The antibiotics supplemented bone cement improved the masquelet's induced membrane in a rat femur critical size defect model

Injury. 2023 Feb;54(2):329-338. doi: 10.1016/j.injury.2022.10.027. Epub 2022 Oct 27.

Abstract

Background: Masquelet technique is a two-stage surgical procedure used in the treatment of critical-size bone defects (CSD). Adding antibiotics to polymethylmethacrylate (PMMA) is still questionable to create higher quality induced membrane (IM). The aim of the study was to evaluate the effects of three antibiotic-supplemented cement, fusidic acid, teicoplanin, and gentamicin, on osteogenesis and IM progression applied to rat femur CSD model by comparing histopathological, biochemical, and immunohistochemical findings.

Methods: Twenty-eight male rats were divided into four groups control, gentamicin (G), teicoplanin (T), and fusidic acid (FA). A 10 mm CSD was created in rat femurs. In the postoperative 4th week, intracardiac blood samples were collected for biochemical analysis of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) levels. IMs obtained in secondary operation were fixed and prepared for histopathological scoring of membrane progression and immunohistochemical evaluation of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) expressions.

Results: Levels of BALP and OC in serum didn't change among groups significantly while serum TNF-α levels significantly decreased in all antibiotic groups compared to the control group (P = 0.017). Histological scores of groups FA and T were significantly higher than those of groups Control and G (P = 0.0007). IMs of groups T and FA showed good progression while those of groups Control and G were also moderately progressed. A significant increase in TGF-β expression was observed in group G and FA (P = 0.001) while a significant increase in the expression of VEGF was observed in groups G and T compared to the control group (P = 0.036).

Conclusions: The bone cement impregnated with thermostable and safe antibiotics, gentamicin, fusidic acid, and teicoplanin can increase osteogenesis and support IM progression by increasing the expressions of TGF-β and VEGF. Anabolic effects of induced membranes used in the treatment of critical-size bone defects can be enhanced by antibiotic-supplemented PMMAs applied by altering the original technique.

Keywords: Cement; Critical size defect; Foreign body reaction; Fusidic acid; Gentamicin; Induced membrane; Masquelet technique; Polymethylmethacrylate; Teicoplanin; antibiotic.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / pharmacology
  • Bone Cements* / pharmacology
  • Femur / surgery
  • Fusidic Acid
  • Gentamicins / pharmacology
  • Male
  • Rats
  • Teicoplanin
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A

Substances

  • Anti-Bacterial Agents
  • Bone Cements
  • Vascular Endothelial Growth Factor A
  • Fusidic Acid
  • Teicoplanin
  • Tumor Necrosis Factor-alpha
  • Gentamicins
  • Transforming Growth Factor beta