Optimized 3D printed zirconia-reinforced leucite with antibacterial coating for dental applications.

OBJECTIVES: This study aims to produce by robocasting leucite/zirconia pieces with suitable mechanical and tribological performance, convenient aesthetics, and antibacterial properties to be used in dental crown replacement. METHODS: Leucite pastes reinforced with 12.5%, 25%, and 37.5% wt. ZrO2 nanoparticles were prepared and used to print samples that after sintering were characterized in terms of density, shrinkage, morphology, porosity, mechanical and tribological properties and translucency. A coating of silver diamine fluoride (SDF) and potassium iodide (KI) was applied over the most promising material. The material's antibacterial activity and cytotoxicity were assessed. RESULTS: It was found that the increase of ZrO2 reinforcement up to 25% enhanced both microhardness and fracture toughness of the sintered composite. However, for a superior content of ZrO2, the increase of the porosity negatively affected the mechanical behaviour of the composite. Moreover, the composite with 25% ZrO2 exhibited neglectable wear in chewing simulator tests and induced the lowest wear on the antagonist dental cusps. Although this composite exhibited lower translucency than human teeth, it was three times higher than the ZrO2 glazed material. Coating this composite material with SDF+KI conferred antibacterial properties without inducing cytotoxicity. SIGNIFICANCE: Robocasting of leucite reinforced with 25% ZrO2 led to best results. The obtained material revealed superior optical properties and tribomechanical behaviour compared to glazed ZrO2 (that is a common option in dental practice). Moreover, the application of SDF+KI coating impaired S. aureus proliferation, which anticipates its potential benefit for preventing pathogenic bacterial complications associated with prosthetic crown placement.

High-performance bilayer composites for the replacement of osteochondral defects.

Osteochondral (OC) defects combine damage to cartilage and subchondral bone, posing a significant challenge to their repair due to the dissimilar characteristics and regenerative capabilities between the two tissues. Here, we propose novel OC bilayer composites, drawing inspiration from corresponding biological tissues and using a combination of simple and reproducible techniques. Cartilage-like materials based on poly(vinyl alcohol) (PVA) hydrogels were produced with nanofiber reinforcements acquired from high-performance fibers (Kevlar® and Zylon®), while bone-like materials were obtained by adding magnesium-substituted calcium phosphate ceramics to PVA. All composites were sterilized by gamma irradiation to rule out the possibility of undesirable effects resulting from the process, and then fully characterized. The results indicated that nanofibers and bioceramics incorporated into the PVA networks form promising structures with multiple interesting properties. The composites resembling cartilage and bone showed high biomimicry with natural tissues, being able to reconcile exceptional mechanics with the requirements of adequate porosity, liquid content, and biological behavior. The developed materials reveal a high potential for use in OC tissue repair applications.

Effect of albumin, urea, lysozyme and mucin on the triboactivity of Ti6Al4V/zirconia pair used in dental implants.

The titanium implant/zirconia abutment interface can suffer failure upon mechanical and biological issues, ultimately leading to the loss of the artificial tooth. The study of the effect of the organic compounds present in saliva on the tribological behavior of these systems is of utmost importance to understand the failure mechanisms and better mimic the in vivo conditions. The aim of the present work is to evaluate the effect of the addition of albumin, urea, lysozyme and mucin to artificial saliva, on the triboactivity of Ti6Al4V/zirconia pair commonly used in dental implants and then, compare the results with those obtained with human saliva. The solutions' viscosity was measured and the adsorption of the different biomolecules to both Ti6Al4V and zirconia was accessed. Tribological tests were performed using Ti6Al4V balls sliding on zirconia plates inside of a corrosion cell. Friction and wear coefficients were determined, and the open circuit potential (OCP) was monitored during the tests. Also, the wear mechanisms were identified. The presence of mucin in the artificial lubricant led to the lowest wear coefficients. The main wear mechanism was abrasion, independently of the used lubricant. Adhesive wear was observed for the systems without mucin. Tribocorrosion activity and wear coefficient were lower in the presence of mucin. None of the studied artificial lubricants mimicked the effect of human saliva (HS) on the tribological behavior of the studied pair since this lubricant led to the lowest friction coefficient and highest corrosion activity.

Polyvinyl alcohol/chitosan wound dressings loaded with antiseptics.

