Composite Bone Cements with Enhanced Drug Elution

Abstract

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC).

Keywords: ALBC; NFC; PMMA; antibiotic release; bone cement; nanocellulose; vancomycin.

Figure 1

Temperature profiles and setting times of ALBC and c-ALBC samples. The corresponding setting times (denoted by double side arrows) and maximum temperatures reached during polymerization of the sample in the cubic form (1 cm × 1 cm × 1 cm) are presented in the Figure; *—the presented settings times are given from the start of temperature registration.

Figure 2

MMA leaching after 10 min extraction in 4 mL of n-hexane. The corresponding released MMA quantities (in regard to the total weight of sample) are presented in the figure.

Figure 3

Vancomycin elution from ALBC and c-ALBC over 269 h. The insert: vancomycin elution during first 10 h. For visual convenience, the data are presented in scatter-line format.

Figure 4

Microhardness tests of the samples of the bone cement, ALBC, and c-ALBC. The corresponding values of Martens hardness (HM) are indicated in the figure.

Figure 5

SEM micrographs of bone cement, ALBC, and c-ALBC. The orange rectangular indicates the acquisition zone of the micrographs of the higher magnification; the red and green arrows indicate the fillers and the antibiotic microgranules, respectively.