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Refereed/Peer-reviewed The ability to create complex three-dimensional cellular models that can effectively replicate the structure and function of human organs and tissues in vitro has the potential to revolutionize medicine. Such models could facilitate the interrogation of developmental and disease processes underpinning fundamental discovery science, vastly accelerate drug development and screening, or even be used to create tissues for implantation into the body. Realization of this potential, however, requires the recreation of complex biochemical, biophysical, and cellular patterns of 3D tissues and remains a key challenge in the field. Recent advances are being driven by improved knowledge of tissue morphogenesis and architecture and technological developments in bioengineering and materials science that can create the multidimensional and dynamic systems required to produce complex tissue microenvironments. In this article, we discuss challenges for in vitro models of tissues and organs and summarize the current state-of-the art in biomaterials and bioengineered systems that aim to address these challenges. This includes both top-down technologies, such as 3D photopatterning, magnetism, acoustic forces, and cell origami, as well as bottom-up patterning using 3D bioprinting, microfluidics, cell sheet technology, or composite scaffolds. We illustrate the varying ways that these can be applied to suit the needs of different tissues and applications by focussing on specific examples of patterning the bone-tendon interface, kidney organoids, and brain cancer models. Finally, we discuss the challenges and future prospects in applying materials science and bioengineering to develop high-quality 3D tissue structures for in vitro studies. Published under an exclusive license by AIP Publishing.

The ability of mesenchymal stem cells to sense nanoscale variations in extracellular matrix (ECM) compositions in their local microenvironment is crucial to their survival and their fate; however, the underlying molecular mechanisms defining how such fates are temporally modulated remain poorly understood. In this work, we have utilized self-assembled block copolymer surfaces to present nanodomains of an adhesive peptide found in many ECM proteins at different lateral spacings (from 30 to 60 nm) and studied the temporal response (2 h to 14 days) of human mesenchymal stem cells (hMSCs) using a panel of real-time localization and activity biosensors. Our findings revealed that within the first 4 to 24 h postadhesion and spreading, hMSCs on smaller nanodomain spacings recruit more activated FAK and Src proteins to produce larger, longer-lived, and increased numbers of focal adhesions (FAs). The adhesions formed on smaller nanospacings rapidly recruit higher amounts of nonmuscle myosin IIA and vinculin and experience tension forces (by >5 pN/FA) significantly higher than those observed on larger nanodomain spacings. The transmission of higher levels of tension into the cytoskeleton at short times was accompanied by higher Rac1, cytosolic β-catenin, and nuclear localization of YAP/TAZ and RUNX2, which together biased the commitment of hMSCs to an osteogenic fate. This investigation provides mechanistic insights to confirm that smaller lateral spacings of adhesive nanodomains alter hMSC mechanosensing and biases mechanotransduction at short times via differential coupling of FAK/Src/Rac1/myosin IIA/YAP/TAZ signaling pathways to support longer-term changes in stem cell differentiation and state Refereed/Peer-reviewed

Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100-5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by demonstrating convergence on mTOR signalling. By modulating these mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The outcomes of this study provide new understanding of the mechanisms regulating MSC mechanotransduction and differentiation, but also a novel strategy with which to drive MSC fate and significantly impact MSC-based tissue-engineering applications., Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.

We introduce “sense, track and separate” approach for the removal of Hg2+ ion from aqueous media using highly ordered and magnetic mesoporous ferrosilicate nanocages functionalised with rhodamine fluorophore derivative. These functionalised materials offer both fluorescent and magnetic properties in a single system which help not only to selectively sense the Hg2+ ions with a high precision but also adsorb and separate a significant amount of Hg2+ ion in aqueous media. We demonstrate that the magnetic affinity of these materials, generated from the ultrafine γ-Fe2O3 nanoparticles present inside the nanochannels of the support, can efficiently be used as a fluorescent tag to sense the Hg2+ ions present in NIH3T3 fibroblasts live cells and to track the movement of the cells by external magnetic field monitored using confocal fluorescence microscopy. This simple approach of introducing multiple functions in the magnetic mesoporous materials raise the prospect of creating new advanced functional materials by fusing organic, inorganic and biomolecules to create advanced hybrid nanoporous materials which have a potential use not only for sensing and the separation of toxic metal ions but also for cell tracking in bio-separation and the drug delivery.