Top-down tissue engineering aims to produce functional tissues using biomaterials as scaffolds, thus providing cues for cell proliferation and differentiation. Conversely, the bottom-up approach aims to precondition cells to form modular tissues units (building-blocks) represented by spheroids. In spheroid culture, adult stem cells are responsible for their extracellular matrix synthesis, re-creating structures at the tissue level. Spheroids from adult stem cells can be considered as organoids, since stem cells recapitulate differentiation pathways and also represent a promising approach for identifying new molecular targets (biomarkers) for diagnosis and therapy. Currently, spheroids can be used for scaffold-free (developmental engineering) or scaffold-based approaches. The scaffold promotes better spatial organization of individual spheroids and provides a defined geometry for their 3D assembly in larger and complex tissues. Furthermore, spheroids exhibit potent angiogenic and vasculogenic capacity and serve as efficient vascularization units in porous scaffolds for bone tissue engineering. An automated combinatorial approach that integrates spheroids into scaffolds is starting to be investigated for macro-scale tissue biofabrication.

Graphical abstract Nanotechnology has the potential to improve the combat against life-threatening conditions. Considering the COVID-19 scenario, and future outbreaks, nanotechnology can play a pivotal role in several steps, ranging from disinfection protocols, manufacture of hospital clothes, to implementation of healthcare settings. Polymeric nanoparticles are colloidal particles with size ranging from 10 to 999 nm, composed of natural or synthetic polymers. The versatility of polymeric-based nanoparticle engineering can provide (i) specificity, (ii) tunable release kinetics, and (iii) multimodal drug composition, making it possible to overcome common limitations encountered during traditional drug development. Consequently, these particles have been widely used as drug delivery systems against several diseases, such as cancer. Due to inherent competitive advantages, polymeric-based nanoparticles hold astonishing potential to counteract the new coronavirus disease (COVID-19). For this reason, in the present study, the latest advancements in polymer-based nanotechnology approaches used to fight against SARS-CoV-2 are compiled and discussed. Moreover, the importance of forefront in vitro technologies — such as 3D bioprinting and organ-on-chip — to evaluate the efficacy of nanotherapeutic agents is also highlighted. Polymeric nanoparticles can be functionalized to enhance its potential as a nanotherapeutic agent. Due to its many advantages, polymeric-based nanoparticles systems are a promising approach against coronavirus disease 2019 (COVID-19).

Stem cell tissue constructs are likely to come into contact with silver-based nanoparticlessuch as silver chloride nanoparticles (AgCl-NPs)used as microbicidals at the implant site or in cosmetics. However, the effect of silver-based nanoparticles on 3D cell cultures with potential for tissue engineering has received little attention. Here, we examined the effect of sub-lethal doses (5, 10 and 25 lg/mL, for 1, 7 and 21 days) of AgCl-NPs produced by 'green' bacterial-based synthesis on spheroid 3D cultures of human adipose tissue stem cells (ASCs). Light microscopy analysis revealed that the shape and diameter of ASC spheroids remained largely unchanged after AgCl-NP treatment. Flow cytometry analysis with 7-AAD and 2 0 ,7 0-dichlorofluorescein diacetate revealed no statistically significant differences in cell death but showed an increase of ROS levels for the untreated group and significant differences for the groups treated with 5 and 10 lg/mL at day 7 (p = 0.0395, p = 0.0266, respectively). Electron microscopy analysis showed limited cell damage in the periphery of AgCl-NP-treated spheroids. However, treatment with AgCl-NP had statistically Letícia E. Charelli and Nathalia Müller have contributed equally to this work.

The mechanical environment of living cells is as critical as chemical signaling.Mechanical stimuli play a pivotal role in organogenesis and tissue homeostasis.Unbalances in mechanotransduction pathways often lead to diseases, such as cancer, cystic fibrosis, and neurodevelopmental disorders. Despite its inherent relevance, there is a lack of proper mechanoresponsive in vitro study systems. In this context, there is an urge to engineer innovative, robust, dynamic, and reliable organotypic technologies to better connect cellular processes to organ-level function and multi-tissue cross-talk. Mechanically active organoid-on-chip has the potential to surpass this challenge. These systems converge microfabrication, microfluidics, biophysics, and tissue engineering fields to emulate key features of living organisms, hence, reducing costs, time, and animal testing. In this review, we intended to present cutting-edge organ-on-chip platforms that integrate biomechanical stimuli as well as novel multicellular culture, such as organoids. We focused on its application in two main fields: precision medicine and drug development. Moreover, we also discussed the state of the art for the development of an engineered model to assess patient-derived tumor organoid metastatic potential.Finally, we highlighted the current drawbacks and emerging opportunities to match the industry needs. We envision the use of mechanoresponsive organotypic-on-chip microdevices as an indispensable tool for precision medicine, drug development, disease modeling, tissue engineering, and developmental biology.

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