Ferdinando Papale

Influence of the polymer amount on bioactivity and biocompatibility of SiO2/PEG hybrid materials synthesized by sol-gel technique.

SiO2/PEG organic-inorganic hybrid materials, which differ in polyethylene glycol (PEG) content, were synthesized by sol-gel technique and the characterization of their structure and biological properties was carried out in order to evaluate the possible use in biomedical field. FT-IR spectroscopy detected that the two components of the hybrids (SiO2 and PEG) are linked by hydrogen bonds between the Si-OH groups of the inorganic phase and the terminal alcoholic groups and/or the ethereal oxygen atoms in the repeating units of polymer. X-ray diffraction analysis ascertained the amorphous nature of the gels and the observation of their morphology by SEM microscopy confirmed that the interpenetration of the two phases (organic and inorganic) occurs on nanometric scale. The biological characterization was carried out as a function of the polymer amount to study its influence on material behavior. The results showed that the synthesized materials were bioactive and biocompatible. The formation of a hydroxyapatite layer, indeed, was observed on their surface by SEM/EDX analysis after soaking in simulated body fluid. Moreover, the biocompatibility of SiO2/PEG hybrids was assessed performing MTT and SRB cytotoxicity tests on fibroblast cell NIH 3T3 after 24 and 48h of exposure, as well as Trypan Blue dye exclusion test. The response to the presence of the investigated materials was positive. The cell growth and proliferation showed dependence on polymer amount and time of exposure to the material extracts. Therefore, the obtained results are encouraging for the use of the obtained hybrids in dental or orthopedic applications.

Synthesis of SiO2 and CaO rich calcium silicate systems via sol-gel process: Bioactivity, biocompatibility, and drug delivery tests

Silica and calcium silicate amorphous materials, mixed with sodium ampicillin, a broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. The bioactivity of the synthesized materials has been put into evidence by the appearance of a crystal of hydroxyapatite on the surface of the samples soaked in a fluid simulating the composition of the human blood plasma, as detected through FTIR measurements and SEM micrographs. The present work refers to a series of in-vitro biocompatibility tests, which has been performed on silicate and CaO rich calcium silicate gel-glasses, to study the cell behavior when seeded on 1 cm(2) material fragments, introduced into an in-vitro culture system. 3T3 cell lines have been used and the viability has been evaluated by WST-8 test. The composition of the adopted glasses can be expressed by the following general formula: x CaO• (1 - x) SiO2 with x = 0.00; 0.30; 0.40; 0.50; 0.60. Subsequently, release kinetics in a simulate body fluid (SBF) has been investigated. The amount of sodium ampicillin released has been detected by UV-Vis spectroscopy. The release kinetics has appeared to occur in more than one stage. All data have shown that those materials could be used as drug delivery bioactive systems.

Biological response of human mesenchymal stromal cells to titanium grade 4 implants coated with PCL/ZrO2 hybrid materials synthesized by sol–gel route: in vitro evaluation

The surface modification of implantable materials in order to improve their biological proprieties, including tissue tolerance and osseointegration ability, by means of functional coating deposition is a promising strategy to provide a firm fixation of the implants. In this study, organic/inorganic hybrid materials consisting of an inorganic zirconia-based matrix, in which a biocompatible polymer, poly(ε-caprolactone) (PCL), has been incorporated at different percentages, have been synthesized via sol-gel route. Developed materials have been used to coat titanium grade 4 substrates by means of dip coating technique. Scanning electron microscopy (SEM) analysis of the obtained coatings has shown that films crack-free can be obtained for high levels of PCL. Chemical composition and interactions between organic and inorganic moieties have been studied by Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy. The bone-bonding capability of the nanocomposite films has been evaluated in vitro by examining the appearance of an apatite layer on their surface when soaked in a simulated body fluid by means of SEM equipped with EDS microanalysis. In vitro biocompatibility assessment was performed in combination with human mesenchymal stromal cells (hMSCs). Materials were found to be non-toxic and supporting cell proliferation. Additionally, the coating material was not hampering the differentiation of hMSCs in an osteogenic medium.

Preparation, characterization, and biological properties of organic-inorganic nanocomposite coatings on titanium substrates prepared by sol-gel.

