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Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not enough biomaterial and antibiotic combinations available for personalized implant sizes for patients. The aim of this study was to develop a bone fixation plate coating made of a composite of poly-ε-caprolactone, hydroxyapatite and halloysite nanotubes loaded with gentamicin sulphate and fabricated via fused filament fabrication 3D printing technology. The mechanical and thermal properties of the biomaterial were analyzed. The in vitro release kinetics of gentamicin sulphate were evaluated for 14 days showing a burst release during the first two days that was followed by a sustained release of bactericidal concentrations. The composite loaded with 2 and 5% gentamicin sulphate exhibited complete antimicrobial killing of Staphylococcus aureus in an ex vivo mouse femur fixation plate infection model. Moreover, a fixation plate of the composite loaded with 5% of gentamicin sulphate was able to prevent S. aureus infection in the bone and surrounding tissue in an in vivo mouse bone fixation plate infection model 3 days post-surgery. In conclusion, the newly developed composite material successfully prevented infection in vivo. Additionally, the ability to use fused filament fabrication 3D printing to produce patient-specific implants may provide a wider range of personalized solutions for patients. [ABSTRACT FROM AUTHOR]

Additive manufacturing technologies have been widely used in the medical field. More specifically, fused filament fabrication (FFF) 3D-printing technology has been thoroughly investigated to produce drug delivery systems. Recently, few researchers have explored the possibility of directly 3D printing such systems without the need for producing a filament which is usually the feedstock material for the printer. This was possible via direct feeding of a mixture consisting of the carrier polymer and the required drug. However, as this direct feeding approach shows limited homogenizing abilities, it is vital to investigate the effect of the pre-mixing step on the quality of the 3D printed products. Our study investigates the two commonly used mixing approaches—solvent casting and powder mixing. For this purpose, polycaprolactone (PCL) was used as the main polymer under investigation and gentamicin sulfate (GS) was selected as a reference. The produced systems' efficacy was investigated for bacterial and biofilm prevention. Our data show that the solvent casting approach offers improved drug distribution within the polymeric matrix, as was observed from micro-computed topography and scanning electron microscopy visualization. Moreover, this approach shows a higher drug release rate and thus improved antibacterial efficacy. However, there were no differences among the tested approaches in terms of thermal and mechanical properties. [ABSTRACT FROM AUTHOR]

Fused filament fabrication (FFF) 3D printing technology is widely used in many fields. For almost a decade, medical researchers have been exploring the potential use of this technology for improving the healthcare sector. Advances in personalized medicine have been more achievable due to the applicability of producing drug delivery devices, which are explicitly designed based on patients' needs. For the production of these devices, a filament—which is the feedstock for the FFF 3D printer—consists of a carrier polymer (or polymers) and a loaded active pharmaceutical ingredient (API). This systematic review of the literature investigates the most widely used approaches for producing drug-loaded filaments. It also focusses on several factors, such as the polymeric carrier and the drug, loading capacity and homogeneity, processing conditions, and the intended applications. This review concludes that the filament preparation method has a significant effect on both the drug homogeneity within the polymeric carrier and drug loading efficiency. [ABSTRACT FROM AUTHOR]

[Display omitted] • The mechanical and rheological properties are limiting steps for FFF. • Increasing the VA content showed lower buckling stress, elastic and flexural modulus. • The inadequate flow during FFF was due to the viscosity variation during extrusion. • DEAM showed formulation freedom as the screw rotation drives the material flow. • In-vitro kinetics was similar between tablets printed from filaments, pellets or powder. Personalized medicine, produced through 3D printing, is a promising approach for delivering the required drug dose based on the patient's profile. The primary purpose of this study was to investigate the potential of two different extrusion-based additive manufacturing techniques – fused filament fabrication (FFF) and screw-based 3D printing, also known as direct extrusion additive manufacturing (DEAM). Different ethylene-vinyl acetate (EVA) copolymers (9 %VA, 12 %VA, 16 %VA, 18 %VA, 25 %VA, 28 %VA, and 40 %VA) were selected and loaded with 50% (w/w) metoprolol tartrate (MPT). Hot-melt extrusion was performed to produce the drug-loaded filaments. These filaments were used for FFF in which the mechanical and rheological properties were rate-limiting steps. The drug-loaded filament based on the 18 %VA polymer was the only printable formulation due to its appropriate mechanical and rheological properties. As for the highest VA content (40 %VA), the feeding pinch rolls cause buckling of the filaments due to insufficient stiffness, while other filaments were successfully feedable towards the extrusion nozzle. However, poor flowability out of the extrusion nozzle due to the rheological limitation excluded these formulations from the initial printing trials. Filaments were also pelletized and used for pellets-DEAM. This method showed freedom in formulation selection because the screw rotation drives the material flow with less dependence on their mechanical properties. All drug-loaded pellets were successfully printed via DEAM, as sufficient pressure was built up towards the nozzle due to single screw extrusion processing method. In contrast, filaments were used as a piston to build up the pressure required for extrusion in filament-based printing, which highly depends on the filament's mechanical properties. Moreover, printing trials using a physical mixture in powder form were also investigated and showed promising results. In vitro drug release showed similar release patterns for MPT-loaded 3D printed tablets regardless of the printing technique. Additionally, pellets-DEAM enabled the production of tablets with the highest VA content, which failed in FFF 3D printing but showed an interesting delayed release profile. [ABSTRACT FROM AUTHOR]