Wound care remains a challenge in healthcare. This work aimed to develop a new polyvinyl alcohol (PVA)/chitosan (Ch) based wound dressing able to ensure protection, hydration and a controlled release of antiseptics, as alternative to actual treatments. Two distinct formulations (1:1 and 3:1, w/w) were prepared, sterilized by autoclaving and characterized concerning surface morphology, degradation over the time, mechanical properties and hydrophilicity. Both dressings revealed adequate properties for the intended purpose. The dressings were loaded with chlorhexidine (CHX) and polyhexanide (PHMB) and the drug release profiles were determined using Franz diffusion cells. The release of PHMB was more sustained than CHX, lasting for 2 days. As the amounts of drugs released by PVA/Ch 1:1 were greater, the biological tests were done only with this formulation. The drug loaded dressings revealed antibacterial activity against S. aureus and S. epidermidis, but only the ones loaded with PHMB showed adequate properties in terms of cytotoxicity and irritability. The application of this elastic dressing in the treatment of wounds in a dog led to faster recovery than conventional treatment, suggesting that the material can be a promising alternative in wound care.

Therapeutic Ophthalmic Lenses: A Review.

An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.

Tribological performance of the pair human teeth vs 3D printed zirconia: An in vitro chewing simulation study.

This study aims to evaluate the tribological performance of the pair human teeth/robocasted zirconia, with a special focus on the enamel wear mechanisms. Zirconia pieces produced by robocasting (RC) and unidirectional compression (UC) were compared in terms of crystalline structure, density, porosity, hardness and toughness. Chewing simulation tests were performed against human dental cusps. The cusps wear was quantified and the wear mechanisms identified. Although most of the properties of UC and RC samples are similar, differences were observed for surface roughness and porosity. Although the samples did not suffer wear, the antagonist cusps worn in a similar way. In conclusion, robocasting seems a promising technique to produce customized zirconia dental pieces, namely in what concerns the overall tribological behaviour.

Suitability of 3D printed pieces of nanocrystalline zirconia for dental applications.

OBJECTIVES: The main goal of this work is to evaluate the suitability of nanostructured zirconia pieces obtained by robocasting additive manufacturing (AM), for dental applications. METHODS: The density, crystalline structure, morphology/porosity, surface roughness, hardness, toughness, wettability and biocompatibility of the produced samples were compared with those of samples obtained by conventional subtractive manufacturing (SM) of a similar commercial zirconia material. Chewing simulation studies were carried out against dental human cusps in artificial saliva. The wear of the material was quantified and the wear mechanisms investigated, as well as the influence of glaze coating. RESULTS: AM samples, that revealed to be biocompatible, are slightly less dense and more porous than SM samples, showing lower hardness, toughness and wettability than SM samples. After chewing tests, no wear was found both on AM and SM samples. However, the dental wear was significantly lower when AM samples were used as counterbody. Concerning the glazed samples, both coated surfaces and dental cusps suffered wear, being the cusps' wear higher than that found for unglazed samples. More, cusps tested against AM coated samples suffered less wear comparatively to those opposed to SM coated samples. SIGNIFICANCE: Overall, the results presented in this paper show that AM processed nanostructured zirconia can be used in dental restorations, with important advantages from the point of view of processing and tribological performance. Moreover, the option for glaze finishing should be carefully considered both in SM and AM processed specimens.

Dual drug delivery from intraocular lens material for prophylaxis of endophthalmitis in cataract surgery.

Cataract is highly prevalent among old population worldwide and replacement of the opacified crystalline lens by an intraocular lens (IOL) is the safest and the most effective treatment. Although not very frequently (0.02-0.33% of the cases), the patients who undergo cataract surgery may develop endophthalmitis, which is a serious problem eventually leading to blindness. To avoid this complication, the postoperative instillation of antibiotics and anti-inflammatories is almost universally used in clinical practice. The aim of this work was to study the possibility of loading an IOL material with an antibiotic and an anti-inflammatory, which could be simultaneously released and successfully substitute the frequent instillation of topical drops for the prevention of endophthalmitis. The IOL material commercially available under the name of CI26Y (Contamac Products) was chosen and two pairs of drugs consisting of one antibiotic and one anti-inflammatory were tested: moxifloxacin + ketorolac and moxifloxacin + diclofenac. The drug loading was done by soaking under optimized conditions. Simultaneous drug loading improved the release profiles, especially in the case of moxifloxacin + ketorolac. The effect of sterilization by steam heat (carried out on the first day of loading) and by gamma-radiation upon the release profiles was negligible. The optical and mechanical properties of the sterilized, double-loaded IOL materials were kept at adequate levels. Application of a mathematical model to predict the in vivo released concentrations suggested that the most efficient system complied with the therapeutic needs: the lens loaded with moxifloxacin + ketorolac was effective against S. aureus and S. epidermidis up to 15 days, and the amount of released ketorolac remained active against inflammation for a minimum of 16 days.

Influence of contact configuration and lubricating conditions on the microtriboactivity of the zirconia-Ti6Al4V pair used in dental applications.

