Background: Synovial mesenchymal stem cells (SMSC) possess a high chondrogenic differentiation potential, which possibly supports natural and surgically induced healing of cartilage lesions. We hypothesized enhanced chondrogenesis of SMSC caused by the vicinity of chondrocytes (CHDR). Methods: Human SMSC and CHDR interactions were investigated in an in-vitro trans-well monolayer coculture over a time period of up to 21 days. Protein expression was analyzed using histology, immunostaining, or enzyme-linked immunosorbent assay. Additionally, mRNA expression was assessed by quantitative PCR. Results: After 7 days, phase-contrast microscopy revealed cell aggregation of SMSC in coculture with CHDR. Afterwards, cells formed spheres and lost adherence. However, this phenomenon was not observed when culturing SMSC alone. Fluorescence labeling showed concurrent collagen type II expression. Addition of transforming growth factor beta (TGFβ) to the cocultures induced SMSC aggregation in less time and with higher intensity. Additionally, alcian blue staining demonstrated enhanced glycosaminoglycan expression around SMSC aggregates after 1 and 2 weeks. Although TGFβ mRNA was expressed in all SMSC, the protein was measured with constantly increasing levels over 21 days only in supernatants of the cocultures. Considering the enhanced mRNA levels following supplementation with TGFβ, a positive feedback mechanism can be supposed. In line with the development of a chondrogenic phenotype, aggrecan mRNA expression increased after 7 and 14 days in the cocultures with and without TGFβ. Coculture conditions also amplified collagen type II mRNA expression after 2 weeks without and already after 1 week with TGFβ. There was no difference in collagen type I and type X expression between SMSC alone and the coculture with CHDR. Expression of both collagens increased following addition of TGFβ. mRNA data correlated with the intensity of immunofluorescence staining. Conclusions: Paracrine effects of CHDR induce a chondrogenic phenotype in SMSC possibly mimicking joint homeostasis. Coculture approaches may lead to a better understanding of cellular interactions with potential implications for cartilage repair procedures.

Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. 232 patients treated for bony lesions with ACB (n = 116) or SBS (n = 116) within a 10-year time period were included in this case–control study. Furthermore, both materials were seeded with human osteoblasts (hOB, n = 10) and analyzed by histology, for viability (AlamarBlue®) and protein expression activity (Luminex®). The complication rate was 14.2 %, proportion of defects without bony healing 3.6 %; neither outcome parameter differed comparing the intervention groups. Failed consolidation correlated with an increase in complications (p < 0.03). The rate of complications was further highly significant in association with the location of use (p < 0.001), but did not depend on age, ASA risk classification, BMI, smoking behavior or type of insurance. However, those factors did significantly influence the bony healing rate (p < 0.02). Complication and consolidation rates were independent of gender and the filling substances employed within the different locations. Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We observed initially increased expression of osteocalcin, osteopontin, and osteoprotegerin as well as leptin and adiponectin secretion declining after 1 week, especially in the ACB group. Although both investigated materials appeared to be similarly suitable for the treatment of skeletal lesions in-vivo and in-vitro, outcome was decisively influenced by other factors such as the site of use or epidemiological parameters.

The aim of this study is to systematically review the literature on clinical outcomes of patients who have undergone autologous matrix-induced chondrogenesis (AMIC) for treatment of osteochondral lesions of the talus (OCL) and compare the studies' outcomes. Pubmed and Embase were searched in January 2020 for articles concerning OCL surgery. Studies were included if they had a minimum 1-year follow-up and the primary measures were functional outcomes. The meta-analysis compared the Visual Analogic Score (VAS), the American Orthopedic Foot and Ankle Score (AOFAS), and the Foot Function Index (FFI) between baseline and follow-up of 1-2years, and 3-5years. A random effects model was used to evaluate outcome changes. The search returned 15 studies, with a total of 492 patients. The VAS improved 4.45 and 4.6 points from baseline to the 1-2year and 3-5yearfollow-up, respectively (p<0.001). AOFAS improved 31.59 and 32.47 points from baseline to the 1-2year and 3-5yearfollow-up, respectively (p<0.001). The FFI showed a significant improvement of 30.93 points from baseline to year 3-5 (p<0.001). A total of 6 patients with revision surgeries have been reported within the follow up period. It was not possible to correlate clinical features like lesion size, surgical approach, and bone marrow stimulation technique to the reported outcome. Surgical treatment of OCL via the AMIC procedure provided significant improvement in the functional outcome and pain scores when compared to the pre-operative values. Improvements were observed up to 5years post-operatively.

Recent studies highlighting mesenchymal stem cell (MSC) epigenetic memory suggest that a different differentiation medium may be required depending on the tissue of origin. As synovial-derived stem cells (SDSCs) attract interest we aimed to investigate the influence of TGF-β1, BMP-2 and dexamethasone on SDSC chondrogenesis in vitro. We demonstrate that dexamethasone-free medium led to enhanced chondrogenic differentiation at both the mRNA and matrix level. The greatest COL2A1/COL10A1 ratio was detected in cells exposed to a combination medium containing 10 ng/mL BMP-2 and 1 ng/mL TGF-β1 in the absence of dexamethasone, and this was reflected in the total amount of glycosaminoglycans produced. In summary, dexamethasone-free medium containing BMP-2 and TGF-β1 may be the most suitable when using SDSCs for cartilage tissue regeneration.

Although minimally invasive posterior spine implant systems have been introduced, clinical studies reported on reduced quality of spinal column realignment due to correction loss. The aim of this study was to compare biomechanically two minimally invasive spine stabilization systems versus the Universal Spine Stabilization system (USS). Three groups with 5 specimens each and 2 foam bars per specimen were instrumented with USS (Group 1) or a minimally invasive posterior spine stabilization system with either polyaxial (Group 2) or monoaxial (Group 3) screws. Mechanical testing was performed under quasi-static ramp loading in axial compression and torsion, followed by destructive cyclic loading run under axial compression at constant amplitude and then with progressively increasing amplitude until construct failure. Bending construct stiffness, torsional stiffness and cycles to failure were investigated. Initial bending stiffness was highest in Group 3, followed by Group 2 and Group 1, without any significant differences between the groups. A significant increase in bending stiffness after 20’000 cycles was observed in Group 1 (p = 0.002) and Group 2 (p = 0.001), but not in Group 3, though the secondary bending stiffness showed no significant differences between the groups. Initial and secondary torsional stiffness was highest in Group 1, followed by Group 3 and Group 2, with significant differences between all groups (p ≤ 0.047). A significant increase in initial torsional stiffness after 20’000 cycles was observed in Group 2 (p = 0.017) and 3 (p = 0.013), but not in Group 1. The highest number of cycles to failure was detected in Group 1, followed by Group 3 and Group 2. This parameter was significantly different between Group 1 and Group 2 (p = 0.001), between Group 2 and Group 3 (p = 0.002), but not between Group 1 and Group 3. These findings quantify the correction loss for minimally invasive spine implant systems and imply that unstable spine fractures might benefit from stabilization with conventional implants like the USS.