Tendon rupture induces an inflammatory response characterized by release of pro-inflammatory cytokines and impaired tendon performance. This study sought to investigate the therapeutic effects of simvastatin-loaded porous microspheres (SIM/PMSs) on inflamed tenocytes in vitro and collagenase-induced Achilles tendinitis in vivo. The treatment of SIM/PMSs in lipopolysaccharide (LPS)-treated tenocytes reduced the mRNA expressions of pro-inflammatory cytokines (Matrix metalloproteinase-3 (MMP-3), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). In addition, the local injection of SIM/PMSs into the tendons of collagenase-induced Achilles tendinitis rat models suppressed pro-inflammatory cytokines (MMP-3, COX-2, IL-6, TNF-α, and MMP-13). This local treatment also upregulated anti-inflammatory cytokines (IL-4, IL-10, and IL-13). Furthermore, treatment with SIM/PMSs also improved the alignment of collagen fibrils and effectively prevented collagen disruption in a dose-dependent manner. Therefore, SIM/PMSs treatment resulted in an incremental increase in the collagen content, stiffness, and tensile strength in tendons. This study suggests that SIM/PMSs have great potential for tendon healing and restoration in Achilles tendinitis.

Because Mg-Ca-Zn alloys are biodegradable and obviate secondary implant removal, they are especially beneficial for pediatric patients. We examined the degradation performance of Mg-Ca-Zn alloys depending on the surface modification and investigated the in vivo effects on the growth plate in a skeletally immature rabbit model. Either plasma electrolyte oxidation (PEO)-coated (n = 18) or non-coated (n = 18) Mg-Ca-Zn alloy was inserted at the distal femoral physis. We measured the degradation performance and femoral segment lengths using micro-CT. In addition, we analyzed the histomorphometric and histopathologic characteristics of the growth plate. Although there were no acute, chronic inflammatory reactions in either group, they differed significantly in the tissue reactions to their degradation performance and physeal responses. Compared to non-coated alloys, PEO-coated alloys degraded significantly slowly with diminished hydrogen gas formation. Depending on the degradation rate, large bone bridge formation and premature physeal arrest occurred primarily in the non-coated group, whereas only a small-sized bone bridge formed in the PEO-coated group. This difference ultimately led to significant shortening of the femoral segment in the non-coated group. This study suggests that optimal degradation could be achieved with PEO-coated Mg-Ca-Zn alloys, making them promising and safe biodegradable materials with no growth plate damage.

