A dive into the bath: embedded 3D bioprinting of freeform in vitro models.

Designing functional, vascularized, human scale in vitro models with biomimetic architectures and multiple cell types is a highly promising strategy for both a better understanding of natural tissue/organ development stages to inspire regenerative medicine, and to test novel therapeutics on personalized microphysiological systems. Extrusion-based 3D bioprinting is an effective biofabrication technology to engineer living constructs with predefined geometries and cell patterns. However, bioprinting high-resolution multilayered structures with mechanically weak hydrogel bioinks is challenging. The advent of embedded 3D bioprinting systems in recent years offered new avenues to explore this technology for in vitro modeling. By providing a stable, cell-friendly and perfusable environment to hold the bioink during and after printing, it allows to recapitulate native tissues' architecture and function in a well-controlled manner. Besides enabling freeform bioprinting of constructs with complex spatial organization, support baths can further provide functional housing systems for their long-term in vitro maintenance and screening. This minireview summarizes the recent advances in this field and discuss the enormous potential of embedded 3D bioprinting technologies as alternatives for the automated fabrication of more biomimetic in vitro models.

Caco-2 in vitro model of human gastrointestinal tract for studying the absorption of titanium dioxide and silver nanoparticles from seafood.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in industry as a white pigment (paints, paper industry and toothpastes), photocatalysts (environmental decontamination and photovoltaic cells), inorganic UV filter (sunscreens and personal care products) and as a food additive (E171) and antimicrobial food packaging material. Silver nanoparticles (Ag NPs) are used in photonics, microelectronics, catalysis and medicine due to their catalytic activity, magnetic and optical polarizability, electrical and thermal conductivities and enhanced Raman scattering. They also have antibacterial, antifungal and antiviral activities, as well as anti-inflammatory potential. The huge increase in the use of nano-based products, mainly metallic NPs, implies the presence of nanomaterials in the environment, and hence, the unintentional human ingestion through water or foods (gastrointestinal tract is the main pathway of NPs intake in humans). The presence of TiO2 NPs and Ag NPs in seafood samples was firstly established using an ultrasound assisted enzymatic hydrolysis procedure and sp-ICP-MS analysis. Several clams, cockles, mussels, razor clams, oysters and variegated scallops, which contain TiO2 NPs and Ag NPs, were subjected to an in vitro digestion process simulating human gastrointestinal digestion in the stomach and in the small and large intestine to determine the bioaccessibility of these NPs. Caco-2 cells were selected as model of human intestinal epithelium for transport studies because of the development of membrane transporters that are responsible for the uptake of chemicals. Parameters as transepithelial electrical resistance (TEER) and permeability of Lucifer Yellow were studied for establishing cell monolayer integrity. TiO2 NPs and Ag NPs transport as well as total Ti and Ag concentrations passing through the gastrointestinal epithelial barrier model (0-2 h) were assessed by sp-ICP-MS and ICP-MS in several molluscs.