Innovative Design of a 3D Printed Esophageal Stent Inspired by Nature: Mitigating Migration Challenges in Palliative Esophageal Cancer Therapy.

Esophageal cancer is a complex and challenging tumor to treat, with esophageal stenting being used as a palliative measure to improve the quality of life of patients. Self-expandable metal stents (SEMS), self-expandable plastic stents (SEPS), and biodegradable stents are the most commonly used types of stents. However, complications can arise, such as migration, bleeding, and perforation. To address issues of migration, this study developed a novel 3D printed bioinspired esophageal stent utilizing a highly flexible and ductile TPU material. The stent was designed to be self-expanding and tubular with flared ends to provide secure anchorage at both the proximal and distal ends of the structure. Suction cups were strategically placed around the shaft of the stent to prevent migration. The stent was evaluated through compression-recovery, self-expansion, and anti-migration tests to evaluate its recovery properties, self-expansion ability, and anchoring ability, respectively. The results indicated that the novel stent was able to recover its shape, expand, keep the esophagus open, and resist migration, demonstrating its potential for further research and clinical applications. Finite element analysis (FEA) was leveraged to analyze the stent's mechanical behavior, providing insights into its structural integrity, self-expansion capability, and resistance against migration. These results, supported by FEA, highlight the potential of this innovative stent for further research and its eventual application in preclinical settings.

Evaluation of 3D-Printed Solid Microneedles Coated with Electrosprayed Polymeric Nanoparticles for Simultaneous Delivery of Rivastigmine and N-Acetyl Cysteine.

In the current study, coated microneedle arrays were fabricated by means of digital light processing (DLP) printing. Three different shapes were designed, printed, and coated with PLGA particles containing two different actives. Rivastigmine (RIV) and N-acetyl-cysteine (NAC) were coformulated via electrohydrodynamic atomization (EHDA), and they were incorporated into the PLGA particles. The two actives are administered as a combined therapy for Alzheimer's disease. The printed arrays were evaluated regarding their ability to penetrate skin and their mechanical properties. Optical microscopy and scanning electron microscopy (SEM) were employed to further characterize the microneedle structure. Confocal laser microscopy studies were conducted to construct 3D imaging of the coating and to simulate the diffusion of the particles through artificial skin samples. Permeation studies were performed to investigate the transport of the drugs across human skin ex vivo. Subsequently, a series of tape strippings were performed in an attempt to examine the deposition of the APIs on and within the skin. Light microscopy and histological studies revealed no drastic effects on the membrane integrity of the stratum corneum. Finally, the cytocompatibility of the microneedles and their precursors was evaluated by measuring cell viability (MTT assay and live/dead staining) and membrane damages followed by LDH release.

Effect of Monomer Type on the Synthesis and Properties of Poly(Ethylene Furanoate).

This work aimed to produce bio-based poly(ethylene furanoate) (PEF) with a high molecular weight using 2,5-furan dicarboxylic acid (FDCA) or its derivative dimethyl 2,5-furan dicarboxylate (DMFD), targeting food packaging applications. The effect of monomer type, molar ratios, catalyst, polycondensation time, and temperature on synthesized samples' intrinsic viscosities and color intensity was evaluated. It was found that FDCA is more effective than DMFD in producing PEF with higher molecular weight. A sum of complementary techniques was employed to study the structure-properties relationships of the prepared PEF samples, both in amorphous and semicrystalline states. The amorphous samples exhibited an increase in glass transition temperature of 82-87 °C, and annealed samples displayed a decrease in crystallinity with increasing intrinsic viscosity, as analyzed by differential scanning calorimetry and X-ray diffraction. Dielectric spectroscopy showed moderate local and segmental dynamics and high ionic conductivity for the 2,5-FDCA-based samples. The spherulite size and nuclei density of samples improved with increased melt crystallization and viscosity, respectively. The hydrophilicity and oxygen permeability of the samples were reduced with increased rigidity and molecular weight. The nanoindentation test showed that the hardness and elastic modulus of amorphous and annealed samples is higher at low viscosities due to high intermolecular interactions and degree of crystallinity.

Development of biodegradable customized tibial scaffold with advanced architected materials utilizing additive manufacturing.

In the last decade, the development of customized biodegradable scaffolds and implants has attracted increased scientific interest due to the fact that additive manufacturing technologies allow for the rapid production of implants with high geometric complexity constructed via commercial biodegradable polymers. In this study, innovative designs of tibial scaffold in form of bone-brick configuration were developed to fill the bone gap utilizing advanced architected materials and bio-inspired diffusion canals. The architected materials and canals provide high porosity, as well as a high surface area to volume ratio in the scaffold facilitating that way in the tissue regeneration process and in withstanding the applied external loads. The cellular structures applied in this work were the Schwarz Diamond (SD) and a hybrid SD&FCC hybrid cellular material, which is a completely new architected material that derived from the combination of SD and Face Centered Cubic (FCC) structures. These designs were additively manufactured utilizing two biodegradable materials namely Polylactic acid (PLA) and Polycaprolactone (PCL), using the Fused Filament Fabrication (FFF) technique, in order to avoid the surgery, for the scaffold's removal after the bone regeneration. Furthermore, the additively manufactured scaffolds were examined in terms of compatibility and assembly with the bone's physical model, as well as, in terms of mechanical behavior under realistic static loads. In addition, non-linear finite element models (FEMs) were developed based on the experimental data to accurately simulate the mechanical response of the examined scaffolds. The Finite Element Analysis (FEA) results were compared with the experimental response and afterwards the stress concentration regions were observed and identified. Τhe proposed design of scaffold with SD&FCC lattice structure made of PLA material with a relative density of 20% revealed the best overall performance, showing that it is the most suitable candidate for further investigation (in-vivo test, clinical trials, etc.) and commercialization.