When surface-reactive (bioactive) coatings are applied to medical implants by means of the sol-gel dip-coating technique, the biological proprieties of the surface of the implant can be locally modified to match the properties of the surrounding tissues to provide a firm fixation of the implant. The aim of this study has been to synthesize, via sol-gel, organoinorganic nanoporous materials and to dip-coat a substrate to use in dental applications. Different systems have been prepared consisting of an inorganic zirconium-based matrix, in which a biodegradable polymer, the poly-ε-caprolactone was incorporated in different percentages. The materials synthesized by the sol-gel process, before gelation, when they were still in sol phase, have been used to coat a titanium grade 4 (Ti-4) substrate to change its surface biological properties. Thin films have been obtained by means of the dip-coating technique. A microstructural analysis of the obtained coatings was performed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy. The biological proprieties have been investigated by means of tests in vitro. The bone-bonding capability of the nanocomposite films has been evaluated by examining the appearance of apatite on their surface when plunged in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. The examination of apatite formation on the nanocomposites, after immersion in SBF, has been carried out by SEM equipped with energy-dispersive X-ray spectroscopy. To evaluate cells-materials interaction, human osteosarcoma cell line (Saos-2) has been seeded on specimens and cell vitality evaluated by WST-8 assay.

Biological evaluation of zirconia/PEG hybrid materials synthesized via sol-gel technique

The objective of the following study has been the synthesis via sol-gel and the characterization of novel organic-inorganic hybrid materials to be used in biomedical field. The prepared materials consist of an inorganic zirconia matrix containing as organic component the polyethylene glycol (PEG), a water-soluble polymer used in medical and pharmaceutical fields. Various hybrids have been synthesized changing the molar ratio between the organic and inorganic parts. Fourier transform spectroscopy suggests that the structure of the interpenetrating network is realized by hydrogen bonds between the Zr-OH group in the sol-gel intermediate species and both the terminal alcoholic group and ethereal oxygen atoms in the repeating units of polymer The amorphous nature of the gels has been ascertained by X-ray diffraction analysis. The morphology observation has been carried out by using the Scanning Electron Microscope and has confirmed that the obtained materials are nanostructurated hybrids. The bioactivity of the synthesized system has been shown by the formation of a hydroxyapatite layer on the surface of samples soaked in a fluid simulating the human blood plasma. The potential biocompatibility of hybrids has been assessed as performing indirect MTT cytotoxicity assay towards 3T3 cell line at 24, 48, and 72 h exposure times.

TiO2/PCL hybrid materials synthesized via sol-gel technique for biomedical applications.

The aim of the present work has been the synthesis of organic/inorganic hybrid materials based on titanium dioxide and poly(ε-caprolactone) (PCL) to be used in the biomedical field. Several materials have been synthesized using sol-gel methods by adding different amounts of polymer to the inorganic sol. The obtained gels have been characterized using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). The FT-IR data allowed us to hypothesize that the structure formed was that of an interpenetrating network, realized by hydrogen bonds between TiOH groups in the sol-gel intermediate species and carbonyl groups in the polymer repeating units. SEM and AFM analyses highlighted that the obtained materials were nanostructurated hybrids. To evaluate the biological properties of the hybrids, their bioactivity and cytotoxicity were investigated as a function of the PCL amount. The bioactivity of the synthesized systems was proven by the formation of a hydroxyapatite layer on the surface of samples soaked in a fluid simulating human blood plasma (SBF). MTT cytotoxicity tests and Trypan Blue dye exclusion tests were carried out exposing NIH-3T3 mouse embryonic fibroblasts for 24 and 48h to extracts from the investigated hybrid materials. The results showed that all the hybrids had a non-cytotoxic effect on target cells.

Silica–polyethylene glycol hybrids synthesized by sol–gel: Biocompatibility improvement of titanium implants by coating

