Quantifying effects of interactions between polyacrylic acid and chlorhexidine in dicalcium phosphate–forming cements

The aim of this study was to assess how varying the ratio of aqueous 0.8 M citric acid : 6 M polyacrylic acid (PAA) (3 : 0, 1 or 3 by weight) affected setting chemistry, mechanical properties and chlorhexidine di-acetate Biaxial flexural strength and modulus were determined after 24 hours setting plus 24 hours in water at 37 C and analysed using Weibull type equations. CHX release from 1 mm thick set discs was assessed over 4 weeks using UV spectroscopy. FTIR demonstrated that CHX interaction with citric acid inhibited formation of the reactive citrate/dicalcium phosphate intermediate complex that enables delay before snap set. High CHX additionally increased strength variability. Upon partial citric acid substitution with higher levels of PAA, delay before cement set was maintained. Monetite instead of brushite, however, was formed in conjuction with more stable polyacrylate complexes. These formulations had much improved strength but also greater modulus. CHX addition and interaction with PAA encouraged greater brushite instead of monetite formation. These complex interactions enabled formulations with high drug and PAA to have improved strength without increase in modulus. They also had low strength variability and better (slower) controlled release of drug. These properties are beneficial for cement use in a range of orthopaedic and dental applications

Development of microspheres for biomedical applications: a review

An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented

Doping of a high calcium oxide metaphosphate glass with titanium dioxide

This study investigates the effect of doping a high calcium oxide containing metaphosphate glass series (CaO)(40)(Na2O)(10)(P2O5)(50) with TiO2 (1, 3, and 5 mol%). TiO2 incorporation increased the density and glass transition temperature while reduced the degradation rate (5 mol% in particular) by twofold compared with (CaO)30 system reported previously. This has been confirmed by ion release and the minimal pH changes. TiP2O7, NaCa(PO3)(3) and CaP2O6 phases were detected for all TiO2-containing ceramics. XPS showed that the surface is composed of Ca, h, and Ti. Ti was recognized mainly as TiO2, but its total amount was lower than theoretical values. P-31 magic angle spinning (MAS) NMR showed a downfield shift of the P-31 lineshape with increasing TiO2, interpreted as an effect of the titanium cation rather than an increase in the phosphate network connectivity. FTIR showed that incorporation of TiO2 increased the strength of the phosphate chains, and the O/P ratio while introducing more Q(1) units into the structure at the expense of the Q(2) units. There were no differences, however, in surface topography roughness and free energies between these glasses. These results suggested that TiO2 and CaO were acting synergistically in producing glasses with controllable bulk and structural propertie

Identification of phases in partially crystallised Ti-, Sr- and Zn-containing sodium calcium phosphates by two-dimensional NMR

P-31 and Na-23 one-dimensional MAS NMR, as well as two-dimensional P-31 refocused INADEQUATE and Na-23 multiple quantum (MQ) MAS, experiments have been used in combination with powder XRD to identify various phases present in three metal-containing sodium calcium phosphate ceramics of interest as potential biomaterials. Each sample is shown to consist of multiple phases (at least seven in the case of the Zn-containing sample), several of which were identified by NMR, but not by XRD. Solid-state NMR is thus demonstrated to be an important characterisation tool in studying multi-phase phosphate ceramics, especially those containing a mixture of crystalline and amorphous components. (C) 2008 Elsevier B.V. All rights reserved

Processing, characterisation, and biocompatibility of zinc modified metaphosphate based glasses for biomedical applications

Bulk and structural properties of zinc oxide (0 up to 20 mol%) containing phosphate glasses, developed for biomedical applications, were investigated throughout this study using differential thermal analysis (DTA), differential scanning calorimetry, X-ray powder diffraction and P-31 and Na-23 MAS NMR. Surface wettability and MG63 viability were also considered for surface characterisation of these glasses. The results indicated that incorporation of zinc oxide as a dopant into phosphate glasses produced a significant increase in density; however, the thermal properties presented in glass transition, and melting temperatures were reduced. NaZn(PO3)(3) was detected in the X-Ray Powder Diffraction Analysis (XRD) trace of zinc containing glasses, and the proportion of this phase increased with increasing zinc oxide content. NaCa(PO3)(3) as a second main phase and CaP2O6 in minor amounts were also detected. The P-31 and Na-23 MAS NMR results suggested that the relative abundances of the Q(1) and Q(2) phosphorus sites, and the local sodium environment were unaffected as CaO was replaced by ZnO in this system. The replacement of CaO with ZnO did seem to have the effect of increasing the local disorder of the Q(2) metaphosphate chains, but less so for the Q(1) chain-terminating sites which were already relatively disordered due to the proximity of modifying cations. Glasses with zinc oxide less than 5 mol% showed higher surface wettability, while those with 5 up to 20 mol% showed comparable wettability as zinc oxide free glasses. Regardless of the high hydrophilicity and surface reactivity of these zinc oxide containing glasses, they had lower biocompatibility, in particular 10-20 mol% ZnO, compared to both zinc free glasses and Thermanox (R). This may be associated with the release of significant amount of Zn2+ enough to be toxic to MG63

