The coefficients of variation of the cellulose cement were significantly less than those of the traditional antibiotic cement (p = 0.0014), ie, 0.052 versus 0.108 for compression strength, 0.029 versus 0.074 for fracture toughness, 0.077 versus 0.146 for vancomycin release at Day 35, and 0.089 versus 0.154 for gentamicin release at Day 35. Thus, the data for the cellulose antibiotic cement were more consistent than those for the traditional cement. The fatigue-life data were not included in the analysis, because they did not fit normal distribution curves, as reported previously [13-15].
A major disadvantage of traditional antibiotic bone cements is that release of the antibiotics is limited [11, 12, 16, 21]. Although increasing the amount of antibiotic incorporated increases the level of its release [7, 13], 4 g or greater of antibiotic to 40 g of PMMA powder compromises the compression strength [7, 12], fracture toughness , and fatigue life [12, 13, 17] of the material. Therefore, we investigated whether incorporating bacterial cellulose would improve the mechanical strength of bone cement containing 5 g of antibiotics and increase antibiotic release.
We recognize that there are certain limitations to our study. First, we did not evaluate several important factors that may be correlated with the in vitro studies described here, such as the in vivo elution kinetics, in vivo mechanical behavior, and inhibition of bacterial proliferation and biofilm formation [12, 22]. Elucidation of these factors is crucial. Second, we cannot draw any conclusions regarding the effects of incorporating cellulose into bone cements in clinical practice. However, our data do suggest that incorporating cellulose into bone cement is advantageous and warrants further study. Third, the optimal loads of antibiotics and cellulose were not determined. These issues should be examined in future studies, with a focus on clinical applications, such as implant fixation and the control of resistant organisms.
The mechanical strength of antibiotic cement containing 5 g of antibiotic per 40 g PMMA powder was improved by incorporating cellulose. Although there is a lack of consensus regarding experimental designs when considering enhancement of the mechanical properties of bone cement , the use of antibiotics at dosages of 4 g or greater has resulted in reduced compression strength  and fatigue life , with values similar to those obtained for the traditional antibiotic cement in this study (Table 4). Our study showed that bone cement incorporating bacterial cellulose maintains its compression strength and fracture toughness even when loaded with 5 g of antibiotic. Although the fatigue life of the cellulose antibiotic cement tended to be shorter than that of plain cement, it was 4.5 times longer than that of traditional antibiotic cement. This unique property of cellulose antibiotic cement might permit loading with high levels of antibiotics (3.5 g or greater) [6, 23] in applications such as implant fixation, for which mechanical strength and longevity are essential [13, 22].
After incorporation of cellulose into bone cement, the cumulative release of antibiotics over 14 days was greater. PMMA-based cement is hydrophobic and impermeable to antibiotics , whereas cellulose is hydrophilic and antibiotic-permeable . Therefore, antibiotic release may be facilitated by gradual penetration of fluid through an interconnecting series of hydrophilic cellulose and antibiotic agglomerates. Absorbable materials such as dextran , poly ε-caprolactone , and lactose , have been used to increase antibiotic release from bone cement impregnated with low doses of antibiotics, resulting in release rates threefold to fourfold greater than those from traditional antibiotic cement: traditional cement versus dextran-loaded cement (91 μg/cm2 versus 323 μg/cm2) , versus poly ε-caprolactone (306 μg/cm2 versus 960 μg/cm2) , and versus lactose (460 μg/cm2 versus 2100 μg/cm2) . In the current study, using a high dose of antibiotics, cellulose incorporation increased antibiotic release by only 1.3-fold as compared with traditional cement. However, the cumulative release rates per unit of surface area of the cements that contained absorbable materials were similar or less than the corresponding values for antibiotic cement. There also has been concern that incorporating absorbable materials might compromise the mechanical properties of the cement. An antibiotic cement containing poly(ε-caprolactone) had only 50% of the compression strength and 35% of the tensile strength of a traditional antibiotic cement  (Table 5). Although additional studies are needed to compare release modulators under the same experimental conditions, our data suggest that incorporation of cellulose can increase antibiotic release from bone cement containing a high level of antibiotics while preserving its mechanical properties.
Unexpectedly, we found fewer flaws in the cellulose antibiotic cement than in the traditional antibiotic cement, in which the incidence of flaws was 23%, similar to the incidence in a previous study . These flaws might contribute to an initial burst of antibiotic release or to mechanical fragility [12, 21]. Even in the samples without flaws, the variability of the features examined was less pronounced in the cellulose antibiotic cement than in the traditional antibiotic cement. As antibiotic delivery systems used in clinical practice must be consistent, the lower frequency of flaws and smaller variance favors cellulose antibiotic cement over traditional antibiotic cement.
Compared with a traditional antibiotic cement with a high dose of antibiotics (5 g per 40 g cement powder), incorporating antibiotic-loaded cellulose prevented reductions in compression strength and fracture toughness, reduced adverse effects on fatigue life, and increased antibiotic release. Cements containing antibiotic-loaded cellulose may have applications in clinical situations that require a high level of antibiotic release and preservation of the mechanical properties of the bone cement.
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