Although metallic implants are the most used in dental and orthopaedic fields, they can early fail due to low tissue tolerance or osseointegration ability. To overcome this drawback, functional coatings can be applied on the metallic surface to provide a firm fixation of the implants. The objective of the present study was twofold: to synthesize and to characterize silica/polyethylene glycol (PEG) hybrid materials using sol-gel technique and to investigate their capability to dip-coat titanium grade 4 (Ti-gr4) substrates to improve their biological properties. Various hybrid systems have been synthesized by changing the ratio between the organic and inorganic phases in order to study the influence of the polymer amount on the structure and, thus, on the properties of the coatings. Fourier transform infrared (FTIR) spectroscopy and solid state Nuclear Magnetic Resonance (NMR) allowed us to detect the formation of hydrogen bonds between the inorganic sol-gel matrix and the organic component. SEM analysis showed that high PEG content enables to obtain crack free-coating. Moreover, the effective improvement in biological properties of Ti-gr4 implants has been evaluated by performing in vitro tests. The bioactivity of the hybrid coatings has been showed by the hydroxyapatite formation on the surface of SiO2/PEG coated Ti-gr4 substrates after soaking in a simulated body fluid and the lack of cytotoxicity by the WST-8 Assay. The results showed that the coated substrates are more bioactive and biocompatible than the uncoated ones and that the bioactivity is not significantly affected by PEG amount whereas its addition makes the films more biocompatible.

Synthesis of zirconia/polyethylene glycol hybrid materials by sol–gel processing and connections between structure and release kinetic of indomethacin

Abstract Controlled and local drug delivery systems of anti-inflammatory agents are attracting an increasing attention because of their extended therapeutic effect and reduced side effects. In this work, the sol–gel process was used to synthesize zirconia/polyethylene glycol (ZrO2/PEG) hybrid materials containing indomethacin for controlled drug delivery. Different percentages of PEG were introduced in the synthesis to modulate the release kinetic and an exhaustive chemical characterization of all samples was performed to detect the relationship between their structure and release ability. Fourier transform spectroscopy and solid-state NMR show that the Zr–OH groups of the inorganic matrix bond both the ethereal oxygen atoms of the polymer and the carboxylic groups of the drug. X-ray diffraction analysis ascertains the amorphous nature of those materials. Scanning electron microscopy detects the nanostructure and the homogeneous morphology of the synthesized materials. The bioactivity was demonstrated by the formation of a hydroxyapatite layer on the surface of the samples, after soaking in a simulated body fluid. The release kinetics study, performed by HPLC UV–Vis spectroscopy, proves that the release ability depends on PEG and the drug amount and also demonstrates the indomethacin integrity after the synthetic treatment.

Synthesis of SiO2 system via sol-gel process: biocompatibility tests with a fibroblast strain and release kinetics.

SiO2 glass has been synthesized via sol-gel process and enriched with 5 wt % sodium ampicillin. To verify the biocompatibility of the obtained biomaterial, fibroblasts have been grown on a glass surface and were tested for viability after 24 h. The results of the Water-Soluble Tetrazolium (WST)-8 analysis suggest that SiO2 glass has an adequate biocompatibility. The amorphous nature of the gels has been ascertained by X-ray diffraction analysis. Release kinetics have been subsequently investigated in a simulated body fluid. The amount of sodium ampicillin released has been detected by ultraviolet-visible spectroscopy. The release kinetics seems to occur in more than one stage. High-performance liquid chromatography analysis has also been carried out to ensure the integrity of ampicillin after the synthesis treatment.

Synthesis and chemical characterization of new silica polyethylene glycol hybrid nanocomposite materials for controlled drug delivery

A series of inorganic organic hybrid nanocomposite materials, containing indomethacin (IND) as a model drug, were synthesized using an inorganic precursor (tetraethoxysilane, TEOS) and an organic precursor (polyethylene glycol, PEG 400) through sol-gel chemistry. The various synthesized hybrids differed in PEG weight percentage (0, 6, 12, 24, and 50 % wt). On an equal PEG percentage, different amounts of the non-steroidal anti-inflammatory drug were loaded (5, 10, and 15 % wt). The bonding characteristics of the various composites were investigated via FT-IR spectroscopy, which suggests the formation of H-bonds between hybrids components. X-ray diffraction (XRD), used for the investigation of their atomic organization, and scanning electron microscopy (SEM) analysis confirmed the amorphous and nanocomposite structure of synthesized materials, which appeared morphologically homogeneous. The in vitro bioactivity evaluation was carried out by analyzing the apatite layers produced on the hybrid materials using SBF as incubation medium. The apatite formation was analyzed using SEM coupled to energy-dispersive electron X-ray spectroscopy. The in vitro release of indomethacin from the new drug-loaded bioactive materials was investigated by HPLC-UV-ESI MS/MS analysis. Data obtained allowed us to state that the drug release was markedly affected by the PEG percentage in investigated hybrid materials.