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.

Proton Beam Therapy in the Reirradiation Setting of Brain and Base of Skull Tumour Recurrences.

The therapeutic management of local tumour recurrence after a first course of radical radiotherapy is always complex. Surgery and reirradiation carry increased morbidity due to radiation-induced tissue changes. Proton beam therapy (PBT) might be advantageous in the reirradiation setting, thanks to its distinct physical characteristics. Here we systematically reviewed the use of PBT in the management of recurrent central nervous system (CNS) and base of skull (BoS) tumours, as published in the literature. The research question was framed following the Population, Intervention, Comparison and Outcomes (PICO) criteria: the population of the study was cancer patients with local disease recurrence in the CNS or BoS; the intervention was radiation treatment with PBT; the outcomes of the study focused on the clinical outcomes of PBT in the reirradiation setting of local tumour recurrences of the CNS or BoS. The identification stage resulted in 222 records in Embase and 79 in Medline as of March 2023. Sixty-eight duplicates were excluded at this stage and 56 were excluded after screening as not relevant, not in English or not full-text articles. Twelve full-text articles were included in the review and are presented according to the site of disease, namely BoS, brain or both brain and BoS. This review showed that reirradiation of brain/BoS tumour recurrences with PBT can provide good local control with acceptable toxicity rates. However, reirradiation of tumour recurrences in the CNS or BoS setting needs to consider several factors that can increase the risk of toxicities. Therefore, patient selection is crucial. Randomised evidence is needed to select the best radiation modality in this group of patients.

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.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

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.

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.

Stereotactic Radiosurgery and Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) represent non-invasive, efficacious and safe radiation treatments for the ablation of intracranial and extracranial metastases. Although the use of SRS has been established by level 1 evidence for patients presenting with up to three or four brain metastases for at least a decade, the paradigm of ablating a limited number of extracranial metastases (typically up to five, known as oligometastatic disease) has yet to be proven beyond the few reported but highly encouraging phase II randomised trials. In this overview, we summarise the phase III randomised controlled trials evaluating SRS for intact brain metastases and postoperative surgical cavities and introduce the limited literature and future concepts for treating patients with more than five intracranial metastases. Next, we summarise the published phase II randomised controlled trials specific to SBRT and oligometastatic disease, while briefly describing and contrasting the technical principles and biological mechanisms of SBRT versus conventional radiation. Phase III evidence for SBRT is needed, and we summarise ongoing trials in this overview. Ultimately, SRS and SBRT have become cornerstone therapeutic options for patients with oligometastatic disease and the future is bright for these patients, considering that not so long ago they were considered incurable and relegated to palliation alone.

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.

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.

Primary Mucosal Melanoma of the Stomach.

Considered to be rare, mucosal melanomas are rare type of melanoma that are found on mucosal surfaces and are primary or metastatic in origin. We report a case of a 66-year-old Hispanic female who presented with vague abdominal pain and upon further endoscopic work-up revealed 2 gastric lesions. Endoscopic biopsy results revealed gastric melanoma in the distal lesion. A PET/CT scan indicated it to be suspicious for the primary site of metastasis but was ultimately diagnosed as a benign nevus on biopsy. An extensive clinical exam showed no other probable sites of origin. The patient underwent a subtotal Billroth II gastrectomy and enterostomy tube placement for temporary feeding. Primary melanoma of the stomach is an exceptionally rare occurrence with limited cases that can be accounted for in literature; thus we report this case for review.

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.

Nanoscale triboactivity of functionalized c-Si surfaces by Fe⁺ ion implantation.

In the present work, we present a study of the effect of Fe(+) ion implantation on the tribological response at nanoscale contact lengths of crystalline silicon (c-Si) surfaces. (1 0 0) silicon wafers were implanted with Fe(+) at a fluence of 2 × 10(17) cm(-2), followed by annealing treatments at temperatures of 800 °C and 1000 °C. After microstructural characterization, nanoabrasive wear tests were performed with an atomic force microscope (AFM) using an AFM diamond tip with a stiff steel cantilever that enables the application of loads between 1 µN and 8 µN. After the nanowear tests, the same AFM was used to visualize and measure the worn craters. It was observed that the as-implanted samples present the poorest nanowear response, i.e. the highest wear rate, even higher than that of the unimplanted Si wafers used as a reference. Nevertheless, annealing treatments result in a measurable increase in the nanowear resistance. In this way we show that Fe(+) ion implantation of c-Si, followed by the proper post-heat treatment, results in the formation of FeSi2 nanoprecipitates finely dispersed in a recrystallized matrix. This can be a valuable way of optimizing the nanotribological behavior of silicon.

The effect of albumin and cholesterol on the biotribological behavior of hydrogels for contact lenses.

The irritation/discomfort associated with the use of contact lenses (CLs) is often related to the eyelid-lens friction. Although the use of such devices is widespread, the information about the influence of the lacrimal fluid biomolecules on the tribological behavior of the CLs hydrogels is scarce. In this work, we investigated the effect of the presence of albumin and cholesterol in the lubricant medium, on the frictional response of two model hydrogels for CLs: a hydroxyethylmethacrylate based hydrogel, HEMA/PVP, and a silicone based one, TRIS/NVP/HEMA. Tribological experiments were done in a nanotribometer, in water and in the presence of solutions of those biomolecules. It was observed a significant increase of the friction coefficient (µ) for HEMA/PVP when the lubricant contains cholesterol, and for TRIS/NVP/HEMA when it contains albumin. Solid-state NMR and DSC analysis revealed that HEMA/PVP hydrated in cholesterol solution has a lower amount of free and loosely bound water than the hydrogel hydrated in water. Therefore, a smaller amount of water shall be released into the contact region during the friction tests with cholesterol solution, leading to a thinner film in the contact zone, and consequently to a higher µ. Concerning TRIS/NVP/HEMA, QCM-D studies showed that this hydrogel adsorbs less albumin than HEMA/PVP and that the formed film is more rigid, which can explain the increase of µ. The obtained results contribute to understand the influence of lacrimal fluid composition on the tribological behavior of CLs materials, being relevant for the selection and optimization of these devices. STATEMENT OF SIGNIFICANCE: Understanding the tribological behavior of contact lenses (CLs) materials in contact with the lacrimal fluid and the role of its components is of major importance to optimize the comfort and overall success of these devices. Nevertheless, the available information on this subject in the literature is scarce. In this work, the effect of albumin and cholesterol (two of the main components of the lacrimal fluid) on the frictional response of distinct types of hydrogels suitable for CLs, is compared, for the first time. Significant differences were observed with the two molecules, depending on the material, stressing the need to further study this issue to understand, predict and optimize the in vivo performance of CLs.