Effective production of multifunctional magnetic-sensitive biomaterial by an extrusion-based additive manufacturing technique.

A calcium phosphate (CaP)-based scaffold used as synthetic bone grafts, which smartly combines precise dimensions, controlled porosity and therapeutic functions, presents benefits beyond those offered by conventional practices, although its fabrication is still a challenge. The sintering step normally required to improve the strength of the ceramic scaffolds precludes the addition of any biomolecules or functional particles before this stage. This study presents a proof of concept of multifunctional CaP-based scaffolds, fabricated by additive manufacturing from an innovative ink composition, with potential for bone regeneration, cancer treatment by local magnetic hyperthermia and drug delivery platforms. Highly loaded inks comprising iron-doped hydroxyapatite and ß-tricalcium phosphate powders suspended in a chitosan-based solution, in the presence of levofloxacin (LEV) as model drug and magnetic nanoparticles (MNP), were developed. The sintering step was removed from the production process, and the integrity of the printed scaffolds was assured by the polymerization capacity of the ink composite, using genipin as a crosslinking agent. The effects of MNP and LEV on the inks' rheological properties, as well as on the mechanical and structural behaviour of non-doped and iron-doped scaffolds, were evaluated. Magnetic and magneto-thermal response, drug delivery and biological performance, such as cell proliferation in the absence and presence of an applied magnetic field, were also assessed. The addition of a constant amount of MNP in the iron-doped and non-doped CaP-based inks enhances their magnetic response and induction heating, with these effects more pronounced for the iron-doped CaP-based ink. These results suggest a synergistic effect between the iron-doped CaP-based powders and the MNP due to ferro/ferrimagnetic interactions. Furthermore, the iron presence enhances human mesenchymal stem cell metabolic activity and proliferation.

Structure, conductivity and magnetism of orthorhombic and fluorite polymorphs in MoO3-Ln2O3 (Ln = Gd, Dy, Ho) systems.

Phase-pure orthorhombic compositions at a Ln/Mo ratio ∼ 5.2-5.7 (Ln = Gd, Dy, Ho) have been obtained for the first time by prolonged (40-160 h) heat treatment of mechanically activated 5Ln2O3 + 2MoO3 (Ln = Gd, Dy, Ho) oxide mixtures at 1200 °C. Although the starting Ln : Mo ratio was 5 : 1 (Ln10Mo2O21 (Ln = Dy, Ho)), it changed slightly in the final product due to the volatility of molybdenum oxide at 1200 °C (40-160 h) (ICP-MS analysis). Brief high-temperature firing (1600 °C, 3 h) of 5Ln2O3 + 2MoO3 (Ln = Gd, Dy, Ho) oxide mixtures leads to the formation of phase-pure fluorites with compositions close to Ln10Mo2O21 (Ln = Gd, Dy, Ho). Gd10Mo2O21 molybdate seems to undergo an order-disorder (orthorhombic-fluorite) phase transition in the range of 1200-1600 °C. For the first time, using the neutron diffraction method, it was shown that low-temperature phases with a Ln/Mo ratio ∼ 5.2-5.7 (Ln = Gd, Dy, Ho) have an orthorhombic structure rather than a tetragonal structure. Proton contribution to the total conductivity of Ln10Mo2O21 (Ln = Gd, Dy, Ho) fluorites and gadolinium and dysprosium orthorhombic phases in a wet atmosphere was observed for the first time. In both orthorhombic and fluorite phases, the total conductivity in wet air decreases with decreasing lanthanide ionic radii. In a wide temperature range, the compounds under study exhibit paramagnetic behaviour. However, the orthorhombic phases of Dy and Ho compounds reach the antiferromagnetic state at 2.4 K and 2.6 K, respectively.

Surface functionalization of cuttlefish bone-derived biphasic calcium phosphate scaffolds with polymeric coatings.

Cuttlefish bone (CB) has been explored as biomaterial in the bone tissue-engineering field due to its unique porous structure and capacity of the aragonite mineral to be hydrothermally converted into calcium phosphates (CaPs). In the present study, undoped and ion (Sr2+, Mg2+ and/or Zn2+) doped biphasic calcium phosphate (BCP) scaffolds were prepared by hydrothermal transformation (HT, 200 °C, 24 h) of CB. The obtained scaffolds were sintered and then coated with two commercial polymers, poly(ε-caprolactone) (PCL) or poly(DL-lactide) (PDLA), and with two synthesized ones, a poly(ester amide) (PEA) or a poly(ester urea) (PEU) in order to improve their compressive strength. The scaffolds were characterized by X-ray diffraction (XRD) coupled with structural Rietveld refinement, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The results demonstrate that CB could be entirely transformed into BCPs in the presence or absence of doping elements. The initial CB structure was preserved and the polymeric coatings did not jeopardize the interconnected porous structure. Furthermore, the polymeric coatings enhanced the compressive strength of the scaffolds. The in vitro bio-mineralization upon immersing the scaffolds into simulated body fluid (SBF) demonstrated the formation of bone-like apatite surface layers in both uncoated and coated scaffolds. Overall, the produced scaffolds exhibit promising properties for bone tissue engineering applications.

