Human skin fibroblasts (HSFs) approximate the multidirectional differentiation potential of mesenchymal stem cells, so they are often used in differentiation, cell cultures, and injury repair. They are an important seed source in the field of bone tissue engineering. However, there are a few studies describing the mechanism of osteogenic differentiation of HSFs. Here, osteogenic induction medium was used to induce fibroblasts to differentiate into osteoblasts, and the role of the mechanical sensitive element PDLIM5 in microfilament-mediated osteogenic differentiation of human fibroblasts was evaluated. The depolymerization of microfilaments inhibited the expression of osteogenesis-related proteins and alkaline phosphatase activity of HSFs, while the polymerization of microfilaments enhanced the osteogenic differentiation of HSFs. The evaluation of potential protein molecules affecting changes in microfilaments showed that during the osteogenic differentiation of HSFs, the expression of PDLIM5 increased with increasing induction time, and decreased under the state of microfilament depolymerization. Lentivirus-mediated PDLIM5 knockdown by shRNA weakened the osteogenic differentiation ability of HSFs and inhibited the expression and morphological changes of microfilament protein. The inhibitory effect of knocking down PDLIM5 on HSF osteogenic differentiation was reversed by a microfilament stabilizer. Taken together, these data suggest that PDLIM5 can mediate the osteogenic differentiation of fibroblasts by affecting the formation and polymerization of microfilaments.

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In the interests of more flexible and less stiff bridge constructs to stimulate bone healing, the technique of far cortical locking has been designed to improve locked plating constructs in terms of stress concentration, stress shielding, and inhibition of issues around fracture healing. However, far cortical locking screws currently lack objective designs and anti-fatigue designs. This study investigates an optimization algorithm to form a special locking screw composed of various metals, which can theoretically achieve the maintenance of the excellent mechanical properties of far cortical locking constructs in terms of fracture internal fixation, while maintaining the biomechanical safety and fatigue resistance of the structure. The numerical results of our study indicate that the maximum von Mises stress of the optimized construct is less than the allowable stress of the material under each working condition while still achieving sufficient parallel interfragmentary motion. Numerical analysis of high cycle fatigue indicates that the optimized construct increases the safety factor to five. A high cycle fatigue test and defect analysis indicates that the sandwich locking constructs have better fatigue resistance. We conclude that the sandwich locking construct theoretically maintains its biomechanical safety and fatigue resistance while also maintaining excellent mechanical properties for fracture internal fixation.

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