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When aiming at cell‐based therapies in osteoarthritis (OA), proinflammatory conditions mediated by cytokines such as IL‐1β need to be considered. In recent studies, the phytoalexin resveratrol (RSV) has exhibited potent anti‐inflammatory properties. However, long‐term effects on 3D cartilaginous constructs under inflammatory conditions with regard to tissue quality, especially extracellular matrix (ECM) composition, have remained unexplored. Therefore, we employed long‐term model cultures for cell‐based therapies in an in vitro OA environment and evaluated effects of RSV. Pellet constructs made from expanded porcine articular chondrocytes were cultured with either IL‐1β (1–10 ng/ml) or RSV (50 μM) alone, or a cotreatment with both agents. Treatments were applied for 14 days, either directly after pellet formation or after a preculture period of 7 days. Culture with IL‐1β (10 ng/ml) decreased pellet size and DNA amount and severely compromised glycosaminoglycan (GAG) and collagen content. Cotreatment with RSV distinctly counteracted the proinflammatory catabolism and led to partial rescue of the ECM composition in both culture systems, with especially strong effects on GAG. Marked MMP13 expression was detected in IL‐1β‐treated pellets, but none upon RSV cotreatment. Expression of collagen type I was increased upon IL‐1β treatment and still observed when adding RSV, whereas collagen type X, indicating hypertrophy, was detected exclusively in pellets treated with RSV alone. In conclusion, RSV can counteract IL‐1β‐mediated degradation and distinctly improve cartilaginous ECM deposition in 3D long‐term inflammatory cultures. Nevertheless, potential hypertrophic effects should be taken into account when considering RSV as cotreatment for articular cartilage repair techniques.
Background
Tibial head depression fractures demand a high level of fracture stabilization to prevent a secondary loss of reduction after surgery. Elderly individuals are at an increased risk of developing these fractures, and biomechanical investigations of the fractures are rare. Therefore, the aim of this study was to systematically analyze different types of osteosyntheses in combination with two commonly used bone substitutes.
Methods
Lateral tibial head depression fractures were created in synthetic bones. After reduction, the fractures were stabilized with eight different treatment options of osteosynthesis alone or in combination with a bone substitute. Two screws, 4 screws and a lateral buttress plate were investigated. As a bone substitute, two common clinically used calcium phosphate cements, Norian® Drillable and ChronOS™ Inject, were applied. Displacement of the articular fracture fragment (mm) during cyclic loading, stiffness (N/mm) and maximum load (N) in Load-to-Failure tests were measured.
Results
The three different osteosyntheses (Group 1: 2 screws, group 2: 4 screws, group 3: plate) alone revealed a significantly higher displacement compared to the control group (Group 7: ChronOS™ Inject only) (Group 1, 7 [p < 0.01]; group 2, 7 [p = 0.04]; group 3, 7 [p < 0.01]). However, the osteosyntheses in combination with bone substitute exhibited no differences in displacement compared to the control group. The buttress plate demonstrated a higher normalized maximum load than the 2 and 4 screw osteosynthesis. Comparing the two different bone substitutes to each other, ChronOS™ inject had a significantly higher stiffness and lower displacement than Norian® Drillable.
Conclusions
The highest biomechanical stability under maximal loading was provided by a buttress plate osteosynthesis. A bone substitute, such as the biomechanically favorable ChronOS™ Inject, is essential to reduce the displacement under lower loading.