Design of Sustainable Aluminium-Based Feedstocks for Composite Extrusion Modelling (CEM).

Additive manufacturing (AM) has become one of the most promising manufacturing techniques in recent years due to the geometric design freedom that this technology offers. The main objective of this study is to explore Composite Extrusion Modelling (CEM) with aluminium as an alternative processing route for aluminium alloys. This process allows for working with pellets that are deposited directly, layer by layer. The aim of the technique is to obtain aluminium alloy samples for industrial applications with high precision, without defects, and which are processed in an environmentally friendly manner. For this purpose, an initial and preliminary study using powder injection moulding (PIM), necessary for the production of samples, has been carried out. The first challenge was the design of a sustainable aluminium-based feedstock. The powder injection moulding technique was used as a first approach to optimise the properties of the feedstock through a combination of water-soluble polymer, polyethyleneglycol (PEG), and cellulose acetate butyrate (CAB) wich produces low CO2 emissions. To do this, a microstructural characterisation was carried out and the critical solid loading and rheological properties of the feedstocks were studied. Furthermore, the debinding conditions and sintering parameters were adjusted in order to obtain samples with the required density for the following processes and with high geometrical accuracy. In the same way, the printing parameters were optimised for proper material deposition.

The Antimicrobial Activity of Micron-Thin Sol-Gel Films Loaded with Linezolid and Cefoxitin for Local Prevention of Orthopedic Prosthesis-Related Infections.

Orthopedic prosthesis-related infections (OPRI) are an essential health concern. OPRI prevention is a priority and a preferred option over dealing with poor prognosis and high-cost treatments. Micron-thin sol-gel films have been noted for a continuous and effective local delivery system. This study aimed to perform a comprehensive in vitro evaluation of a novel hybrid organic-inorganic sol-gel coating developed from a mixture of organopolysiloxanes and organophosphite and loaded with different concentrations of linezolid and/or cefoxitin. The kinetics of degradation and antibiotics release from the coatings were measured. The inhibition of biofilm formation of the coatings against Staphylococcus aureus, S. epidermidis, and Escherichia coli strains was studied, as well as the cell viability and proliferation of MC3T3-E1 osteoblasts. The microbiological assays demonstrated that sol-gel coatings inhibited the biofilm formation of the evaluated Staphylococcus species; however, no inhibition of the E. coli strain was achieved. A synergistic effect of the coating loaded with both antibiotics was observed against S. aureus. The cell studies showed that the sol-gels did not compromise cell viability and proliferation. In conclusion, these coatings represent an innovative therapeutic strategy with potential clinical use to prevent staphylococcal OPRI.

Influence of Addition of Antibiotics on Chemical and Surface Properties of Sol-Gel Coatings.

Infection is one of the most common causes that leads to joint prosthesis failure. In the present work, biodegradable sol-gel coatings were investigated as a promising controlled release of antibiotics for the local prevention of infection in joint prostheses. Accordingly, a sol-gel formulation was designed to be tested as a carrier for 8 different individually loaded antimicrobials. Sols were prepared from a mixture of MAPTMS and TMOS silanes, tris(tri-methylsilyl)phosphite, and the corresponding antimicrobial. In order to study the cross-linking and surface of the coatings, a battery of examinations (Fourier-transform infrared spectroscopy, solid-state 29Si-NMR spectroscopy, thermogravimetric analysis, SEM, EDS, AFM, and water contact angle, thickness, and roughness measurements) were conducted on the formulations loaded with Cefoxitin and Linezolid. A formulation loaded with both antibiotics was also explored. Results showed that the coatings had a microscale roughness attributed to the accumulation of antibiotics and organophosphites in the surface protrusions and that the existence of chemical bonds between antibiotics and the siloxane network was not evidenced.

A New Antifungal-Loaded Sol-Gel Can Prevent Candida albicans Prosthetic Joint Infection.