Evolution of Oxygen-Ion and Proton Conductivity in Ca-Doped Ln2Zr2O7 (Ln = Sm, Gd), Located Near Pyrochlore-Fluorite Phase Boundary.

Sm2-xCaxZr2O7-x/2 (x = 0, 0.05, 0.1) and Gd2-xCaxZr2O7-x/2 (x = 0.05, 0.1) mixed oxides in a pyrochlore-fluorite morphotropic phase region were prepared via the mechanical activation of oxide mixtures, followed by annealing at 1600 °C. The structure of the solid solutions was studied by X-ray diffraction and refined by the Rietveld method, water content was determined by thermogravimetry (TG), their bulk and grain-boundary conductivity was determined by impedance spectroscopy in dry and wet air (100-900 °C), and their total conductivity was measured as a function of oxygen partial pressure in the temperature range: 700-950 °C. The Sm2-xCaxZr2O7-x/2 (x = 0.05, 0.1) pyrochlore solid solutions, lying near the morphotropic phase boundary, have proton conductivity contribution both in the grain bulk and on grain boundaries below 600 °C, and pure oxygen-ion conductivity above 700 °C. The 500 °C proton conductivity contribution of Sm2-xCaxZr2O7-x/2 (x = 0.05, 0.1) is ~ 1 × 10-4 S/cm. The fluorite-like Gd2-xCaxZr2O7-x/2 (x = 0.1) solid solution has oxygen-ion bulk conductivity in entire temperature range studied, whereas proton transport contributes to its grain-boundary conductivity below 700 °C. As a result, of the morphotropic phase transition from pyrochlore Sm2-xCaxZr2O7-x/2 (x = 0.05, 0.1) to fluorite-like Gd2-xCaxZr2O7-x/2 (x = 0.05, 0.1), the bulk proton conductivity disappears and oxygen-ion conductivity decreases. The loss of bulk proton conductivity of Gd2-xCaxZr2O7-x/2 (x = 0.05, 0.1) can be associated with the fluorite structure formation. It is important to note that the degree of Ca substitution in such solid solutions (Ln2-xCax)Zr2O7-δ (Ln = Sm, Gd) is low, x < 0.1. In both series, grain-boundary conductivity usually exceeds bulk conductivity. The high grain-boundary proton conductivity of Ln2-xCaxZr2O7-x/2 (Ln = Sm, Gd; x = 0.1) is attributable to the formation of an intergranular CaZrO3-based cubic perovskite phase doped with Sm or Gd in Zr sublattice.

Injectable MnSr-doped brushite bone cements with improved biological performance.

Good mechanical properties and high injectability are the major requirements to ensure widespread application of calcium phosphate cements (CPCs) as bone substitutes in minimally invasive surgeries. However, obtaining CPCs that exhibit a good compromise between these two properties as well as good biological performance is still a great challenge. This study presents novel solutions to improve these properties, which include (i) co-doping ß-tricalcium phosphate (ß-TCP) powder with Sr and Mn, and (ii) adding small amounts of saccharides (sucrose or fructose) to the setting-liquid solution. The combination of these two strategies enabled full injectability and significantly increased the wet compressive strength of CPCs in comparison to undoped or solely Sr-doped CPCs. Furthermore, the proliferative response of human MG63 osteoblastic cells, their rate of collagen-I secretion, and particularly their growth behaviour on the cement surfaces were also enhanced. The overall improved relevant properties of Mn/Sr co-doped CPCs with added sucrose, including in vitro biological performance, renders them very promising materials for bone regeneration and tissue engineering.

Effects of Mn-doping on the structure and biological properties of ß-tricalcium phosphate.

Doping calcium phosphates with trace elements that exist in bone tissues is beneficial in terms of cell-material interactions and in vivo performance of the bone grafts made thereof. Manganese (Mn) is an essential element for normal growth and metabolism of bone tissues, but studies reporting the effects of Mn-doping calcium phosphates are scarce. The present study investigated the influence of Mn-doping on the structure, morphology and biological properties of ß-tricalcium phosphate [ß-Ca3(PO4)2] (ß-TCP). Mn-doped (MnTCP) powders, with Mn contents varying from 0 to 10 mol%, were obtained through an aqueous precipitation method followed by heat treatment at 800 °C. The successful incorporation of Mn into ß-TCP structure was proved through quantitative X-ray diffraction (XRD) phase analysis coupled with structural Rietveld refinement. Increasing Mn concentrations led to decreasing trends of a- and c-axis lattice parameters, and Mn-doping also significantly affected the morphology of ß-TCP powders. In vitro proliferation and differentiation assays of MC3T3-E1 osteoblastic-like cells, grown in the presence of the powders, revealed that the biological benefits of Mn-doped ß-TCP are limited to lower Mn incorporation levels and potentially related to their surface microstructure. The Mn1-ßTCP composition revealed the best set of bioactivity properties, potentially a good candidate for future applications of ß-TCP materials in osteoregeneration.