Maturation of biomimetic hydroxyapatite in physiological fluids: a physicochemical and proteomic study

Biomimetic calcium-deficient hydroxyapatite (CDHA) as a bioactive material exhibits exceptional intrinsic osteoinductive and osteogenic properties because of its nanostructure and composition, which promote a favorable microenvironment. Its high reactivity has been hypothesized to play a relevant role in the in vivo performance, mediated by the interaction with the biological fluids, which is amplified by its high specific surface area. Paradoxically, this high reactivity is also behind the in vitro cytotoxicity of this material, especially pro-nounced in static conditions. The present work explores the structural and physicochemical changes that CDHA undergoes in contact with physiological fluids and to investigate its interaction with proteins. Calcium-deficient hydroxyapatite discs with different micro/nanostructures, coarse (C) and fine (F), were exposed to cell-free complete culture medium over extended periods of time: 1, 7, 14, 21, 28, and 50 days. Precipitate formation was not observed in any of the materials in contact with the physiological fluid, which would indicate that the ionic exchanges were linked to incorporation into the crystal structure of CDHA or in the hydrated layer. In fact, CDHA experienced a maturation process, with a progressive increase in crystallinity and the Ca/P ratio, accompanied by an uptake of Mg and a B-type carbonation process, with a gradual propagation into the core of the samples. However, the reactivity of biomimetic hydroxyapatite was highly dependent on the specific surface area and was amplified in nanosized needle-like crystal structures (F), whereas in coarse specimens the ionic exchanges were restricted to the surface, with low penetration in the material bulk. In addition to showing a higher protein adsorption on F substrates, the proteomics study revealed the existence of protein selectivity to-ward F or C microstructures, as well as the capability of CDHA, and more remarkably of F-CDHA, to concentrate specific proteins from the culture medium. Finally, a substantial improvement in the material's ability to support cell proliferation was observed after the CDHA maturation process

Biomaterials

És ben sabut que la Ciència i Tecnologia dels Biomaterials és una disciplina de creació molt recent. Fins al punt que encara no existeix una normativa sòlida relativa a l'avaluació de la biocomptabilitat dels biomaterials. El treball que presentem pretén introduir el concepte de biomaterial i descriure'n els tipus i les aplicacions mèdiques i quirúrgiques. Els biomaterials conformen una àrea interdisciplinària en què han d'intervenir tant enginyers mecànics i de materials com dissenyadors, biòlegs cel.lulars, metges i cirurgians. La característica que ha de complir qualsevol biomaterial és ser biocompatible

Biomateriales

Es bien sabido que la Ciencia y la Tecnología de los Biomateriales es muy reciente. Tanto es así que todavía no existe una sòlida normativa relativa a la evaluación de la biocompatibilidad de los biomateriales. El presente trabajo pretende introducir el concepto de Biomaterial, así como describir sus tipos y sus aplicaciones médicas y quirúrgicas. El tema de los Biomateriales es un área interdisciplinaria donde deben intervenir tanto ingenieros mecánicos y de materiales, como diseñadores y biólogos celulares, así como médicos y cirujanos. La característica que debe cumplir todo biomaterial es ser biocompatible. En consecuencia se analiza de biocompatibilidad y las técnicas habituales para evaluarla

Critical review: Injectability of calcium phosphate pastes and cements

Calcium phosphate cements (CPC) have seen clinical success in many dental and orthopaedic applications in recent years. The properties of CPC essential for clinical success are reviewed in this article, which includes properties of the set cement (e.g. bioresorbability, biocompatibility, porosity and mechanical properties) and unset cement (e.g. setting time, cohesion, flow properties and ease of delivery to the surgical site). Emphasis is on the delivery of calcium phosphate (CaP) pastes and CPC, in particular the occurrence of separation of the liquid and solid components of the pastes and cements during injection; and established methods to reduce this phase separation. In addition a review of phase separation mechanisms observed during the extrusion of other biphasic paste systems and the theoretical models used to describe these mechanisms are discussed

Low temperature method for the production of calcium phosphate fillers

BACKGROUND: Calcium phosphate manufactured samples, prepared with hydroxyapatite, are used as either spacers or fillers in orthopedic surgery, but these implants have never been used under conditions of mechanical stress. Similar conditions also apply with cements. Many authors have postulated that cements are a useful substitute material when implanted in vivo. The aim of this research is to develop a low cristalline material similar to bone in porosity and cristallinity. METHODS: Commercial hydroxyapatite (HAp) and monetite (M) powders are mixed with water and compacted to produce cylindrical samples. The material is processed at a temperature of 37–120 degrees C in saturated steam to obtain samples that are osteoconductive. The samples are studied by X-ray powder diffraction (XRD), Vickers hardness test (HV), scanning electron microscopy (SEM), and porosity evaluation. RESULTS: The X-ray diffractions of powders from the samples show patterns typical of HAp and M powders. After thermal treatment, no new crystal phase is formed and no increase of the relative intensity of the peaks is obtained. Vicker hardness data do not show any relationship with treatment temperature. The total porosity decreases by 50–60% according to the specific thermal treatment. Scanning electron microscopy of the surfaces of the samples with either HAp 80%-M 20% (c) or Hap 50%-M 50% (f), show cohesion of the powder grains. CONCLUSIONS: The dissolution-reprecipitation process is more intesive in manufactured samples (c) and (f), according to Vickers hardness data. The process occurs in a steam saturated environment between 37 degrees and 120 degrees C. (c) (f) manufactured samples show pore dimension distributions useful to cellular repopulation in living tissues

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats

Novel composite implant in craniofacial bone reconstruction

Bioactive glass (BAG) and polymethyl methacrylate (PMMA) have been used in clinical applications. Antimicrobial BAG has the ability to attach chemically to surrounding bone, but it is not possible to bend, drill or shape BAG during the operation. PMMA has advantages in terms of shaping during the operation, but it does not attach chemically to the bone and is an exothermic material. To increase the usefulness of BAG and PMMA in skull bone defect reconstructions, a new composite implant containing BAG and PMMA in craniofacial reconstructions is presented. Three patients had pre-existing large defects in the calvarial and one in the midface area. An additive manufacturing (AM) model was used preoperatively for treatment planning and custom-made implant production. The trunk of the PMMA implant was coated with BAG granules. Clinical and radiological follow-up was performed postoperatively at 1 week, and 3, 6 and 12 months, and thereafter annually up to 5 years. Computer tomography (CT) and positron emission tomography (PET-CT) were performed at 12 and 24 months postoperatively. Uneventful clinical recovery with good esthetic and functional outcome was seen. CT and PET-CT findings supported good clinical outcome. The BAG–PMMA implant seems to be a promising craniofacial reconstruction alternative. However, more clinical experience is needed

Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin

In bone disorders infections are common. The concentration of majority of antibiotics is very low in the bone tissue. A high local dose can be obtained from the ciprofloxacin-loaded hydroxyapatite nanoparticles. The present study is aimed at developing the use of hydroxyapatite and zinc-doped hydroxyapatite nanoparticles as a carrier for ciprofloxacin drug delivery system. The ciprofloxacin-loaded hydroxyapatite and zinc-doped hydroxyapatite have a good antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus. Hydroxyapatite and zinc-doped hydroxyapatite were prepared and characterized using X-ray diffraction, Transmission electron microscopy and inductively coupled plasma optical emission spectrometry. They were loaded with ciprofloxacin using optimized drug loading parameters. Drug loading, in vitro drug release and antimicrobial activity were analyzed. The influence of zinc on the controlled release of ciprofloxacin was analyzed. The results show that the presence of zinc increases the drug release percentage and that the drug was released in a controlled manner