Serotonergic-based therapies to decrease the impact of moderate to severe psoriasis: translation of fundamental research into industry

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On the progress of hydrogel-based 3D printing: Correlating rheological properties with printing behaviour

Publication . Bom, Sara; Ribeiro, Ricardo; Ribeiro, Helena; Santos, Catarina; Marto, Joana

One of the exciting future directions in the 3D printing field is the development of innovative personalized smart constructions for bio-applications, including drug delivery, namely high-throughput drug screening and customized topical/oral administration of pharmaceuticals, as well as tissue engineering. In this context, hydrogels have emerged as a promising material that, when combined with extrusion 3D printing, allow the creation of soft-material structures with defined spatial locations, that can be printed at room temperature and customized by tuning the geometric design and/or the formulation components. Thus, the efficacy and quality of such vehicles is dependent on formulation, design, and printing process parameters. However, hydrogel inks are often designed and characterized using different methods and this lack of uniformity impairs. Characterization techniques are usually arbitrary and differ among research groups, challenging the inference of possible conclusions on hydrogel behaviour and potential applications. Therefore, to properly analyse the potential of a particular hydrogel ink formulation, we review, for the first time, the most frequently employed characterization procedures, from rheological approaches to printing parameters and settings, and discuss their relevance, limitations and drawbacks, and highlight future perspectives. Overall, to accelerate the development of high-quality 3D constructs, comprehensive characterization protocols for both pre-printing and printing assays should be adopted. Furthermore, their transversal adoption could serve as a boost in terms of quality requirements and regulatory aspects.

2022-03Journal article

Open access

Photosensitization of human skin fibroblasts by vemurafenib promotes pleiotropic effects on membrane-enclosed organelles and apoptosis

Publication . Alpalhão, Miguel; Botequim, David; Ferreira, João; Santus, Rene; Filipe, Paulo

Vemurafenib (VB), a BRAF inhibitor and a first-line treatment for unresectable or metastatic melanoma, is strongly phototoxic towards normal skin cells. Herein, we show that in cultured HS 68 human diploid dermal fibroblasts, low concentrations of VB suffice to promote photosensitization to low doses of UVA (∼ 5 J/cm2), as evidenced by a significant decrease in cell viability. In contrast to data obtained in chemico our results support a role for ROS (reactive oxygen species). Indeed, peroxidation of cellular lipids was observed which could be alleviated by the lipophilic antioxidant BHT (2,6-di-tert-butyl-4-methylphenol). Using in vivo confocal laser scanning microscopy and vital fluorescent probes it was shown at the single cell level that the plasma membrane and lipid-rich organelles, namely mitochondria, endoplasmic reticulum, and lysosomes, as well as actin filaments, were severely damaged by the UVA-induced VB-photosensitization. Finally, we showed that mitochondrial impairment was concurrent with caspase 3/7 activation and cell death by apoptosis.

2023Journal article

Restricted access