Ready-to-use injectable calcium phosphate bone cement paste as drug carrier.

Current developments in calcium phosphate cement (CPC) technology concern the use of ready-to-use injectable cement pastes by dispersing the cement powder in a water-miscible solvent, such that, after injection into the physiological environment, setting of cements occurs by diffusion of water into the cement paste. It has also been demonstrated recently that the combination of a water-immiscible carrier liquid combined with suitable surfactants facilitates a discontinuous liquid exchange in CPC, enabling the cement setting reaction to take place. This paper reports on the use of these novel cement paste formulations as a controlled release system of antibiotics (gentamicin, vancomycin). Cement pastes were applied either as a one-component material, in which the solid drugs were physically dispersed, or as a two-component system, where the drugs were dissolved in an aqueous phase that was homogeneously mixed with the cement paste using a static mixing device during injection. Drug release profiles of both antibiotics from pre-mixed one- and two-component cements were characterized by an initial burst release of ∼7-28%, followed by a typical square root of time release kinetic for vancomycin. Gentamicin release rates also decreased during the first days of the release study, but after ∼1 week, the release rates were more or less constant over a period of several weeks. This anomalous release kinetic was attributed to participation of the sulfate counter ion in the cement setting reaction altering the drug solubility. The drug-loaded cement pastes showed high antimicrobial potency against Staphylococcus aureus in an agar diffusion test regime, while other cement properties such as mechanical performance or phase composition after setting were only marginally affected.

Dual setting α-tricalcium phosphate cements.

An extension of the application of calcium phosphate cements (CPC) to load-bearing defects, e.g. in vertebroplasty, would require less brittle cements with an increased fracture toughness. Here we report the modification of CPC made of alpha-tricalcium phosphate (α-TCP) with 2-hydroxyethylmethacrylate (HEMA), which is polymerised during setting to obtain a mechanically stable polymer-ceramic composite with interpenetrating organic and inorganic networks. The cement liquid was modified by the addition of 30-70 % HEMA and ammoniumpersulfate/tetramethylethylendiamine as initiator. Modification of α-TCP cement paste with HEMA decreased the setting time from 14 min to 3-8 min depending on the initiator concentration. The 4-point bending strength was increased from 9 MPa to more than 14 MPa when using 50 % HEMA, while the bending modulus decreased from 18 GPa to approx. 4 GPa. The addition of ≥50 % HEMA reduced the brittle fracture behaviour of the cements and resulted in an increase of the work of fracture by more than an order of magnitude. X-ray diffraction analyses revealed that the degree of transformation of α-TCP to calcium deficient hydroxyapatite was lower for polymer modified cements (82 % for polymer free cement and 55 % for 70 % HEMA) after 24 h setting, while the polymerisation of HEMA in the cement liquid was quantitative according to FT-IR spectroscopy. This work demonstrated the feasibility of producing fracture resistant dual-setting calcium phosphate cements by adding water soluble polymerisable monomers to the liquid cement phase, which may be suitable for an application in load-bearing bone defects.