Background: A gold standard treatment for articular cartilage injuries is yet to be found, and a cost‐effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies.Ideally, the animal model should allow for testing of clinically relevant treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies. This study aimed at verifying the Göttingen minipig as a pre‐clinical model for articular cartilage repair by testing existing clinical cartilage repair techniques and evaluating the use of two defects per knee.Methods: Sixteen fully mature Göttingen minipigs were used. The minipigs received bilateral trochlear osteochondral drill‐hole defects or chondral defects (Ø 6 mm), either one defect per knee or two defects per knee. The defects were treated with one of the following: Matrix‐induced autologous chondrocyte implantation (MACI), microfracture (MFx), autologous‐dual‐tissue transplantation (ADTT), autologous bone graft, autologous cartilage chips. Empty chondral and osteochondral defects were used as controls. MRI and CT were performed 3 and 6 month, histology was performed 6 month postoperative.Results: The repair tissue varied in morphology from non‐cartilaginous fibrous tissue to fibrocartilaginous tissue as seen on MRI, CT and histology at 6 month. The worst results were seen in the empty controls, while the best results were achieved with the MACI and ADTT treatment. The use of two defects per knee did not have any significant effect on the repair response.Conclusion: The outcomes of the applied treatments were consistent with the outcomes in clinical studies and it was possible to apply two defects per knee. The Göttingen minipig model was easy to handle, cost‐effective and provided predictable outcome. Based on this study the use of two defects per knee, one in the medial and one in the lateral trochlear facet, in male Göttingen minipigs is recommended.

Bertolotti’s syndrome (BS) refers to the possible association between the congenital malformation lumbosacral transitional vertebra (LSTV), and low back pain (LBP). Several treatments have been proposed including steroid injections, resections of the LSTV, laminectomy, and lumbar spinal fusion. The aim of this review was to compare the clinical outcomes in previous trials and case reports for these treatments in patients with LBP and LSTV. A PubMed search was conducted. We included English studies of patients diagnosed with LSTV treated with steroid injection, laminectomy, spinal fusion or resection of the transitional articulation. Of 272 articles reviewed 20 articles met the inclusion criteria. Their level of evidence were graded I–V and the clinical outcomes were evaluated. Only 1 study had high evidence level (II). The remainders were case series (level IV). Only 5 studies used validated clinical outcome measures. A total of 79 patients were reported: 31 received treatment with steroid injections, 33 were treated with surgical resection of the LSTV, 8 received lumbar spinal fusion, and 7 cases were treated with laminectomy. Surgical management seems to improve the patient’s symptoms, especially patients diagnosed with “far out syndrome” treated with laminectomy. Clinical outcomes were more heterogenetic for patient’s treated with steroid injections. The literature regarding BS is sparse and generally with low evidence. Non-surgical management (e.g., steroid injections) and surgical intervention could not directly be compared due to lack of standardization in clinical outcome. Generally, surgical management seems to improve patient’s clinical outcome over time, whereas steroid injection only improves the patient’s symptoms temporarily. Further studies with larger sample size and higher evidence are warranted for the clinical guidance in the treatment of BS.

Objective: To compare characteristics for patients scheduled for autologous chondrocyte implantation with matrix-assisted chondrocyte implantation (MACI) with those enrolled in clinical trials and to describe differences in patient selection between countries. Design: Anonymized data from patients scheduled for MACI treatment in the knee in Europe and Australia/Asia were obtained from the Genzyme/Sanofi database. Average age, defect size, and male-female ratio were analyzed and compared by country. Clinical cohort studies and prospective comparative trials using autologous chondrocyte implantation and related treatments were identified and weighted average age, weighted defect size, and male-female ratio were analyzed and compared with data from the database. Results: From the database 2,690 patients were included with mean age 33.7 years and male-female ratio of 67:33. Mean defect size was 5.64 cm² and 70% of the defects were 3 to 10 cm². There were significant differences between patients’ mean defect sizes between countries. Sixty-nine studies (57 cohorts and 12 prospective comparative trials) with a total of 5,449 patients were identified. The combined weighted mean age was 34.2 years, and the combined weighted mean defect size was 4.89 cm². Patients scheduled for MACI had significantly larger defects that those included in clinical trials. There was no significant difference in age. No differences were found between cohorts and prospective comparative trials. Conclusion: The vast majority of patients scheduled for autologous chondrocyte implantation with MACI have chondral defect comparable to that generally recommended, but differences exist between countries. Patients enrolled in clinical trials have significantly smaller defects than those undergoing treatment outside controlled trials.

The Bosworth fracture dislocation of the ankle is rare and present difficulties in treatment if not immediately recognized. Here we present two cases with pre- and postoperative x-rays and perioperative image of the dislocation. The fracture dislocations were further complicated by talocrural dislocations and were treated with open reduction and internal fixation.

Introduction: The adaptive response to systemic intermittent hypoxic therapy (SIHT) may be used for therapeutic advances due to the activation of multiple pathways involved in angiogenesis, immunomodulation, and tissue homeostasis. The aim of this study was to investigate the early age-dependent systemic response of different exposures of SIHT in mice. Materials and Methods: Sixty-four C57BL/6NRj female mice in three different age groups, young (4–5 weeks), adolescent (8–10 weeks), and adults (23–32 weeks), were exposed to SIHT. Different algorithms for equal hypoxic challenges (oxygen-decrease*time) were investigated to allow examination of the role of absolute hypoxia (oxygen-decrease) compared with relative hypoxia (total oxygen depletion over time). The systemic effects of angiogenetic regulation were investigated using blood samples analyzed by ELISA, proteome profiles, and proximity extension immunoassay. One-way analysis of variance with post hoc Bonferroni analyses was performed. Results: The early systemic response to SIHT was dependent on the absolute hypoxia rather than relative hypoxia over time. Serum erythropoietin (EPO) levels were increased significantly in young mice receiving low-oxygen SIHT treatments (10% and 15% oxygen). The expression of angiogenic proteins differed between the different age groups indicating an age-dependent response to SIHT. Focusing on hypoxia-inducible factor-1 (HIF-1) signaling, there was a trend toward upregulated angiogenetic response with younger age. Furthermore, clustering of protein expression in low-oxygen SIHT algorithms were found between young and adolescent mice. In adult mice, the majority of the proteins were downregulated as a response to SIHT. The systemic response of metabolites expressions was most pronounced in young mice. Systemic levels of cardiac troponin I (Tnni3) was unaffected by SIHT independent of age groups. Conclusions: The systemic response to SIHT is dependent on the absolute hypoxic exposure rather than the relative hypoxic depletion over time. Age-dependent effects of a short-term SIHT were associated with an increase in EPO, upregulation of angiogenetic pathways, and select metabolic and cell-surface proteins.

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33–36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week (p = 0.03) while a non-significant difference was observed after 4 weeks (p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.