Simone Sprio

Densification behaviour and mechanisms of synthetic hydroxyapatites

Starting from Ca(OH)2 and H3PO4 hydroxyapatite powders with three different crystallinity degrees have been prepared and characterized. Densification extent and mechanisms were studied through dilatometric measurements in isothermal regime in the range of temperature 750–1250°C: the influence of different powder features (including the effect of calcination treatment) have been evaluated. Powder characterized by the lowest crystallinity degree has the highest densification extent; overlapping phenomena occurring during the sintering treatments are responsible for unexpectedly low values found for the shrinkage rate, which can easily lead to a misidentification of the rate controlling mechanism. An interpretation of the densification mechanism, consistent with all experimental findings, is proposed.

Intrinsic magnetism and hyperthermia in bioactive Fe-doped hydroxyapatite

The use of magnetic activation has been proposed to answer the growing need for assisted bone and vascular remodeling during template/scaffold regeneration. With this in mind, a synthesis procedure was developed to prepare bioactive (Fe2+/Fe3+)-doped hydroxyapatite (Fe-HA), endowed with superparamagnetic-like properties. This new class of magnetic hydroxyapatites can be potentially employed to develop new magnetic ceramic scaffolds with enhanced regenerative properties for bone surgery; in addition, magnetic Fe-HA can find application in anticancer therapies, to replace the widely used magnetic iron oxide nanoparticles, whose long-term cytotoxicity was recently found to reach harmful levels. An extensive physicochemical, microstructural and magnetic characterization was performed on the obtained Fe-HA powders, and demonstrated that the simultaneous addition of Fe2+ and Fe3+ ions during apatite nucleation under controlled synthesis conditions induces intrinsic magnetization in the final product, minimizing the formation of magnetite as secondary phase. This result potentially opens new perspectives for biodevices aimed at bone regeneration and for anti-cancer therapies based on hyperthermia.

Mimicking natural bio-mineralization processes: A new tool for osteochondral scaffold development

In recent years, the concept of regenerative medicine has gained great importance, particularly in the field of orthopaedics, in which current solutions are based mainly on the replacement of damaged tissues with devices that function only as structural replacements with limited regenerative capacity. New regenerative solutions can be obtained by taking inspiration from nature, which surrounds us with a multitude of organisms endowed with extraordinary performance. In particular, bio-mineralization, which is the basis of the formation of load-bearing structures in vertebrate and invertebrate organisms, can be exploited to achieve innovative devices for the repair and reconstruction of bone and osteo-cartilaginous tissues.

Magnetic Bioinspired Hybrid Nanostructured Collagen–Hydroxyapatite Scaffolds Supporting Cell Proliferation and Tuning Regenerative Process

A bioinspired mineralization process was applied to develop biomimetic hybrid scaffolds made of (Fe(2+)/Fe(3+))-doped hydroxyapatite nanocrystals nucleated on self-assembling collagen fibers and endowed with super-paramagnetic properties, minimizing the formation of potentially cytotoxic magnetic phases such as magnetite or other iron oxide phases. Magnetic composites were prepared at different temperatures, and the effect of this parameter on the reaction yield in terms of mineralization degree, morphology, degradation, and magnetization was investigated. The influence of scaffold properties on cells was evaluated by seeding human osteoblast-like cells on magnetic and nonmagnetic materials, and differences in terms of viability, adhesion, and proliferation were studied. The synthesis temperature affects mainly the chemical-physical features of the mineral phase of the composites influencing the degradation, the microstructure, and the magnetization values of the entire scaffold and its biological performance. In vitro investigations indicated the biocompatibility of the materials and that the magnetization of the super-paramagnetic scaffolds, induced applying an external static magnetic field, improved cell proliferation in comparison to the nonmagnetic scaffold.

Development of hydroxyapatite/calcium silicate composites addressed to the design of load-bearing bone scaffolds.

This work deals with the preparation of bioactive ceramic composites to be employed for the development of load-bearing bone substitutes, made of hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2), HA) and bioactive dicalcium silicate (Ca(2)SiO(4), C(2)S) as a reinforcing phase. The composite materials were prepared by Fast Hot-Pressing (FHP), which allowed the rapid sintering of monolithic ceramics at temperatures up to 1500 degrees C, well above the commonly adopted temperatures for the consolidation of hydroxyapatite (1200-1300 degrees C). The purpose was to achieve the grain coalescence of both HA and the strengthening phase, so that to obtain a homogeneous ceramic material characterized by controlled phase composition and improved mechanical strength; the dwell time was reduced as much as possible to prevent HA decomposition and excessive grain growth. The most remarkable result, in terms of phase composition, was the absence of any secondary phases in the final ceramics other than HA and C(2)S, even after sintering at 1500 degrees C. The flexure strength of the composite materials was found to be much higher than that of HA alone. Further mechanical characterization was also carried out on HA and composites, sintered in different conditions, to evaluate the elastic properties and fracture toughness, and properties close to those of mineral bone were found. These preliminary results confirmed that composites of HA and Ca(2)SiO(4) are promising for the development of bioactive load-bearing ceramic bone substitutes with controlled phase composition.