Identification of phases in partially crystallised Ti-, Sr- and Zn-containing sodium calcium phosphates by two-dimensional NMR

P-31 and Na-23 one-dimensional MAS NMR, as well as two-dimensional P-31 refocused INADEQUATE and Na-23 multiple quantum (MQ) MAS, experiments have been used in combination with powder XRD to identify various phases present in three metal-containing sodium calcium phosphate ceramics of interest as potential biomaterials. Each sample is shown to consist of multiple phases (at least seven in the case of the Zn-containing sample), several of which were identified by NMR, but not by XRD. Solid-state NMR is thus demonstrated to be an important characterisation tool in studying multi-phase phosphate ceramics, especially those containing a mixture of crystalline and amorphous components. (C) 2008 Elsevier B.V. All rights reserved

Control of Surface Free Energy in Titanium Doped Phosphate Based Glasses by Co-Doping With Zinc

To significantly improve the biocompatibility of titanium doped phosphate based glasses, codoping with zinc has been attempted. This study investigated the effect of doping a quaternary 15Na(2)O:30CaO:5TiO(2):50P(2)O(5) glass with zinc oxide (1, 3, and 5 mol %) on bulk, structural, surface, and biological properties; the results were compared with glasses free from ZnO and/or TiO2. ZnO as adjunct to TiO2 was effective in changing density, interchain bond forces, degradation behavior, and ions released from the degrading glasses. Incorporation of both TiO2 and ZnO in T5Z1, T5Z3, and T5Z5 glasses reduced the level of Zn2+ release by two to three orders of magnitude compared with glasses containing ZnO only (Z5). P-31 NMR results for T5Z1, T5Z3, and T5Z5 glasses showed the presence of Q(3) species suggesting that the TiO2 is acting as a network former, and the phosphate network becomes slightly more connected with increasing ZnO incorporation. Regardless of their relative lower hydrophilicity and surface reactivity compared with the control glass free from TiO2 and ZnO (T0Z0), these glasses have significantly higher surface reactivity compared with Thermanox (R). This has been also reflected in the maintenance of >98% viable Osteoblasts, proliferation rate, and expression level of osteoblastic marker genes in a comparable manner to Thermanox (R) and T5 glasses, particularly T5Z1 and T5Z3 glasses. However, T0Z0 and Z5 glasses showed significantly reduced viability compared to Thermanox (R). Therefore, it can be concluded that ZnO doped titanium phosphate glasses, T5Z1 and T5Z3 in particular, can be promising substrates for bone tissue engineering applications. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 89B: 392-407, 200

Quantifying effects of interactions between polyacrylic acid and chlorhexidine in dicalcium phosphate-forming cements

The aim of this study was to assess how varying the ratio of aqueous 0.8 M citric acid[thin space (1/6-em)]:[thin space (1/6-em)]6 M polyacrylic acid (PAA) (3[thin space (1/6-em)]:[thin space (1/6-em)]0, 1 or 3 by weight) affected setting chemistry, mechanical properties and chlorhexidine di-acetate (CHX) release of dicalcium phosphate – forming bone cements. Cement powder included β-tricalcium phosphate (β-TCP)[thin space (1/6-em)]:[thin space (1/6-em)]monocalcium phosphate monohydrate (MCPM)[thin space (1/6-em)]:[thin space (1/6-em)]CHX at 1[thin space (1/6-em)]:[thin space (1/6-em)]1[thin space (1/6-em)]:[thin space (1/6-em)](0, 0.08 or 0.16) molar ratio. Powder to liquid ratio was fixed at 3[thin space (1/6-em)]:[thin space (1/6-em)]1 by weight. Chemical setting kinetics, reactive intermediate formation and final product homogeneity were assessed by ATR FTIR and Raman mapping. Biaxial flexural strength and modulus were determined after 24 hours setting plus 24 hours in water at 37 °C and analysed using Weibull type equations. CHX release from 1 mm thick set discs was assessed over 4 weeks using UV spectroscopy. FTIR demonstrated that CHX interaction with citric acid inhibited formation of the reactive citrate/dicalcium phosphate intermediate complex that enables delay before snap set. High CHX additionally increased strength variability. Upon partial citric acid substitution with higher levels of PAA, delay before cement set was maintained. Monetite instead of brushite, however, was formed in conjuction with more stable polyacrylate complexes. These formulations had much improved strength but also greater modulus. CHX addition and interaction with PAA encouraged greater brushite instead of monetite formation. These complex interactions enabled formulations with high drug and PAA to have improved strength without increase in modulus. They also had low strength variability and better (slower) controlled release of drug. These properties are beneficial for cement use in a range of orthopaedic and dental applications