Fused deposition modelling (FDM) is an additive manufacturing technique widely used for rapid prototyping. This method facilitates the creation of parts with intricate geometries, making it suitable for advanced applications in fields such as tissue engineering, aerospace, and electronics. Despite its advantages, FDM often results in the formation of voids between the deposited filaments, which can compromise mechanical properties. However, in some cases, such as the design of scaffolds for bone regeneration, increased porosity can be advantageous as it allows for better permeability. On the other hand, the introduction of nano-additives into the FDM material enhances design flexibility and can significantly improve the mechanical properties. Therefore, modelling FDM-produced components involves complexities at two different scales: nanoscales and microscales. Material deformation is primarily influenced by atomic-scale phenomena, especially with nanoscopic constituents, whereas the distribution of nano-reinforcements and FDM-induced heterogeneities lies at the microscale. This work presents multiscale modelling that bridges the nano and microscales to predict the mechanical properties of FDM-manufactured components. At the nanoscale, molecular dynamic simulations unravel the atomistic intricacies that dictate the behaviour of the base material containing nanoscopic reinforcements. Simulations are conducted on polylactic acid (PLA) and PLA reinforced with silver nanoparticles, with the properties derived from MD simulations transferred to the microscale model. At the microscale, non-classical micropolar theory is utilised, which can account for materials\' heterogeneity through internal scale parameters while avoiding direct discretization. The developed mechanical model offers a comprehensive framework for designing 3D-printed PLA nanocomposites with tailored mechanical properties.

Microneedles (MNs) have emerged as an innovative, virtually painless technique for intradermal drug delivery. However, the complex and costly fabrication process has limited their widespread accessibility, especially for individuals requiring frequent drug administration. This study introduces a groundbreaking and cost-effective method for producing MNs utilizing fused deposition modeling (FDM) 3D printing technology to enhance transdermal drug delivery. The proposed fabrication process involves the elongation of molten polylactic acid (PLA) filaments to create meticulously designed conoid and neiloid MNs with smooth surfaces. This study underscores the critical role of printing parameters, particularly extrusion length and printing speed, in determining the shape of the MNs. Notably, the conoid-shaped MNs exhibit exceptional skin-penetrating capabilities. In order to evaluate their effectiveness, the MNs were tested on a polydimethylsiloxane (PDMS) skin model for skin penetration. The results highlight the high potential of 3D-printed MNs for transdermal drug administration. This novel approach capitalizes on the benefits of 3D printing technology to fabricate MNs that hold the promise of transforming painless drug administration for a variety of medical applications.

The primary focus of the research is to study the role of cocrystal and amorphous solid dispersion approaches for enhancing solubility and preserving the stability of a poorly soluble drug, i.e., ibuprofen (IBP). First, the solvent-assisted grinding approach determined the optimum molar ratio of the drug and the coformer (nicotinamide (NIC)). Later, the polymeric filaments of cocrystals and amorphous solid dispersions were developed using the hot melt extrusion (HME) process, and the printlets were fabricated using the fused deposition modeling (FDM) additive manufacturing process. In addition, the obtained filaments were also milled and compressed into tablets as reference samples. The formation of cocrystals and amorphous solid dispersions was evaluated and confirmed using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD) analysis. The drug release profiles of 3D printlets with 50% infill were found to be faster and are in line with the release profiles of compressed tablets. In addition, the 3D-printed cocrystal formulation was stable for 6 months at accelerated conditions. However, the 3D printlets of amorphous solid dispersions and compressed tablets failed to retain stability attributed to the recrystallization of the drug and loss in tablet mechanical properties. This shows the suitability of a cocrystal platform as a novel approach for developing stable formulations of poorly soluble drug substances over amorphous solid dispersions.

