Marta Cerruti

Biocompatibility and biodegradability of Mg-Sr alloys: the formation of Sr-substituted hydroxyapatite.

Magnesium is an attractive material for use in biodegradable implants due to its low density, non-toxicity and mechanical properties similar to those of human tissue such as bone. Its biocompatibility makes it amenable for use in a wide range of applications from bone to cardiovascular implants. Here we investigated the corrosion rate in simulated body fluid (SBF) of a series of Mg-Sr alloys, with Sr in the range of 0.3-2.5%, and found that the Mg-0.5 Sr alloy showed the slowest corrosion rate. The degradation rate from this alloy indicated that the daily Sr intake from a typical stent would be 0.01-0.02 mg day⁻¹, which is well below the maximum daily Sr intake levels of 4 mg day⁻¹. Indirect cytotoxicity assays using human umbilical vascular endothelial cells indicated that Mg-0.5 Sr extraction medium did not cause any toxicity or detrimental effect on the viability of the cells. Finally, a tubular Mg-0.5 Sr stent sample, along with a WE43 control stent, was implanted into the right and left dog femoral artery. No thrombosis effect was observed in the Mg-0.5 Sr stent after 3 weeks of implantation while the WE43 stent thrombosed. X-ray diffraction demonstrated the formation of hydroxyapatite and Mg(OH)₂ as a result of the degradation of Mg-0.5 Sr alloy after 3 days in SBF. X-ray photoelectron spectroscopy further showed the possibility of the formation of a hydroxyapatite Sr-substituted layer that presents as a thin layer at the interface between the Mg-0.5 Sr alloy and the corrosion products. We believe that this interfacial layer stabilizes the surface of the Mg-0.5 Sr alloy, and slows down its degradation rate over time.

Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery

Drug administration via buccal mucosa is an attractive drug delivery strategy due to good patient compliance, prolonged localized drug effect, and avoidance of gastrointestinal drug metabolism and first-pass elimination. Buccal drug delivery systems need to maintain an intimate contact with the mucosa lining in the wet conditions of the oral cavity for long enough to allow drug release and absorption. For decades, mucoadhesive polymers such as chitosan (CS) and its derivatives have been explored to achieve this. In this study, inspired by the excellent wet adhesion of marine mussel adhesive protein, we developed a buccal drug delivery system using a novel catechol-functionalized CS (Cat-CS) hydrogel. We covalently bonded catechol functional groups to the backbone of CS, and crosslinked the polymer with a non-toxic crosslinker genipin (GP). We achieved two degrees of catechol conjugation (9% and 19%), forming Cat9-CS/GP and Cat19-CS/GP hydrogels, respectively. We confirmed covalent bond formation during the catechol functionalization and GP crosslinking during the gel formation. The gelation time and the mechanical properties of Cat-CS hydrogels are similar to those of CS only hydrogels. Catechol groups significantly enhanced mucoadhesion in vitro (7 out of the 10 Cat19-CS hydrogels were still in contact with porcine mucosal membrane after 6 h, whereas all of the CS hydrogels lost contact after 1.5 h). The new hydrogel systems sustained the release of lidocaine for about 3 h. In-vivo, we compared buccal patches made of Cat19-CS/GP and CS/GP adhered to rabbit buccal mucosa. We were able to detect lidocaine in the rabbits serum at concentration about 1 ng/ml only from the Cat19-CS patch, most likely due to the intimate contact provided by mucoadhesive Cat19-CS/GP systems. No inflammation was observed on the buccal tissue in contact with any of the patches tested. These results show that the proposed catechol-modified CS hydrogel is a promising mucoadhesive and biocompatible hydrogel system for buccal drug delivery.

Dependence of plasmon polaritons on the thickness of indium tin oxide thin films

The evolution of polariton features with increasing thickness in p-polarized (TM) reflectance spectra of indium tin oxide (ITO) thin films deposited on BK7 glass reveals the nature of plasmons in conducting thin films without interference from band-to-band transitions or the tendency of very thin films to form islands, both of which are complicating factors with the noble metals Au and Ag. Although the dependence on energy, film thickness, and angle of incidence is complex, these features are accurately described by the three-phase (substrate/overlayer/ambient) Fresnel model using only the Drude free-electron representation for the dielectric function of the ITO film. For film thicknesses less than 80nm the relevant excitation is a one-dimensional screened-bulk plasmon (SBP) that corresponds to charge transfer across the entire film. The associated SBP polariton (SBPP) occurs at the energy of the SBP and is relatively independent of the angle of incidence. For film thicknesses greater than 120nm, the rele...

