Preparation and characterization of novel PMMA bone cement containing 3,4-dichloro-5-hydroxyfuran-2(5 H)-one

Abstract

Introduction: to address the issue of burst drug release in antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC), this study involved preparation of novel PMMA bone cement and determination of its antibacterial activity, biocompatibility, compressive properties, maximum temperature, and setting time. Methods: a novel acrylic monomer, which contains the 3,4-dichloro-5-hydroxyfuran-2(5H)-one (DHF), was synthesized and utilized to develop non-leaching antibacterial PMMA bone cement (NLBC), designated as DHF-methacrylic acid (DHF-MAA) bone cement. In the preparation of this bone cement, DHF-MAA served as a key component of the liquid phase. Its antibacterial activity was determined using a surface antibacterial assay. The biocompatibility of the cement was evaluated through a rabbit-suspended erythrocyte hemolysis test, assessment of the relative proliferation rate of mouse embryonic osteoblast precursor cells (MC3T3-E1) using the CCK-8 method, and an acute toxicity test in mice. The assessment of compressive properties includes both compressive strength and compressive modulus before and after aging. Results: DHF-MAA bone cement exhibited antibacterial activity, excellent biocompatibility, and acceptable compressive properties; in particular, the 10% DHF-MAA bone cement, achieved 100% antibacterial activity, excellent biocompatibility, and a compressive strength that met the compressive value, as stated in ISO 5833. Conclusions: in this study, novel antibacterial non-leaching DHF-MAA bone cement was synthesized and evaluated for its antibacterial activity, biocompatibility, and compressive properties. In particular, the 10% DHF-MAA bone cement exhibited excellent antibacterial activity, biocompatibility, and acceptable compressive properties. As such, this cement formulation warrants further characterization with a view to using it to anchor cemented arthroplasties.

Fig. 1. Synthetic route of DHF-MAA.

Fig. 2. FT-IR spectra of the powder of PMMA cement and three DHF-MAA bone cement formulations.

Fig. 3. (A) Petri dishes containing extracts from specimens of PMMA cement and four DHF-MAA bone cement formulations; (B) bar charts of the antibacterial indexes of DHF-MAA bone cement formulations. (* indicates p < 0.05 compared to the 10% DHF-MAA bone cement group, ** indicates p < 0.001 compared to the 10% DHF-MAA bone cement group).

Fig. 4. (A) Visual inspection of hemolysis test results for the PMMA cement and four DHF-MAA bone cement formulations; negative control group (−); and positive control group (+); (B) bar chart of hemolysis indexes for the PMMA cement group and four DHF-MAA bone cement formulations.

Fig. 5. Bar charts of RGR for the control group (complete medium), PMMA cement group and four DHF-MAA bone cement formulations day 1, day 3, and day 5. (* indicates p < 0.05 compared to the control group, and ^ indicates p < 0.05 when compared to the same concentration on day 1).

Fig. 6. Compressive strength (A) and compressive modulus (B) of PMMA cement and three four DHF-MAA bone cement formulations. (* indicates p < 0.05 compared to the PMMA group, ^ indicates p < 0.05 when compared to the same group before aging.)

Fig. 7. Slices of liver (A) and kidney (B) of mice from the normal saline (NS) group, PMMA cement group, and the DHF-MAA bone cement groups.