Human osteoblast behavior on as‐synthesized SiO4 and B‐CO3 co‐substituted apatite

The functional behavior of synthetic apatite, commonly used as fillers or scaffolds, depends on physical and chemical parameters, which vary in response to chemical substitutions and to thermal treatments. The effect of silicon co-substituting with carbonate ions in the apatite lattice on the properties of the as-synthesized powder and finally on human osteoblast in vitro behavior was investigated. Dose-response curves of Si-free and Si-substituted carbonated apatites (namely CHA and SiCHA-1 and SiCHA-2 with 0.88 and 0.55 wt % of Si, respectively) showed that SiCHA-1 had toxic effect, whereas CHA and SiCHA-2, at worst, hindered osteoblast proliferation, but no toxicity occurred. Subsequent experiments compared the effects of CHA and SiCHA-2 used at the doses of 0.3 and 1 mg/mL. After 7 days of treatment, both the powders stimulated cell proliferation and protein content and inhibited alkaline phosphatase activity. However, SiCHA-2 slightly stimulated osteoblast differentiation, as shown by higher calcium deposition, compared with CHA. The cell behaviors were linked to the peculiar powder characteristics. The as-synthesized powder represents the most critical system in terms of reactivity toward cells and can inform on the limits for positively exploiting the characteristics of SiCHA powders in making bone fillers or scaffolds, using no thermal treatments. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Biomimesis and biomorphic transformations: new concepts applied to bone regeneration.

In the last decades the activity of material scientists was more and more directed to the development of biomimetic scaffolds, able to drive and address cell activity towards proper differentiation and the repair of diseased human tissues. In case of bone, this requires the synthesis of three-dimensional constructs able to exchange chemical signals promoting osteogenesis and to progressively be resorbed during the formation and remodelling of new bone. Besides, particularly for the regeneration of extensive portions of bone, a morphological and mechanical biomimesis is also required, to allow cell colonization and formation of a proper vascularization tree. The healing of load-bearing bones also requires scaffolds with a hierarchically organized morphology, to provide improved biomechanical behaviour and allow a proper mechano-transduction of the mechanical stimuli down to the cell level. The present paper is an overview of the current technologies and devices developed in the last decade for the regeneration of bone tissue. In particular, novel biomimetic and biomorphic scaffolds, obtained by the controlled transformation of native ligneous structures, promise to adequately face the problem of obtaining complex hierarchical structures, not achievable otherwise by any currently existing manufacturing techniques.

Biomimetic magnesium-carbonate-apatite nanocrystals endowed with strontium ions as anti-osteoporotic trigger.

The present work investigates the preparation of biomimetic nanocrystalline apatites co-substituted with Mg, CO3 and Sr to be used as starting materials for the development of nanostructured bio-devices for regeneration of osteoporotic bone. Biological-like amounts of Mg and CO3 ions were inserted in the apatite structure to mimic the composition of bone apatite, whereas the addition of increasing quantities of Sr ions, from 0 up to 12 wt.%, as anti-osteoporotic agent, was evaluated. The chemical-physical features, the morphology, the degradation rates, the ion release kinetics as well as the in vitro bioactivity of the as-prepared apatites were fully evaluated. The results indicated that the incorporation of 12 wt.% of Sr can be viewed as a threshold for the structural stability of Mg-CO3-apatite. Indeed, incorporation of lower quantity of Sr did not induce considerable variations in the chemical structure of Mg-CO3-apatite, while when the Sr doping extent reached 12 wt.%, a dramatically destabilizing effect was detected on the crystal structure thus yielding alteration of the symmetry and distortion of the PO4. As a consequence, this apatite exhibited the fastest degradation kinetic and the highest amount of Sr ions released when tested in physiological conditions. In this respect, the surface crystallization of new calcium phosphate phase when immersed in physiological-like solution occurred by different mechanisms and extents due to the different structural chemistry of the variously doped apatites. Nevertheless, all the apatites synthesized in this work exhibited in vitro bioactivity demonstrating their potential use to develop biomedical devices with anti-osteoporotic functionality.

Pulsed plasma deposition of zirconia thin films on UHMWPE: proof of concept of a novel approach for joint prosthetic implants

Wear of ultra-high molecular weight polyethylene (UHMWPE) has been recognized as the main cause for long-term revision in joint arthroplasty. A new approach to overcome this detrimental issue is here presented: zirconia (ZrO2) thin films were directly deposited onto the surface of UHMWPE by Pulsed Plasma Deposition (PPD) technique. The obtained films were structurally, morphologically and mechanically characterized by X-ray diffraction, scanning electron microscopy and nanoindentation tests, respectively. The critical fracture load was estimated by the analysis of the indenter footprints, while the adhesion degree was evaluated by a cross-cut tape test. Zirconia films exhibited a fully cubic structure, with densely packed grains, whereas mechanical tests showed that hard, tough and well-adherent films were deposited. These preliminary results suggested the feasibility of pursuing this alternative route to improve UHMPWE performances while preserving its well-established mechanical properties.

Synthesis and mechanical behavior of β-tricalcium phosphate/titania composites addressed to regeneration of long bone segments

Bioactive tricalcium phosphate/titania ceramic composites were synthesized by pressureless air sintering of mixed hydroxyapatite and titania (TiO2) powders. The sintering process was optimized to achieve dense ceramic bodies consisting in a bioactive/bioresorbable matrix (β-tricalcium phosphate) reinforced with defined amounts of sub-micron sized titania particles. Extensive chemico-physical and mechanical characterization was carried out on the resulting composites, which displayed values of flexural strength, fracture toughness and elastic modulus in the range or above the typical ranges of values manifested by human cortical bone. It was shown that titania particles provided a toughening effect to the calcium-phosphate matrix and a reinforcement in fracture strength, in comparison with sintered hydroxyapatite bodies characterized by similar relative density. The characteristics of the resulting composites, i.e. bioactivity/bioresorbability and ability of manifesting biomimetic mechanical behavior, are features that can promote processes of bone regeneration in load-bearing sites. Hence, in the perspective of developing porous bone scaffolds with high bioactivity and improved biomechanical behavior, TCP/TiO2 composites with controlled composition can be considered as very promising biomaterials for application in a field of orthopedics where no acceptable clinical solutions still exist.