The complex interaction of cells with biomaterials (i.e., materiobiology) plays an increasingly pivotal role in the development of novel implants, biomedical devices, and tissue engineering scaffolds to treat diseases, aid in the restoration of bodily functions, construct healthy tissues, or regenerate diseased ones. However, the conventional approaches are incapable of screening the huge amount of potential material parameter combinations to identify the optimal cell responses and involve a combination of serendipity and many series of trial-and-error experiments. For advanced tissue engineering and regenerative medicine, highly efficient and complex bioanalysis platforms are expected to explore the complex interaction of cells with biomaterials using combinatorial approaches that offer desired complex microenvironments during healing, development, and homeostasis. In this review, we first introduce materiobiology and its high-throughput screening (HTS). Then we present an in-depth of the recent progress of 2D/3D HTS platforms (i.e., gradient and microarray) in the principle, preparation, screening for materiobiology, and combination with other advanced technologies. The Compendium for Biomaterial Transcriptomics and high content imaging, computational simulations, and their translation toward commercial and clinical uses are highlighted. In the final section, current challenges and future perspectives are discussed. High-throughput experimentation within the field of materiobiology enables the elucidation of the relationships between biomaterial properties and biological behavior and thereby serves as a potential tool for accelerating the development of high-performance biomaterials.

Topography-driven alterations to single cell stiffness rather than alterations in cell morphology, is the underlying driver for influencing cell biological processes, particularly stem cell differentiation.

Cell-derived matrices (CDMs) are an interesting alternative to conventional sources of extracellular matrices (ECMs) as CDMs mimic the natural ECM composition better and are therefore attractive as a scaffolding material for regulating the functions of stem cells. Previous research on stem cell differentiation has demonstrated that both surface topography and CDMs have a significant influence. However, not much focus has been devoted to elucidating possible synergistic effects of CDMs and topography on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this study, polydimethylsiloxane (PDMS)-based anisotropic topographies (wrinkles) with various topography dimensions were prepared and subsequently combined with native ECMs produced by human fibroblasts that remained on the surface topography after decellularization. The synergistic effect of CDMs combined with topography on osteogenic differentiation of hBM-MSCs was investigated. The results showed that substrates with specific topography dimensions, coated with aligned CDMs, dramatically enhanced the capacity of osteogenesis as investigated using immunofluorescence staining for identifying osteopontin (OPN) and mineralization. Furthermore, the hBM-MSCs on the substrates decorated with CDMs exhibited a higher percentage of (Yes-associated protein) YAP inside the nucleus, stronger cell contractility, and greater formation of focal adhesions, illustrating that enhanced osteogenesis is partly mediated by cellular tension and mechanotransduction following the YAP pathway. Taken together, our findings highlight the importance of ECMs mediating the osteogenic differentiation of stem cells, and the combination of CDMs and topography will be a powerful approach for material-driven osteogenesis.

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Recent studies have revealed that overexpression of long non‑coding RNA (lncRNA) PVT1 is correlated with several types of cancer. However, its role in pancreatic cancer development remains to be clarified. In the present study, we found that PVT1 promoted the growth and the epithelial‑mesenchymal transition (EMT) of pancreatic cancer cells. We first determined that PVT1 was upregulated in pancreatic cancer tissues compared with adjacent normal tissues. Knockdown of PVT1 inhibited viability, adhesion, migration and invasion. Furthermore, PVT1 knockdown reduced the expression of mesenchymal markers including Snail, Slug, β‑catenin, N‑cadherin and vimentin, while it increased epithelial marker expression of E‑cadherin. Finally, knockdown of PVT1 inhibited the TGF‑β/Smad signaling, including p‑Smad2/3 and TGF‑β1 but enhanced the expression of Smad4. In contrast, overexpression of PVT1 reversed the process. These findings revealed that PVT1 acts as an oncogene in pancreatic cancer, possibly through the regulation of EMT via the TGF‑β/Smad pathway and PVT1 may serve as a potential target for diagnostics and therapeutics in pancreatic cancer.

Biophysical factors such as anisotropic topography composed of micro/nanosized structures are important for directing the fate of human bone marrow‐derived mesenchymal stem cells (hBM‐MSCs) and have been applied to neuronal differentiation. Via high‐throughput screening (HTS) methods based on topography gradients, the optimum topography is determined and translated toward a hierarchical architecture designed to mimic the nerve nano/microstructure. The polydimethylsiloxane (PDMS)‐based topography gradient with amplitudes (A) from 541 to 3073 nm and wavelengths (W) between 4 and 30 µm is developed and the fate commitment of MSC toward neuron lineage is investigated. The hierarchical structures, combining nano‐ and microtopography (W0.3/W26 parallel/perpendicular) are fabricated to explore the combined topography effects on neuron differentiation. From the immunofluorescent staining results (Tuj1 and MAP2), the substrate characterized by W: 26 µm; A: 2.9 µm shows highest potential for promoting neurogenesis. Furthermore, the hierarchical features (W0.3/W26 parallel) significantly enhance neural differentiation. The hBM‐MSCs on the hierarchical substrates exhibit a significantly lower percentage of nuclear Yes‐associated protein (YAP)/TAZ and weaker cell contractility indicating that the promoted neurogenesis is mediated by the cell tension and YAP/TAZ pathway. This research provides new insight into designing biomaterials for applications in neural tissue engineering and contributes to the understanding of topography‐mediated neuronal differentiation.

Protein arginine methyltransferase 5 (PRMT5) has been implicated in the development and progression of human cancers. However, few studies reveal its role in epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. In this study, we find that PRMT5 is up-regulated in pancreatic cancer, and promotes proliferation, migration and invasion in pancreatic cancer cells, and promotes tumorigenesis. Silencing PRMT5 induces epithelial marker E-cadherin expression and down-regulates expression of mesenchymal markers including Vimentin, collagen I and β-catenin in PaTu8988 and SW1990 cells, whereas ectopic PRMT5 re-expression partially reverses these changes, indicating that PRMT5 promotes EMT in pancreatic cancer.More importantly, we find that PRMT5 knockdown decreases the phosphorylation level of EGFR at Y1068 and Y1172 and its downstream p-AKT and p-GSK3β, and then results in down-regulation of β-catenin. Expectedly, ectopic PRMT5 re-expression also reverses the above changes. It is suggested that PRMT5 promotes EMT probably via EGFR/AKT/β-catenin pathway. Taken together, our study demonstrates that PRMT5 plays oncogenic roles in the growth of pancreatic cancer cell and provides a potential candidate for pancreatic cancer treatment. K E Y W O R D SAKT, EGFR, epithelial-mesenchymal transition, GSK3β, protein arginine methyltransferase 5, β-catenin

Surface gradients provide a powerful platform to accelerate multiscale design by efficiently studying of material–cell interactions to ultimately enhance function of synthetic clinical biomaterials. Herein, a novel orthogonal double gradient is reported in which surface stiffness and wettability vary independently and continuously in perpendicular directions, providing unique combinations of stiffness and wettability over a broad range (stiffness: 6–89 MPa; water contact angle: 29°–90°). It is found that mesenchymal stem cell behavior is nonlinearly regulated by surface stiffness and wettability. These combined stiffness and wettability properties of a material significantly affect stem cell adhesion, spreading, nucleus size, and vinculin expression. This high‐throughput screening system enables elucidation of the relationships between biointerface properties and biological behavior, and thereby serves a potential tool for accelerating the development of high‐performance biomaterials.