The present work reports on the fabrication of high-density polyethylene sponges, decorated with Mn-doped ZnO nanostructures. The sponges were developed utilizing three-dimensional printing technology, while Mn-doped ZnO nanostructures, with varying doping levels, were grown at mild temperatures. The nanostructures were fully characterized by means of scanning electron microscopy, X-ray diffraction, and Raman spectroscopy, revealing the existence of Mn doping. Moreover, their photocatalytic properties were investigated using the degradation/decolorization of a commercially available liquid laundry detergent, based on synthetic, less foaming ingredients, under UV irradiation. The Mn-doped ZnO nanostructures show better photocatalytic activity at higher doping levels. This study demonstrates that it is possible to achieve the adequate degradation of a typical detergent solution in water by means of low-cost and environmentally friendly approaches, while Mn-doped ZnO/HDPE nanostructures are good candidates for real environmental applications.

This study was conducted on different models of biodegradable SMP (shape-memory polymer) scaffolds. A comparison was conducted utilizing a basic FDM (fused deposition modeling)/MEX (material extrusion) printer with a standard printing technique and a novel, modified, four-axis printing method with a PLA (poly lactic acid) polymer as the printing material. This way of making the 4D-printed BVS (biodegradable vascular stent) made it possible to achieve high-quality surfaces due to the difference in printing directions and improved mechanical properties-tensile testing showed a doubling in the elongation at break when using the four-axis-printed specimen compared to the regular printing, of 8.15 mm and 3.92 mm, respectfully. Furthermore, the supports created using this method exhibited a significant level of shape recovery following thermomechanical programming. In order to test the shape-memory effect, after the thermomechanical programming, two approaches were applied: one approach was to heat up the specimen after unloading it inside temperature chamber, and the other was to heat it in a warm bath. Both approaches led to an average recovery of the original height of 99.7%, while the in-chamber recovery time was longer (120 s) than the warm-bath recovery (~3 s) due to the more direct specimen heating in the latter case. This shows that 4D printing using the newly proposed four-axis printing is an effective, promising technique that can be used in the future to make biodegradable structures from SMP.

Hot-melt extrusion (HME) and subsequent FDM 3D printing offer great potential opportunities in the formulation development and production of customized oral dosage forms with poorly soluble drugs. However, thermal stress within these processes can be challenging for thermo-sensitive drugs. In this work, three different formulations were prepared to investigate the degradation and the solid state of the thermo-sensitive and poorly soluble drug escitalopram oxalate (ESC-OX) during the two heat-intensive processes HME and FDM 3D printing. For this purpose, hydroxypropyl methyl cellulose (HPMC) and basic butylated methacrylate copolymer (bPMMA) were chosen as polymers. DSC and XRD measurements revealed that ESC-OX is amorphous in the HPMC based formulations in both, extrudates and 3D printed tablets. In contrast, in-situ amorphization of the drug from crystalline state in bPMMA filaments was observed during FDM 3D printing. With regard to the content, it was found that degradation of ESC-OX in extrudates with bPMMA could be avoided and in 3D printed tablets almost fully reduced. Furthermore, a possible conversion into the R-enantiomer in the formulation with bPMMA could be excluded using a chiral column. Compared to the commercial product Cipralex®, drug release from extrudates and tablets with bPMMA was slower but still qualified as immediate drug release.

To increase the applications of FDM (fusion deposition modeling) 3D printing in electronics, it is necessary to develop new filaments with good electrical properties and suitable processability. In this work, polymer composites filament-shaped with superior electrical performance based on polylactic acid (PLA) carbon nanotubes and lignin blends have been studied by combining solution mixing and melt blending. The results showed that composites achieve electrical percolation from 5 wt.% of nanotubes, with high electrical conductivity. Moreover, the introduction of a plasticizing additive, lignin, improved the printability of the material while increasing its electrical conductivity (from (1.5 ± 0.9)·10-7 S·cm-1 to (1.4 ± 0.9)·10-1 S cm-1 with 5 wt.% carbon nanotubes and 1 wt.% lignin) maintaining the mechanical properties of composite without additive. To validate lignin performance, its effect on PLA/MWCNT was compare with polyethylene glycol. PEG is a well-known commercial additive, and its use as dispersant and plasticizer in PLA/MWCNT composites has been proven in bibliography. PLA/MWCNT composites display easier processability by 3D printing and more adhesion between the printed layers with lignin than with PEG. In addition, the polyethylene glycol produces a plasticizing effect in the PLA matrix reducing the composite stiffness. Finally, an interactive electronic prototype was 3D printed to assess the printability of the new conducting filaments with 5 wt.% of MWCNT.

