater ultimate failure load (p < .001), ultimate stress (p < .001), and stiffness (p < .001) than group 1. The histological analysis revealed that the tendon-to-bone interface in group 2 showed more collagen fibers bridging, tendon-to-bone integration, longitudinally oriented collagen fibers, and fibrocartilage formation than in group 1. CONCLUSION: A small amount of GO added to alginate improved the mechanical properties of the scaffold without evidence of cytotoxicity. At 8 weeks after rotator cuff repair, the GO/alginate scaffold improved tendon-to-bone healing without causing any signs of toxicity in a rat model.

Increased interleukin-6 and TP53 levels in rotator cuff tendon repair patients with hypercholesterolemia.

BACKGROUND: A previous study reported that hyperlipidemia increases the incidence of tears in the rotator cuff tendon and affects healing after repair. The aim of our study was to compare the gene and protein expression of torn rotator cuff tendons in patients both with and without hypercholesterolemia. METHODS: Thirty patients who provided rotator cuff tendon samples were classified into either a non-hypercholesterolemia group (n=19, serum total cholesterol [TC] <200 mg/dL) and hypercholesterolemia group (n=11, serum TC ≥240 mg/dL) based on their concentrations of serum TC. The expression of various genes of interest, including COL1A1, IGF1, IL-6, MMP2, MMP3, MMP9, MMP13, TNMD, and TP53, was analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot analysis was performed on the proteins encoded by interleukin (IL)-6 and TP53 that showed significantly different expression levels in real-time qRT-PCR. RESULTS: Except for IGF1, the gene expression levels of IL-6, MMP2, MMP9, and TP53 were significantly higher in the hypercholesterolemic group than in the non-hypercholesterolemia group. Western blot analysis confirmed significantly higher protein levels of IL-6 and TP53 in the hypercholesterolemic group (p<0.05). CONCLUSIONS: We observed an increase in inflammatory cytokine and matrix metalloproteinase (MMP) levels in hypercholesterolemic patients with rotator cuff tears. Increased levels of IL-6 and TP53 were observed at both the mRNA and protein levels. We suggest that the overexpression of IL-6 and TP53 may be a specific feature in rotator cuff disease patients with hypercholesterolemia.

Selective Serotonin Reuptake Inhibitor Promotes Bone-Tendon Interface Healing in a Rotator Cuff Tear Rat Model.

BACKGROUND: Selective serotonin reuptake inhibitor (SSRI) is believed to accelerate wound healing, and thus expected to have a positive effect on rotator cuff repair. We hypothesized that SSRI has a positive effect on the healing of the bone-tendon interface (BTI), and improved rotator cuff tear healing would be confirmed by mechanical strength measurements and histological assessment of the restored tendon. METHODS: The study used 40 adult male Sprague-Dawley wild-type rats. The animals were divided into two groups: group-SSRI, the supraspinatus repair with SSRI injection group, and group-C, conventional supraspinatus repair only without SSRI. Biomechanical and histological analyses were performed 8 weeks after index rotator cuff surgery. RESULTS: The ultimate load (N) was significantly higher in group-SSRI than in group-C (54.8 ± 56.9 Vs 25.1 ± 11.1, p = .031). In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 0.6 ± 0.5, group-SSRI: 1.1 ± 0.6, p = .024), vascularity (group-C: 0.1 ± 0.2, group-SSRI: 0.3 ± 0.4, p = .024) and cellularity (group-C: 1.7 ± 0.4, group-SSRI: 2.0 ± 0.0, p = .023) between the groups. Based on the total score, group-SSRI was significantly better compared with group-C (6.3 ± 2.7 Vs 4.3 ± 1.9, p = .019). CONCLUSION: Our study demonstrated that SSRI could facilitate improved biomechanical and histological outcomes 8 weeks after rotator cuff repair in a rat model. Consequently, SSRI may improve healing after rotator cuff repair.

Comparison of the Characteristics of Rotator Cuff Tissue in a Diabetic Rat Model.

This study evaluated the biomechanical and histologic characteristics of the rotator cuff tendon and muscle tissue with rat models with diabetes mellitus (DM) (group 1) and 30 male rats without DM (group 2). We conducted a time zero study without any additional procedures or external variables at 9 weeks after induction of the diabetic rat model. Thereafter, quantitative evaluation of advanced glycation end products (AGEs) was accomplished via enzyme-linked immunosorbent assay and immunohistochemistry (IHC). Fatty infiltration was investigated with Oil Red O staining, and the peroxisome proliferator activated receptor-gamma (PPAR-gamma) value was studied with IHC. Grossly, the supraspinatus tendons of the group 1 rats were more friable and discolored (yellowish) than those of group 2. In the biomechanical analysis, group 1 rats showed significantly inferior ultimate failure load (P=.001) and ultimate stress (P=.02). Group 1 was significantly inferior to group 2 in terms of total histologic scoring (P<.001). Mean AGE levels were significantly higher in group 1 (P<.001), as determined by IHC. In evaluating fatty infiltration, the degree of Oil Red O staining was significantly higher in group 1 (P<.001), but there was no significant difference in PPAR-gamma value between the 2 groups (P=.14). The intact rotator cuffs of rats with DM were associated with inferior biomechanics in association with AGE accumulation and increased fatty infiltration, as confirmed by histologic examination The hyperglycemic state caused by DM is associated with rotator cuff tendon degeneration. [Orthopedics. 2022;45(3):e154-e161.].