Loosening and fracture of implanted dental crowns is a consequence of relative micromovements between the zirconia abutment and the titanium alloy of the implant, in a biochemical aggressive environment. Thus, it is important to establish the in vitro tribological testing conditions that better mimics such environment. The present work aims to evaluate the effect of ball-on-plate tests configuration on the tribological behavior of ZrO2/Ti6Al4V pair in dry and lubricated conditions, using different lubricants: water, artificial saliva solution and human saliva. Ceramic balls sliding on metallic plates (TiPlate) and metallic balls sliding on ceramic plates (TiBall) were tested and the coefficient of friction (CoF) and wear response was monitored trough nanotribological tests. Open circuit potential was also measured during the tests carried out in saline solution (artificial saliva) to access the tribochemical response. The wear mechanisms were evaluated by scanning electron microscopy and atomic force microscopy analysis. Relevant differences were found between the two configurations, with and without the presence of human saliva: TiPlate presented always a higher CoF than TiBall, which may have resulted from differences in the degradation and regeneration processes of the titanium passive film during sliding. TiBall demonstrated to be the best choice to reproduce the in vivo conditions, since the metallic surface contacts permanently with zirconia, impairing the titanium repassivation. Regarding the effect of the lubricants, it was observed that human saliva had a protective action of the surfaces, leading to the lowest CoF among the lubricants used (0.19 ±â€¯0.05 for TiBall and 0.35 ±â€¯0.08 for TiPlate) and neglectable wear.

Comparative study of the wear of the pair human teeth/Vita Enamic® vs commonly used dental ceramics through chewing simulation.

Ceramic based prosthetic materials have been used in dental restorations due to their excellent aesthetic and biocompatibility. However, due to concerns related to their mechanical properties and abrasive action against natural teeth, a proper selection of these materials is crucial to preserve the occlusal interactions and prevent abnormal dental wear. The aim of this work is to compare the wear performance of Vita Enamic®, a polymer infiltrated ceramic (PIC), with that of other three commercial ceramic based dental materials - Zirconia, Leucite and Zirconia Veneered - when tested against natural teeth. The crystalline structure, wettability, topography and hardness of the prosthetic materials were characterized before wear testing. Chewing simulator experiments (360,000 cycles, load 49 N) against dental human cusps were carried out using artificial saliva as lubricant. The wear of both teeth and prosthetic materials was quantified and the involved wear mechanisms were analyzed by scanning electron microscopy. The results showed that Zirconia presented the most suitable tribological behavior, since it led to the lowest wear on both occlusal surfaces. The prosthetic material presenting the highest wear was Vita Enamic®. Regarding the cusps' wear, the highest values were found for both Leucite and Zirconia Veneered. Polishing wear was the main wear mechanism in Zirconia system (prosthetic material and opposing enamel), while in the remaining ones was fragile fracture associated with abrasive wear. No direct relation could be established between wettability, initial roughness and hardness of the prosthetic materials and the wear of the tribological systems. Contrarily, microstructure and toughness revealed to be critical parameters.

Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading.

Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac.

Controlled release of moxifloxacin from intraocular lenses modified by Ar plasma-assisted grafting with AMPS or SBMA: An in vitro study.

Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release.

Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect.

In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1799-1807, 2017.

Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion.

Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors EHS, Eel and Ead which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While EHS and Eel are close to 1, Ead>>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, De, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=De×Ead allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling.

Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.

Tribological behaviour of unveneered and veneered lithium disilicate dental material.

The friction and wear behaviour of a lithium disilicate dental ceramic against natural dental enamel is studied, including the effect of the presence of a fluorapatite veneering upon the tribological properties of the material. The tribological behaviour was assessed using reciprocating pin-on-plate test configuration, at pH 3 and pH 7. The surface energy of the plates was determined, as well as the zeta potential of fluorapatite, lithium disilicate and enamel particles in artificial saliva. It was found that the friction and wear behaviour of the tested enamel/plate material tribocouples is less severe in unveneered plates. Initial surface roughness of the plate does not affect wear results. However the topography of the resulting wear track affects the corresponding wear loss: a smoother final wear track is associated with lower wear. The surface topography of the wear track, and thus the tribological performance of the tested materials, is very sensitive to the pH of the sliding solution. This is because the dissolution trend, wettability and surface charge of the used materials are pH dependent. Overall friction and wear are higher under basic pH conditions, especially when plates are veneered. A wear model is proposed that correlates the effect of the described parameters with the observed tribological behaviour at pH 7. Attained results show that fluorapatite coating of lithium disilicate dental crowns affects tooth/crown wear behaviour, resulting in increased wear of both the artificial crown and the opposing natural teeth. Coating should therefore be avoided in occlusal crown surfaces.