We have investigated whether inkjet printing technology can be extended to print cells of the adult rat central nervous system (CNS), retinal ganglion cells (RGC) and glia, and the effects on survival and growth of these cells in culture, which is an important step in the development of tissue grafts for regenerative medicine, and may aid in the cure of blindness. We observed that RGC and glia can be successfully printed using a piezoelectric printer. Whilst inkjet printing reduced the cell population due to sedimentation within the printing system, imaging of the printhead nozzle, which is the area where the cells experience the greatest shear stress and rate, confirmed that there was no evidence of destruction or even significant distortion of the cells during jet ejection and drop formation. Importantly, the viability of the cells was not affected by the printing process. When we cultured the same number of printed and non-printed RGC/glial cells, there was no significant difference in cell survival and RGC neurite outgrowth. In addition, use of a glial substrate significantly increased RGC neurite outgrowth, and this effect was retained when the cells had been printed. In conclusion, printing of RGC and glia using a piezoelectric printhead does not adversely affect viability and survival/growth of the cells in culture. Importantly, printed glial cells retain their growth-promoting properties when used as a substrate, opening new avenues for printed CNS grafts in regenerative medicine.

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Satellite droplets are unwanted in inkjet printing and various approaches have been suggested for their reduction. Low jetting speeds limit applications of the process. Added surfactants for wetting and conductivity enhancement may help but dynamic surface tension effects may counteract improvements. A higher fluid viscosity delays ligament break-up, but also leads to slower jets, while viscoelasticity reduces satellite formation only in certain cases. We show here that aqueous solutions of PEDOT:PSS (1:2.5 by weight) are strongly shear-thinning. They exhibit low viscosity within the printing nozzle over a wide range of jet speeds, yet rapidly (< 100 µs) recover a higher viscosity at the low shear rates applicable once the jet has formed, which give the benefit of delayed satellite formation. The delay over a 0.8 mm standoff distance can be sufficient to completely suppress satellites, which is significant for many printing applications.

The features rendering orodispersible films (ODFs) patient-centric formulations are widely discussed in the scientific literature. However there is a lack of research studies exploring ODF characteristics with a potential impact on end-user acceptability. The aim of this study was to identify the key ODF characteristics affecting end-user acceptability by developing in vitro test methods for the prediction of ODFs acceptability and correlate these formulation characteristics with the data obtained from a human panel study. Four drug-free single-polymer films were prepared by solvent casting. Solutions of poly(vinyl) alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395 KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop methods were used to assess disintegration time. A human panel of 24 healthy young adults was employed to identify end-user acceptability criteria of the four study film samples. Texture analysis data of ODF tack were not found to be in agreement with the in vivo perceived stickiness in the mouth. However, measurement of the area under the adhesive force curve obtained by DMA correlated with in vivo perceived stickiness data for all samples. The disintegration times obtained by drop method were more comparable to human panel data than the petri dish method. Hence DMA and drop methods proved to be promising methodologies for the prediction of the end-user acceptability. The type and molecular weight of the film-forming polymer had a strong influence on stickiness perception, whereas only polymeric molecular weight influenced perceived disintegration time. The human panel study showed that Participant Reported Outcomes (PROs) for the perceived stickiness in the mouth and disintegration time of test films received significantly different scores between samples, and thus were identified as the key attributes with the potential to affect the end-user acceptability. ODF stickiness and disintegration time should therefore be evaluated at an early stage of the drug product design.