Hydrogen peroxide whitens teeth by oxidizing the organic structure

OBJECTIVES The mechanism of tooth bleaching using peroxide oxidizers is not fully understood. It is unknown whether peroxide radicals make teeth whiter by deproteinizing, demineralizing, or oxidizing tooth tissues. This study was designed to define the mechanism of tooth bleaching and determine which of tooth enamel chemical components is/are affected by bleaching. METHODS Sixty sound teeth were collected from adult patients. The teeth were divided into 6 equal groups (n=10). Groups 1, 2, 3 and 4 were treated for 4 days with one of the following solutions: deproteinizing (NaOH) that removes organic content, demineralizing (EDTA) that decalcifies the mineral content, oxidizing (H(2)O(2)) and distilled water (control). Group 5 and 6 were pre-treated with either deproteinizing or demineralizing solutions before treating them with oxidizing solutions for 4 days. Changes in enamel elemental ratios, crystallinity index and tooth shade parameters of the treated teeth were examined by means of EDS, Raman spectroscopy and shade-spectrophotometry. The data obtained was analysed with Wilcoxon Signed-Ranks Test, and the statistical significance was set at p<0.05. RESULTS Tooth deproteinization increased the lightness by 4.8 ± 2.7°, tooth demineralization resulted in 8.5 ± 5.6° decrease in the lightness and tooth oxidization induced 19.9 ± 6.5° increase in the lightness. Oxidization of the deproteinized teeth did not influence shade parameters, but oxidation of the demineralized teeth resulted in 10.7 ± 5.8° increase in the lightness. CONCLUSION Hydrogen peroxide does not induce significant changes in tooth enamel organic and inorganic relative contents, and it whitens teeth just by oxidizing their organic matrix. These findings are of great clinical significance since they explain the mechanism of tooth bleaching, and help understanding its limitations and disadvantages.

Plasmonic phenomena in indium tin oxide and ITO-Au hybrid films

The observation of surface-plasmon resonances in indium tin oxide (ITO) thin films is complemented with the effects of hybrid ITO/Au conducting layers where charge densities can be tuned. Where carrier densities are similar (ITO and nanoparticle Au), the plasmonic behavior is that of a monolithic ITO thin film. Where the carrier density of one layer is much greater than that of the other (ITO and Au metal), boundary conditions lead to cancelation of the surface plasmon. In the latter case a capacitivelike plasmon resonance is observed for sufficiently thin films.

Polymer-oligopeptide composite coating for selective detection of explosives in water.

The selective detection of a specific target molecule in a complex environment containing potential contaminants presents a significant challenge in chemical sensor development. Utilizing phage display techniques against trinitrotoluene (TNT) and dinitrotoluene (DNT) targets, peptide receptors have previously been identified with selective binding capabilities for these molecules. For practical applications, these receptors must be immobilized onto the surface of sensor platforms at high density while maintaining their ability to bind target molecules. In this paper, a polymeric matrix composed of poly(ethylene-co-glycidyl methacrylate) (PEGM) has been prepared. A high density of receptors was covalently linked through reaction of amino groups present in the receptor with epoxy groups present in the co-polymer. Using X-ray photoelectron spectroscopy (XPS) and gas-chromatography/mass spectroscopy (GC/MS), this attachment strategy is demonstrated to lead to stably bound receptors, which maintain their selective binding ability for TNT. The TNT receptor/PEGM conjugates retained 10-fold higher TNT binding ability in liquid compared to the lone PEGM surface and 3-fold higher TNT binding compared to non-specific receptor conjugates. In contrast, non-target DNT exposure yielded undetectable levels of binding. These results indicate that this polymeric construct is an effective means of facilitating selective target interaction both in an aqueous environment. Finally, real-time detection experiments were performed using a quartz crystal microbalance (QCM) as the sensing platform. Selective detection of TNT vs DNT was demonstrated using QCM crystals coated with PEGM/TNT receptor, highlighting that this receptor coating can be incorporated as a sensing element in a standard detection device for practical applications.

Conductive oxide thin films: Model systems for understanding and controlling surface plasmon resonance

Degeneratively doped conductive oxides represent a unique host for exploring the inter-relationship between the properties of charge carriers and their collective plasmonic response. These materials often lack interband transitions that obfuscate interpretation of spectral response in elemental metals, and unlike metals, the electronic transport properties of conductive oxides are easily tunable. This work explores the process-structure-property relationships that regulate surface plasmon resonance (SPR) in sputter deposited indium tin oxide (ITO) thin films. Film deposition conditions are used to regulate film microstructure and tune the electronic mobility to between 7 and 40 cm2 V−1 s−1. Postdeposition annealing in low oxygen partial pressure atmospheres is used to engineer the ITO defect equilibrium and modulate carrier concentrations to between 1020 and 1021 cm−3. These electronic transport properties are modulated with near independence enabling straightforward interpretation of their influence on t...

