Three-dimensional bioprinted cancer models: A powerful platform for investigating tunneling nanotube-like cell structures in complex microenvironments.

Bioprinting technology offers layer-by-layer positioning of cells within 3D space with complexity and a defined architecture. Cancer models based in this biofabrication technique are important tools to achieve representative and realistic in vivo conditions of the tumor microenvironment. Here, we show the development of a proof-of-concept three-dimensional bioprinted cancer model that successfully recapitulates the intercellular communication via the assembly of functional tunneling nanotube (TNT)-like cell projections. Different combinations of collagen-containing culture medium, sodium alginate and gelatin were initially prepared and rheologically evaluated. The optimized mixture was used to print two preliminary 3D models for cancer cell seeding. Favourable results in cell viability and proliferation led to the inclusion of 786-O renal cancer cells into the biomaterial mixture to directly bioprint the most suitable 3D model with embedded cells. Bioprinted cells remained viable for at least 15 days of culture and proliferated. More importantly, these cancer cells were able to build TNT-like cellular projections inside the hydrogel that established direct contacts between distant cells. We show that these structures were used as channels for the scrolling and intercellular transfer of mitochondria thus reproducing TNT's function in 2D culture systems. This 3D bioprinted renal cancer model provides a novel alternative tool for studying the functional relevance of TNT-like structures in tumorigenesis and anticancer drug susceptibility in a highly controlled and reproducible tumor microenvironment.

3D printed gummies: Personalized drug dosage in a safe and appealing way.

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics. Four inks were formulated, characterised and 3D printed by means of syringe-based extrusion mechanism. Different tests were performed to ensure reproducibility of the process and validate work methodology for dosage unit fabrication applying basic manufacturing standards. Rheological test helped in evaluating inks printability. Visual characterization concluded that drugmies, apart from a high fidelity in the 3D model shape reproduction, had a bright and uniformly coloured appearance and a pleasant aroma, which made them highly appetising and attractive. The printed gummy oral dosages complied comfortably with the mass uniformity assay regardless of the formulated ink used or the 3D model selected for printing. Ranitidine hydrochloride individual contents were determined using uv-vis spectrophotometry, showing successful results both in dose accuracy, uniformity of drug content and dissolution.