Background: Endocrinopathy is a risk factor for slipped capital femoral epiphysis (SCFE). We aimed to determine (1) the incidence of endocrinopathy-associated SCFE compared with that of non-endocrinopathy-associated SCFE, (2) whether the incidence of SCFE increases with the number of deficient hormones, and (3) the clinical characteristics of endocrinopathy-associated SCFE. Methods: We conducted a population-based cohort study using a nationwide database in South Korea. All new diagnoses of endocrinopathy or SCFE between 2002 and 2019 in children born between 2002 and 2005 were identified. The incidence of SCFE was calculated for each type of endocrinopathy. The trend of the incidence of SCFE relative to the number of deficient hormones was analyzed. The male:female ratio was compared between endocrinopathy-associated SCFE and non-endocrinopathy-associated SCFE. For endocrinopathy-associated SCFE, the time between the diagnoses of SCFE and endocrinopathy was evaluated. Results: The incidence of SCFE was higher in children with endocrinopathy than in those without endocrinopathy (37.1/100,000 versus 9.0/100,000 children) (relative risk, 4.1 [95% confidence interval, 2.8-6.1]). Among various endocrinopathies, growth hormone deficiency showed the highest incidence of SCFE (583.8/100,000 children). The Cochran-Armitage test showed a linear trend, with an increased number of deficient hormones being associated with a higher incidence of SCFE (p < 0.001). Male sex was dominant in the non-endocrinopathy-associated SCFE group (73%; 117 of 161), whereas female sex was dominant in the endocrinopathy-associated SCFE group (53%; 16 of 30) (p = 0.009). Twenty-two of the 30 cases of endocrinopathy-associated SCFE were diagnosed after the diagnosis of endocrinopathy, with a median time of 3.6 years between the diagnoses. Six (27%) of these 22 children developed SCFE >5 years after the diagnosis of endocrinopathy. Conclusions: The incidence of SCFE was approximately 4 times higher in children with endocrinopathy than in those without endocrinopathy. The risk of SCFE increased with an increased number of deficient hormones. Long-term monitoring of SCFE occurrence in children with endocrinopathies is strongly recommended. Level of Evidence: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Having observed a tendency towards femoral overgrowth (FO) of the affected limb in children with atrophic-type congenital pseudarthrosis of the tibia (CPT), we aimed to identify the incidence of, contributors to, and patterns of FO among such children. We retrospectively evaluated 55 children with CPT, 22 with prepseudarthrosis and 33 with atrophic-type CPT from 1989 to 2012. FO was defined as an affected femoral segment ≥10 mm longer than the contralateral segment. We investigated FO incidences in prepseudarthrosis versus atrophic-type CPT. Sex, laterality, coexistence of neurofibromatosis type 1, development of frank pseudarthrosis, extent of tibial shortening, shortening in foot height, deformity severity, distraction osteogenesis (DO) treatment, refracture, increased femoral neck-shaft angle, tibiofemoral angle, and ankle valgus angle were investigated to identify potential contributors to FO. Patterns of FO were also determined. At initial presentation, 11 patients exhibited a mean of 13 mm (10–23) of FO. However, the nature of FO changed over time during the follow-up period (mean, 10.8 years; range, 4.3–19.3). At the last follow-up, 14 patients presented with a mean of 12 mm (10–18) of FO. With the exception of one patient, all patients with FO presented with atrophic-type CPT. Frank pseudarthrosis, DO treatment, and increased femoral neck-shaft angle were significantly associated with FO (p = 0.016, p = 0.001, and p = 0.005, respectively). Diverse patterns of FO were observed. FO of the affected limb is frequently encountered in patients with atrophic-type CPT. A compensatory response to frank pseudarthrosis, DO treatment, and neurofibromatosis may play a role in the diverse patterns of FO.

Achilles tendinitis caused by overuse, aging, or gradual wear induces pain, swelling, and stiffness of Achilles tendon and leads to tendon rupture. This study was performed to investigate the suppression of inflammation responses in interleukin‐1β- (IL‐1β-) stimulated tenocytes in vitro and the suppression of the progression of Achilles tendinitis‐induced rat models in vivo using dexamethasone‐containing porous microspheres (DEX/PMSs) for a sustained intratendinous DEX delivery. DEX from DEX/PMSs showed the sustained release of DEX. Treatment of IL‐1β‐stimulated tenocytes with DEX/PMSs suppressed the mRNA levels for COX‐2, IL‐1β, IL‐6, and TNF‐α. The intratendinous injection of DEX/PMSs into Achilles tendinitis rats both decreased the mRNA levels for these cytokines and increased mRNA levels for anti‐inflammatory cytokines IL‐4 and IL‐10 in tendon tissues. Furthermore, DEX/PMSs effectively prevented tendon degeneration by enhancing the collagen content and biomechanical properties. Our findings suggest that DEX/PMSs show great potential as a sustained intratendinous delivery system for ameliorating inflammation responses as well as tendon degeneration in Achilles tendinitis.

In this study, we created an inclusion nanocarrier of icariin (ICA) and β-cyclodextrin-alginate conjugate (ICA/β-CD-ALG) and determined its in vitro osteogenic ability on MC3T3-E1 cells. The morphological shape of the prepared β-CD-ALG with or without ICA was nano-sized and round. The use of β-CD-ALG achieved a sustained ICA release for up to 7 days. In vitro studies found that ICA/β-CD-ALG had a greater potential in osteogenesis on MC3T3-E1 cells compared to β-CD-ALG by exhibiting both higher alkaline phosphatase levels and the amount of calcium deposits. Moreover, ICA/β-CD-ALG greatly increased the levels of osteogenesis markers including osteocalcin (OCN) and osteopontin (OPN). Our results suggest that ICA/β-CD-ALG plays a significant role in cellular osteogenic activity.