Fungal PJI is one of the most feared complications after arthroplasty. Although a rare finding, its high associated morbidity and mortality makes it an important object of study. The most frequent species causing fungal PJI is C. albicans. New technology to treat this type of PJI involves organic-inorganic sol-gels loaded with antifungals, as proposed in this study, in which anidulafungin is associated with organophosphates. This study aimed to evaluate the efficacy of an anidulafungin-loaded organic-inorganic sol-gel in preventing prosthetic joint infection (PJI), caused by Candida albicans using an in vivo murine model that evaluates many different variables. Fifty percent (3/6) of mice in the C. albicans-infected, non-coated, chemical-polished (CP)-implant group had positive culture and 100% of the animals in the C. albicans-infected, anidulafungin-loaded, sol-gel coated (CP + A)-implant group had a negative culture (0/6) (p = 0.023). Taking the microbiology and pathology results into account, 54.5% (6/11) of C. albicans-infected CP-implant mice were diagnosed with a PJI, whilst only 9.1% (1/11) of C. albicans-infected CP + A-implant mice were PJI-positive (p = 0.011). No differences were observed between the bone mineral content and bone mineral density of noninfected CP and noninfected CP + A (p = 0.835, and p = 0.181, respectively). No histological or histochemical differences were found in the tissue area occupied by the implant among CP and CP + A. Only 2 of the 6 behavioural variables evaluated exhibited changes during the study: limping and piloerection. In conclusion, the anidulafungin-loaded sol-gel coating showed an excellent antifungal response in vivo and can prevent PJI due to C. albicans in this experimental model.

A Biodegradable Antifungal-Loaded Sol-Gel Coating for the Prevention and Local Treatment of Yeast Prosthetic-Joint Infections.

Fungal prosthetic-joint infections are rare but devastating complications following arthroplasty. These infections are highly recurrent and expose the patient to the development of candidemia, which has high mortality rates. Patients with this condition are often immunocompromised and present several comorbidities, and thus pose a challenge for diagnosis and treatment. The most frequently isolated organisms in these infections are Candida albicans and Candida parapsilosis, pathogens that initiate the infection by developing a biofilm on the implant surface. In this study, a novel hybrid organo-inorganic sol-gel coating was developed from a mixture of organopolysiloxanes and organophosphite, to which different concentrations of fluconazole or anidulafungin were added. Then, the capacity of these coatings to prevent biofilm formation and treat mature biofilms produced by reference and clinical strains of C. albicans and C. Parapsilosis was evaluated. Anidulafungin-loaded sol-gel coatings were more effective in preventing C. albicans biofilm formation, while fluconazole-loaded sol-gel prevented C. parapsilosis biofilm formation more effectively. Treatment with unloaded sol-gel was sufficient to reduce C. albicans biofilms, and the sol-gels loaded with fluconazole or anidulafungin slightly enhanced this effect. In contrast, unloaded coatings stimulated C. parapsilosis biofilm formation, and loading with fluconazole reduced these biofilms by up to 99%. In conclusion, these coatings represent a novel therapeutic approach with potential clinical use to prevent and treat fungal prosthetic-joint infections.

A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections.

The aim of this study was to evaluate the effectiveness of a moxifloxacin-loaded organic-inorganic sol-gel (A50) by locally preventing the catheter-related bloodstream infection (CRBSI) provoked by Staphylococcus epidermidis (S. epidermidis) and the effect resulting from its hydrolytic degradation on coagulation by using a rabbit in-vivo model. A50 coating can completely inhibit growth and would locally prevent CRBSI provoked by S. epidermidis. None of the coagulation blood parameters showed a significant difference constant over time between the control catheter group and the A50-coated catheter group, despite the visible silica release resulting from physiological A50 sol-gel degradation detected in serum at least during the first week. At pathological level, foreign body reaction was present in both of types of catheter, and it was characterized by the presence of macrophages and foreign body giant cell. However, this reaction was different in each group: the A50-coated catheter group showed a higher inflammation with histiocytes, which were forming granuloma-like aggregates with an amorphous crystalline material inside, accompanied by other inflammatory cells such as plasma cells, lymphocytes and mast cells. In conclusion, A50 coating a venous catheter showed excellent bactericidal anti-biofilm response since it completely inhibited S. epidermidis biofilm development and, far from showing procoagulant effects, showed slightly anticoagulant effects.

