Preparation and Characterization of Injectable Brushite Filled-Poly (Methyl Methacrylate) Bone Cement

Abstract

Powder-liquid poly (methyl methacrylate) (PMMA) bone cements are widely utilized for augmentation of bone fractures and fixation of orthopedic implants. These cements typically have an abundance of beneficial qualities, however their lack of bioactivity allows for continued development. To enhance osseointegration and bioactivity, calcium phosphate cements prepared with hydroxyapatite, brushite or tricalcium phosphates have been introduced with rather unsuccessful results due to increased cement viscosity, poor handling and reduced mechanical performance. This has limited the use of such cements in applications requiring delivery through small cannulas and in load bearing. The goal of this study is to design an alternative cement system that can better accommodate calcium-phosphate additives while preserving cement rheological properties and performance. In the present work, a number of brushite-filled two-solution bone cements were prepared and characterized by studying their complex viscosity-versus-test frequency, extrusion stress, clumping tendency during injection through a syringe, extent of fill of a machined void in cortical bone analog specimens, and compressive strength. The addition of brushite into the two-solution cement formulations investigated did not affect the pseudoplastic behavior and handling properties of the materials as demonstrated by rheological experiments. Extrusion stress was observed to vary with brushite concentration with values lower or in the range of control PMMA-based cements. The materials were observed to completely fill pre-formed voids in bone analog specimens. Cement compressive strength was observed to decrease with increasing concentration of fillers; however, the materials exhibited high enough strength for consideration in load bearing applications. The results indicated that partially substituting the PMMA phase of the two-solution cement with brushite at a 40% by mass concentration provided the best combination of the properties investigated. This alternative material may find applications in systems requiring highly injectable and viscous cements such as in the treatment of spinal fractures and bone defects.

Keywords: Poly (methyl methacrylate) bone cement; calcium phosphate; complex viscosity; compressive strength; polymer composites; rheology.

Figure 1

The graphical representations of (a) the acquisition of the linear viscoelastic region and (b) the extrusion stress of the materials examined. The near-zero complex viscosity was correlated to the stress value at that point to yield extrusion stress as indicated in the graph (b) with dashed lines.

Figure 2

The extrusion force monitored over time for (A) composite bone substitute (CBS) 50 40% filled compositions demonstrating a lack of clumping evidenced by uniform stress required to extrude the material from its cartridge; and (B) CBS 50 50% filled compositions demonstrating clumping evidenced by the increased extrusion force in the first third of the experiment.

Figure 3

Flow and sealing effectiveness of the CBS 50 (40% filled) cement. The figure illustrates the material fully sealing a Sawbones^® defect of interest (2 mm × 10 mm) without leaving gaps along the interface using a rigid polyurethane foam model. The panels are arranged in order of increasing depth into the defect from left to right. No pressurization was necessary for the material to fill down toward the bottom of the defect. “SB” denotes Sawbones^®, and “C” denoted cement.

Figure 4

Complex viscosity of investigated materials over a range of angular frequencies (100–0.1 Hz). The shear-thinning effect of all cement compositions compared is demonstrated by the accentuated decrease in viscosity with increasing shear rate. (A) CBA materials vs. control showing no change in rheological characteristics among the formulations compared; (B) CBS 25 materials vs. control showing an increase in complex viscosity with an increase in filler concentration up to saturation. Note the curves for the 30% and 40% CBS 25 overlap; (C) CBS 50 materials vs. control showing a steady increase in complex viscosity with increasing concentration of filler in the material. It is interesting to note that although viscosity increased with these formulations, the materials’ pseudoplasticity also increased. Each of the formulations investigated other than the 50% filled CBS 50 resulted in significantly similar rheological characteristics in comparison to the control all-acrylic cement (p < 0.05).

Figure 5

Analysis of Variance (ANOVA) values of the rheological data presented in Figure 4. Vertical dotted lines indicate the level of statistical significance. Samples which fall outside of these margins (CBS 50 panel) are statistically different across their means.

Figure 6

Compressive strength graphs of the materials investigated. The incorporation of CaP into the samples decreased the compressive strength of the materials investigated. The incorporation of CaP into the cement matrix resulted in more porous materials with decreased mechanical stability.

Figure 7

Analysis of Variance (ANOVA) values of the mechanical strength data presented in Figure 6. Vertical dotted lines indicate the level of statistical significance. Samples which fall outside of these margins are statistically different across their means.