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

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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.]

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.

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