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model.

BACKGROUND: The healing failure rate after rotator cuff repair is considerably high. PURPOSE: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-ß1) on the sustained release of TGF-ß1 and rotator cuff healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A porous suture was developed, and its tensile strength was measured. TGF-ß1 was delivered using the porous suture, and a TGF-ß1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-ß1; and group 3, repair using the porous suture containing TGF-ß1. Eight weeks after repair, biomechanical and histological analyses were performed. RESULTS: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-ß1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). CONCLUSION: The porous suture containing TGF-ß1 could sustainedly and safely release TGF-ß1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. CLINICAL RELEVANCE: The porous suture containing TGF-ß1 might improve healing after rotator cuff repair.

Is a Local Administration of Parathyroid Hormone Effective to Tendon-to-Bone Healing in a Rat Rotator Cuff Repair Model?

To evaluate the effect of local parathyroid hormone (PTH) administration on rotator cuff tendon-to-bone healing in a rat model compared with systemic PTH injection and untreated controls. PTH-alginate scaffold was prepared and sustained release of PTH was confirmed. Bilateral supraspinatus tendon repairs were performed in 39 rats (group 1, supraspinatus repair only; group 2, supraspinatus repair with systemic PTH injection; group 3, supraspinatus repair with local PTH administration via an absorbable scaffold; n = 13 each). Biomechanical (cross-sectional area, mode of failure, load to failure, and ultimate stress: right side) and histological analyses (hematoxylin and eosin stain, Masson's Trichrome stain Picrosirius red stain, Immunohistochemistry for BMP2, PTH1R, ColI, and ColIII: Left side) were performed to evaluate tendon-to-bone healing quality at 8 weeks after repair, and blood test (osteocalcin and procollagen type I N-terminal pro-peptide [PINP] levels) was performed in all rats. There was no intergroup difference in the healing failure rate (p = 0.910) or failure mode (p = 0.585). Biomechanically, subjects in groups 2 and 3 exhibited significantly larger cross-sectional areas and higher ultimate failure loads and ultimate stress than those in group 1 (all p < 0.05); however, no differences were noted between groups 2 and 3 (all p > 0.05). Histologically, groups 2 and 3 exhibited more organized tendon-to-bone interface structures with higher density, parallel orientation, and collagen fiber continuity than group 1 (all p < 0.05 except collagen fiber continuity in group 1 vs. 2); however, no differences in histological parameters between groups 2 and 3 (all p > 0.05). The protein levels of bone morphogenic protein 2, PTH 1 receptor, and collagen I and III and the serum level of PINP were increased in groups 2 and 3 versus group 1 (all p < 0.05) without showing differences between groups 2 and 3 (all p > 0.05). Local PTH administration using an absorbable scaffold improved the biomechanical and histological outcomes of rotator cuff tendon-to-bone healing comparable with systemic PTH injection at 8 weeks after repair in a rat model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:82-91, 2020.

Electroencephalography in pediatric moyamoya disease: reappraisal of clinical value.

PURPOSE: The clinical value of electroencephalography (EEG) in pediatric moyamoya disease has been underestimated, though the characteristic patterns are well known. We undertook this study to evaluate the clinical value of EEG as a diagnostic and postoperative follow-up modality in pediatric moyamoya disease. METHODS: We retrospectively reviewed the pre and postoperative EEG with effective hyperventilation in 127 pediatric moyamoya patients and compared their patterns with hemodynamic images. RESULTS: One hundred and two patients (80.3 %) among 127 showed abnormal EEG findings before revascularization surgery. The typical rebuild-up phenomenon was observed in 82 (64.6 %) and localized build-up in 32 (25.2 %) without any significant clinical ischemic events during and after hyperventilation. The rebuild-up was observed more frequently in younger age groups (less than 13 years) and Suzuki stages III. The location of the rebuild-up distribution and asymmetric build-up was consistent with the area showing hemodynamic abnormalities on single photon emission computed tomography and/or perfusion magnetic resonance imaging. Postoperative follow-up EEGs were performed in 41 patients. Six patients with remaining rebuild-up in postoperative follow-up EEG showed poorer postoperative clinical outcomes. CONCLUSIONS: This study may reappraise EEG as an easy, safe, and adjunctive diagnostic and postoperative follow-up modality for evaluation of hemodynamic status and clinical outcome, especially in children with moyamoya disease.