Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability.

Bioprinting with cell-laden hydrogels (bioink) requires the careful mixing of cells with the hydrogel carrier to ensure that the bioink is homogeneous and functional, and the printing results are reproducible. Bioink preparation is therefore a critical process step that must accommodate the specific rheological properties of different bioinks. Here, we developed a reproducible method for the optimized mixing of cells and hydrogel carriers that can be integrated into current bioprinting processes. First, we tested and optimized different mixing devices for their effect on bioink homogeneity and rheological properties, resulting in a low-shear process for the preparation of homogenous bioinks. Based on these findings, we evaluated the impact of different cell densities on the rheological profile of bioinks according to shear and temperature, and estimated the impact of shear stress intensity and duration on 1.1B4 cells. Finally, we integrated the optimized mixing method into a current printing process and monitored the printed construct for 14 days to confirm cell viability. We found that the cell viability in the printed cell-laden constructs remained in excess of 91% after 14 days.

Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model substances on the human nail plate and a model membrane from the horse hoof was investigated. A linear correlation was found between drug uptake by the human nail plate and the uptake by the equine hoof. The developed and established permeation device is suitable for investigations of ungual drug transport and enables the use of different membrane diameters and the use of a gel-based nail bed analog. The hydrogel-based acceptor medium used ensures adequate stabilization and hydration of the nail membrane.

Biofabrication methods such as extrusion-based bioprinting allow the manufacture of cell-laden structures for cell therapy, but it is important to provide a sufficient number of embedded cells for the replacement of lost functional tissues. To address this issue, we investigated mass transfer rates across a bioink hydrogel for the essential nutrients glucose and glutamine, their metabolites lactate and ammonia, the electron acceptor oxygen, and the model protein bovine serum albumin. Diffusion coefficients were calculated for these substances at two temperatures. We could confirm that diffusion depends on the molecular volume of the substances if the bioink has a high content of polymers. The analysis of pancreatic 1.1B4 β-cells revealed that the nitrogen source glutamine is a limiting nutrient for homeostasis during cultivation. Taking the consumption rates of 1.1B4 β-cells into account during cultivation, we were able to calculate the cell numbers that can be adequately supplied by the cell culture medium and nutrients in the blood using a model tissue construct. For blood-like conditions, a maximum of ~10⁶ cells·mL⁻¹ was suitable for the cell-laden construct, as a function of the diffused substrate and cell consumption rate for a given geometry. We found that oxygen and glutamine were the limiting nutrients in our model.

A method to quantify fluorescent labels spatially resolved in scattering and absorbing samples is proposed and tested using a tissue phantom. The method works without any a priori knowledge about the optical properties of the sample. The scattering and absorption behavior of the sample is estimated by measuring reflectance from the sample simultaneously to the fluorescence. With this estimation, the attenuation of the fluorescence caused by scattering and absorption can be mathematically compensated. The method is planned to be used for evaluating skin penetrating drug carrier systems.