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Biological Compatibility Profile on Biomaterials for Bone Regeneration
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Novel composite bone cement modulates inflammatory response in vitro.

Kangning Hao1, Jie Hu2, Jiangyong Wang1

  • 1Department of Orthopaedic Surgery, The Third Hospital of Shijiazhuang City, No. 15, TiYu South Street, Shijiazhuang City, Hebei Province, People's Republic of China.

Scientific Reports
|March 15, 2025
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Enoxaparin sodium polymethylmethacrylate (ES-PMMA) bone cement exhibits anti-inflammatory properties by reducing pro-inflammatory factors like IL-6 and promoting IL-10. This bone cement also aids M2 macrophage polarization and decreases endothelial cell apoptosis, suggesting potential surgical applications.

Keywords:
Co-culture systemInflammationIntercellular cell adhesion moleculeInterleukin-10Interleukin-6Macrophage polarisationTumour necrosis factor-α

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Area of Science:

  • Biomaterials Science
  • Immunology
  • Cell Biology

Background:

  • Inflammation is a critical factor in the success of bone cement applications.
  • Understanding the interaction between bone cement, immune cells, and endothelial cells is crucial for improving clinical outcomes.
  • Polymethylmethacrylate (PMMA) bone cement is widely used, but its inflammatory effects require investigation.

Purpose of the Study:

  • To evaluate the anti-inflammatory properties of enoxaparin sodium-modified PMMA (ES-PMMA) bone cement.
  • To investigate the impact of ES-PMMA on macrophage polarization and endothelial cell apoptosis in an inflammatory model.
  • To assess the modulation of key inflammatory factors, Interleukin-6 (IL-6) and Interleukin-10 (IL-10), by ES-PMMA.

Main Methods:

  • An indirect co-culture system of endothelial cells and macrophages was established using lipopolysaccharide (LPS) to induce inflammation.
  • Flow cytometry was used to analyze macrophage polarization (M1/M2 markers CD86/CD206) and endothelial cell apoptosis.
  • ELISA, Western blotting, and immunofluorescence were employed to measure the expression levels of IL-6, Tumor Necrosis Factor-alpha (TNF-α), Intercellular Cell Adhesion Molecule (ICAM), and IL-10.

Main Results:

  • ES-PMMA significantly reduced the expression of pro-inflammatory markers (IL-6, TNF-α, ICAM) and increased anti-inflammatory IL-10 compared to LPS-induced controls.
  • ES-PMMA promoted M2 macrophage polarization (increased CD206, decreased CD86) and significantly reduced endothelial cell apoptosis.
  • These effects were more pronounced with ES-PMMA compared to unmodified PMMA in the presence of LPS.

Conclusions:

  • ES-PMMA bone cement demonstrates significant anti-inflammatory effects by modulating cytokine profiles (reducing IL-6, increasing IL-10).
  • ES-PMMA facilitates a shift towards a pro-resolving M2 macrophage phenotype and protects endothelial cells from apoptosis.
  • These findings highlight the potential of ES-PMMA bone cement to improve the local inflammatory environment in cement-related surgical applications.