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. 2024 May 28:12:1414005.
doi: 10.3389/fbioe.2024.1414005. eCollection 2024.

Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds

Rui Guo #  1   2 , Yu-Chen Kan #  1   2 , Yang Xu #  3 , Lu-Yang Han  1 , Wen-Han Bu  1 , Long-Xu Han  1 , Yin-Yu Qi  1 , Jian-Jun Chu  1   2
Affiliations

Preparation and efficacy of antibacterial methacrylate monomer-based polymethyl methacrylate bone cement containing N-halamine compounds

Rui Guo et al. Front Bioeng Biotechnol. .

Abstract

Introduction: Our objective in this study was to prepare a novel type of polymethyl methacrylate (PMMA) bone cement, analyze its material properties, and evaluate its safety and antibacterial efficacy.

Methods: A halamine compound methacrylate antibacterial PMMA bone cement containing an N-Cl bond structure was formulated, and its material characterization was determined with Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR. The antibacterial properties of the material were studied using contact bacteriostasis and releasing-type bacteriostasis experiments. Finally, in vitro and in vivo biocompatibility experiments were performed to analyze the toxic effects of the material on mice and embryonic osteoblast precursor cells (MC3T3-E1).

Results: Incorporation of the antibacterial methacrylate monomer with the N-halamine compound in the new antibacterial PMMA bone cement significantly increased its contact and releasing-type bacteriostatic performance against Staphylococcus aureus. Notably, at 20% and 25% additions of N-halamine compound, the contact and releasing-type bacteriostasis rates of bone cement samples reached 100% (p < 0.001). Furthermore, the new antibacterial bone cement containing 5%, 10%, and 15% N-halamine compounds showed good biocompatibility in vitro and in vivo.

Conclusion: In this study, we found that the novel antibacterial PMMA bone cement with N-halamine compound methacrylate demonstrated good contact and releasing-type bacteriostatic properties against S. aureus. In particular, bone cement containing a 15% N-halamine monomer exhibited strong antibacterial properties and good in vitro and in vivo biocompatibility.

Keywords: N-halamine compound; Staphylococcus aureus; antibacterial cement; bone cement modification; infection; polymethyl methacrylate.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Synthesis of a methacrylate antimicrobial monomer with halamine containing an N-Cl bond structure.
FIGURE 2
FIGURE 2
(Continued). (A) Infrared spectra of the PMMA bone cement and bone cements with 5%, 15%, and 25% N-halamine compound monomers. (B) 1H-NMR spectra of methacrylate monomer containing N-halamine compound (ppm, CDCl3).
FIGURE 3
FIGURE 3
Detection of contact antibacterial performance. (A) The number of bacteriostatic colonies of contact bacteriostasis (compared with the PMMA group, * indicates p < 0.05, ** indicates p < 0.001). (B) Contact bacteriostasis rate. (C–G) show the colonies of Staphylococcus aureus in the dishes of PMMA bone cement and bone cements with 10%, 15%, 20%, and 25% N-halamine compound monomers, respectively. In the dish shown in f, the activity of Staphylococcus aureus is reduced. No Staphylococcus aureus colonies are formed in the dish shown in (G).
FIGURE 4
FIGURE 4
Detection of releasing-type antibacterial performance. (A) The number of bacteriostatic colonies of releasing-type bacteriostasis (compared with the PMMA group, * indicates p < 0.05, ** indicates p < 0.001). (B) Releasing-type bacteriostasis rate. (C–G) show the colonies of Staphylococcus aureus in the dishes of PMMA bone cement and bone cements with 5%, 10%, 15%, and 20% N-halamine compound monomers, respectively. In the dish shown in f, the activity of Staphylococcus aureus is reduced. No Staphylococcus aureus colonies are formed in the dish shown in (G).
FIGURE 5
FIGURE 5
In vitro cell proliferation and toxicity experiments. (A–G) show the morphology of MC3T3-E1 cells in the control group, PMMA bone cement group, and bone cement groups with 5%, 10%, 15%, 20%, and 25% N-halamine compound monomers, respectively, on day 5 as observed under the microscope. (H,I) show the OD values and relative proliferation rates of cells in each group at different time points (when the concentration of N-halamine compound monomer is 15%, the OD values of cells on days 3 and 5 are compared with those on day 1, * indicates p < 0.05; the bone cement with 20% and 25% N-halamine compound monomer groups are compared with the blank control group, ** indicates p < 0.001).
FIGURE 6
FIGURE 6
Histological staining images of mice livers on day 3 after the intraperitoneal injection, as observed under a light microscope. (A–G) show histological staining images of mice livers on day 3 after the injection in the control group, PMMA bone cement group, and bone cement groups with 5%, 10%, 15%, 20%, and 25% N-halamine compound monomers (hematoxylin-eosin staining).
FIGURE 7
FIGURE 7
Histological staining images of mice kidneys on day 3 after the intraperitoneal injection, as observed under a light microscope. (A–G) show the histological staining images of mice kidneys on day 3 after the intraperitoneal injection in the control group, PMMA bone cement group, and bone cement groups with 5%, 10%, 15%, 20%, and 25% N-halamine compound monomers (hematoxylin-eosin staining).
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