Synthesis of Poly(ethylene furanoate) Based Nanocomposites by In Situ Polymerization with Enhanced Antibacterial Properties for Food Packaging Applications.

Poly(ethylene 2,5-furandicarboxylate) (PEF)-based nanocomposites containing Ce-bioglass, ZnO, and ZrO2 nanoparticles were synthesized via in situ polymerization, targeting food packaging applications. The nanocomposites were thoroughly characterized, combining a range of techniques. The successful polymerization was confirmed using attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy, and the molecular weight values were determined indirectly by applying intrinsic viscosity measurements. The nanocomposites' structure was investigated by depth profiling using time-of-flight secondary ion mass spectrometry (ToF-SIMS), while color measurements showed a low-to-moderate increase in the color concentration of all the nanocomposites compared to neat PEF. The thermal properties and crystallinity behavior of the synthesized materials were also examined. The neat PEF and PEF-based nanocomposites show a crystalline fraction of 0-5%, and annealed samples of both PEF and PEF-based nanocomposites exhibit a crystallinity above 20%. Furthermore, scanning electron microscopy (SEM) micrographs revealed that active agent nanoparticles are well dispersed in the PEF matrix. Contact angle measurements showed that incorporating nanoparticles into the PEF matrix significantly reduces the wetting angle due to increased roughness and introduction of the polar -OH groups. Antimicrobial studies indicated a significant increase in inhibition of bacterial strains of about 9-22% for Gram-positive bacterial strains and 5-16% for Gram-negative bacterial strains in PEF nanocomposite films, respectively. Finally, nanoindentation tests showed that the ZnO-based nanocomposite exhibits improved hardness and elastic modulus values compared to neat PEF.

Graphene Nanoplatelets' Effect on the Crystallization, Glass Transition, and Nanomechanical Behavior of Poly(ethylene 2,5-furandicarboxylate) Nanocomposites.

Poly(ethylene 2,5-furandicarboxylate) (PEF) nanocomposites reinforced with various content of graphene nanoplatelets (GNPs) were synthesized in situ in this work. PEF is a widely known biobased polyester with promising physical properties and is considered as the sustainable counterpart of PET. Despite its exceptional gas barrier and mechanical properties, PEF presents with a low crystallization rate. In this context, a small number of GNPs were incorporated into the material to facilitate the nucleation and overall crystallization of the matrix. Kinetic analysis of both the cold and melt crystallization processes of the prepared materials was achieved by means of differential scanning calorimetry (DSC). The prepared materials' isothermal crystallization from the glass and melt states was studied using the Avrami and Hoffman-Lauritzen theories. The Dobreva method was applied for the non-isothermal DSC measurements to calculate the nucleation efficiency of the GNPs on the PEF matrix. Furthermore, Vyazovkin's isoconversional method was employed to estimate the effective activation energy values of the amorphous materials' glass transition. Finally, the nanomechanical properties of the amorphous and semicrystalline PEF materials were evaluated via nanoindentation measurements. It is shown that the GNPs facilitate the crystallization process through heterogeneous nucleation and, at the same time, improve the nanomechanical behavior of PEF, with the semicrystalline samples presenting with the larger enhancements.

Development of Water-Soluble Electrospun Fibers for the Oral Delivery of Cannabinoids.

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.

Electrospinning/electrospraying coatings for metal microneedles: A design of experiments (DOE) and quality by design (QbD) approach.

The research presented here shows QbD implementation for the optimisation of the key process parameters in electrohydrodynamic atomisation (EHDA). Here, the electrosprayed nanoparticles and electrospun fibers consisting of a polymeric matrix and dye. Eight formulations were assessed consisting of 5% w/v of polycaprolactone (PCL) in dichloromethane (DCM) and 5% w/v polyvinylpyrrolidone (PVP) in ethanol. A full factorial DOE was used to assess the various parameters (applied voltage, deposition distance, flow rate). Further particle and fiber analysis using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Fourier Transform Infrared Spectroscopy (FTIR), particle/fiber size distribution. In addition to this in vitro release studied were carried out using fluorescein and Rhodamine B as model dyes and in vitro permeation studies were applied. The results show a significant difference in the morphology of resultant structures as well as a more rapid release profile for the PVP particles and fibers in comparison to the sustained release profiles found with PCL. In vitro drug release studies showed 100% drug release after 7 days for PCL particles and showed 100% drug release within 120 min for PVP particles. The release kinetics and the permeation study showed that the MN successfully pierced the membrane and the electrospun MN coating released a large amount of the loaded drug within 6 h. This study has demonstrated the capability of these robust MNs to encapsulate a diverse range drugs within a polymeric matrix giving rise to the potential of developed personalised medical devices.