A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model.

The aim of this study was to evaluate the effect of a moxifloxacin-loaded organic-inorganic sol-gel with different antibiotic concentration in the in vitro biofilm development and treatment against Staphylococcus aureus, S. epidermidis, and Escherichia coli, cytotoxicity and cell proliferation of MC3T3-E1 osteoblasts; and its efficacy in preventing the prosthetic joint infection (PJI) caused by clinical strains of S. aureus and E. coli using an in vivo murine model. Three bacterial strains, S. epidermidis ATCC 35984, S. aureus 15981, and, E. coli ATCC 25922, were used for microbiological studies. Biofilm formation was induced using tryptic-soy supplemented with glucose for 24 h, and then, adhered and planktonic bacteria were estimated using drop plate method and absorbance, respectively. A 24-h-mature biofilm of each species growth in a 96-well plate was treated for 24 h using a MBECTM biofilm Incubator lid with pegs coated with the different types of sol-gel, after incubation, biofilm viability was estimated using alamrBlue. MC3T3-E1 cellular cytotoxicity and proliferation were evaluated using CytoTox 96 Non-Radioactive Cytotoxicity Assay and alamarBlue, respectively. The microbiological studies showed that sol-gel coatings inhibited the biofilm development and treated to a mature biofilm of three evaluated bacterial species. The cell studies showed that the sol-gel both with and without moxifloxacin were non-cytotoxic and that cell proliferation was inversely proportional to the antibiotic concentration containing by sol-gel. In the in vivo study, mice weight increased over time, except in the E. coli-infected group without coating. The most frequent symptoms associated with infection were limping and piloerection; these symptoms were more frequent in infected groups with non-coated implants than infected groups with coated implants. The response of moxifloxacin-loaded sol-gel to infection was either total or completely absent. No differences in bone mineral density were observed between groups with coated and non-coated implants and macrophage presence lightly increased in the bone grown directly in contact with the antibiotic-loaded sol-gel. In conclusion, moxifloxacin-loaded sol-gel coating is capable of preventing PJI caused by both Gram-positive and Gram-negative species.

Biocompatibility and Corrosion Protection Behaviour of Hydroxyapatite Sol-Gel-Derived Coatings on Ti6Al4V Alloy.

The aim of this work was to prepare hydroxyapatite coatings (HAp) by a sol-gel method on Ti6Al4V alloy and to study the bioactivity, biocompatibility and corrosion protection behaviour of these coatings in presence of simulated body fluids (SBFs). Thermogravimetric/Differential Thermal Analyses (TG/DTA) and X-ray Diffraction (XRD) have been applied to obtain information about the phase transformations, mass loss, identification of the phases developed, crystallite size and degree of crystallinity of the obtained HAp powders. Fourier Transformer Infrared Spectroscopy (FTIR) has been utilized for studying the functional groups of the prepared structures. The surface morphology of the resulting HAp coatings was studied by Scanning Electron Microscopy (SEM). The bioactivity was evaluated by soaking the HAp-coatings/Ti6Al4V system in Kokubo's Simulated Body Fluid (SBF) applying Inductively Coupled Plasma (ICP) spectrometry. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and Alamar blue cell viability assays were used to study the biocompatibility. Finally, the corrosion behaviour of HAp-coatings/Ti6Al4V system was researched by means of Electrochemical Impedance Spectroscopy (EIS). The obtained results showed that the prepared powders were nanocrystalline HAp with little deviations from that present in the human bone. All the prepared HAp coatings deposited on Ti6Al4V showed well-behaved biocompatibility, good bioactivity and corrosion protection properties.