Characterization of sol–gel bioglasses with the use of simple model systems: a surface-chemistry approach

The present work deals with the physico-chemical characterization of the surface features of two powdery sol–gel-synthesized bioglass specimens (58S and 77S) employed in repair of human bones and soft tissues. In-situ transmission FTIR spectroscopy and adsorption microcalorimetry (with the use of water as a probe molecule) were adopted in parallel to study on one hand bioglasses (amorphous Si, Ca and P oxides) and on the other hand pure and doped silica specimens, as reference materials. It was observed that the presence of Ca and P moieties induces the formation of surface sites that possess higher strength and higher capability towards water coordination than do the hydroxy groups present on pure silica. In particular, the presence of some irreversibly coordinated water was observed both on these bioglasses and on doped silica. The Ca/P ratio seems to play a major role: (i) an excess of Ca induces the presence of coordinatively unsaturated surface (cus) Ca2+ ions, that generate Lewis acid sites that can strongly interact with water and can yield surface carbonates; (ii) the presence of P species increases the surface hydrophilic character and leads to the formation of Si–O–P labile bridges, which exhibit an enhanced propensity to dissociate water.

The importance of amino acid interactions in the crystallization of hydroxyapatite.

Non-collagenous proteins (NCPs) inhibit hydroxyapatite (HA; Ca5(PO4)3OH) formation in living organisms by binding to nascent nuclei of HA and preventing their further growth. Polar and charged amino acids (AAs) are highly expressed in NCPs, and the negatively charged ones, such as glutamic acid (Glu) and phosphoserine (P-Ser) seem to be mainly responsible for the inhibitory effect of NCPs. Despite the recognized importance of these AAs on the behaviour of NCPs, their specific effect on HA crystallization is still unclear, and controversial results have been reported concerning the efficacy of HA inhibition of positively versus negatively charged AAs. We focused on a positively charged (arginine, Arg) and a negatively charged (Glu) AA, and their combination in the same solution. We studied their inhibitory effect on HA nucleation and growth at physiological temperature and pH and we determined the mechanism by which they can affect HA crystallization. Our results showed a strong inhibitory effect of Arg on HA nucleation; however, Glu was more effective in inhibiting HA crystal growth during the growth stage. The combination of Glu and Arg was less effective in controlling HA nucleation, but it inhibited HA crystal growth. We attributed these differences to the stability of complexes formed between AAs and calcium and phosphate ions at the nucleation stage, and in bonding strength of AAs to HA crystal faces during the growth stage. The AAs also influenced the morphology of synthesized HA. Presence of either Arg or Glu resulted in the formation of spherulites consisting of preferentially oriented nanoplatelets orientation. This was attributed to kinetic factors favoring growth front nucleation (GFN) mechanism.

Mollusk Glue Inspired Mucoadhesives for Biomedical Applications

Chitosan (CH), partially N-deacetylated chitin, is a biodegradable and biocompatible polymer that has shown great potential in drug delivery and tissue engineering applications. Although bioadhesive, CH has limited mucoadhesion in wet conditions due to weak interactions with biological surfaces. DOPA (3,4-dihydroxy-L-phenylalanine), a catechol-containing molecule naturally present in marine mussel foot proteins, has been shown to increase the mucoadhesion of several polymers. We report here a simple and bioinspired approach to enhance CH mucoadhesion in wet conditions by preparing mixed hydrogels including CH and different catechol-containing compounds, namely DOPA, hydrocaffeic acid (HCA), and dopamine (DA). We characterized the hydrogels for their swelling, release kinetics of the catechol compounds, and mucoadhesive strength to rabbit small intestine. The swelling of the hydrogels was pH dependent with maximum swelling at pH 1. The hydrogel swelling was higher in the presence of the DOPA and DA but lower in the presence of HCA. HCA/CH hydrogel also showed the slowest catechol release, most likely due to electrostatic interactions between CH and HCA. Lower hydrogel swelling and slower HCA release resulted in increased mucoadhesion: HCA/CH showed more than 2-fold enhancement of mucoadhesion to rabbit small intestine compared to CH alone. Since it is known that catechol compounds can be oxidized, we analyzed the oxidation of DOPA, HCA, and DA at different pH values and its effect on mucoadhesion. We found that oxidation occurring before contact with the intestinal mucosa did not improve mucoadhesion, while oxidation occurring during the contact further increased the mucoadhesion of HCA/CH hydrogels. These results show that mucoadhesion of CH hydrogels can be increased with a simple bioinspired approach, which has the potential to be applied to other polymers since it does not require any chemical modification.