In this study, 3D-printed tablets with a constant surface area were designed and fabricated using polylactic acid (PLA) in the outer compartment and polyvinyl alcohol and felodipine (FDP) in the inner compartment. The influences of different surface geometries of the inner compartment, namely, round, hexagon, square, and triangle, on drug release from 3D-printed tablets were also studied. The morphology and porosity of the inner compartment were determined using scanning electron microscopy and synchrotron radiation X-ray tomographic microscopy, respectively. Additionally, drug content and drug release were also evaluated. The results revealed that the round-shaped geometry seemed to have the greatest total surface area of the inner compartment, followed by square-shaped, hexagon-shaped, and triangle-shaped geometries. FDP-loaded 3D-printed tablets with triangle and hexagon surface geometries had the slowest drug release (about 80% within 24 h). In the round-shaped and square-shaped 3D-printed tablets, complete drug release was observed within 12 h. Furthermore, the drug release from triangle-shaped 3D-printed tablets with double the volume of the inner compartment was faster than that of a smaller volume. This was due to the fact that a larger tablet volume increased the surface area contacting the medium, resulting in a faster drug release. The findings indicated that the surface geometry of 3D-printed tablets with a constant surface area affected drug release. This study suggests that 3D printing technology may be used to develop oral solid dosage forms suitable for customized therapeutic treatments.

Three-dimensional (3D) printing, digitalization, and artificial intelligence (AI) are gaining increasing interest in modern medicine. All three aspects are combined in personalized medicine where 3D-printed dosage forms are advantageous because of their variable geometry design. The geometry design can be used to determine the surface area to volume (SA/V) ratio, which affects drug release from the dosage forms. This study investigated artificial neural networks (ANN) to predict suitable geometries for the desired dose and release profile. Filaments with 5% API load and polyvinyl alcohol were 3D printed using Fused Deposition Modeling to provide a wide variety of geometries with different dosages and SA/V ratios. These were dissolved in vitro, and the API release profiles were described mathematically. Using these data, ANN architectures were designed with the goal of predicting a suitable dosage form geometry. Poor accuracies of 68.5% in the training and 44.4% in the test settings were achieved with a classification architecture. However, the SA/V ratio could be predicted accurately with a mean squared error loss of only 0.05. This study shows that the prediction of the SA/V ratio using AI works, but not of the exact geometry. For this purpose, a global database could be built with a range of geometries to simplify the prescription process.

Fused deposition modeling (FDM) 3D printing was used to produce 3D printed tablets with the thermo-sensitive model peptidomimetic drug enalapril maleate (EM). Two different formulations were prepared to investigate the degradation of enalapril maleate during the FDM 3D printing process. Soluplus® and Eudragit® E PO were chosen as polymers. After hot-melt extrusion (HME) and FDM 3D printing, both formulations were characterised regarding their solid-state properties using DSC and XRD. The degradation of the drug was analysed by determination of the content in the extrudates and 3D printed tablets, and dissolution was assessed. Various approaches have been attempted to prevent degradation of enalapril maleate, including utilization of a larger nozzle diameter and higher printing speeds to reduce heat exposition. None of these approaches were successful in preventing drug degradation. However, significant differences in the amount of degradation between the two formulations with different polymers could be observed. Thus, the FDM 3D printing process was not feasible without any degradation for the thermo-sensitive drug enalapril maleate. A maximum of 85.55 ± 1.48% enalapril was recovered in Eudragit® E PO tablets printed with a 0.4 mm nozzle at a temperature of 180 °C and with a speed of 30 mm/s.