Artificial tumor matrices and bioengineered tools for tumoroid generation.

The tumor microenvironment (TME) is critical for tumor growth and metastasis. The TME contains cancer-associated cells, tumor matrix, and tumor secretory factors. The fabrication of artificial tumors, so-called tumoroids, is of great significance for the understanding of tumorigenesis and clinical cancer therapy. The assembly of multiple tumor cells and matrix components through interdisciplinary techniques is necessary for the preparation of various tumoroids. This article discusses current methods for constructing tumoroids (tumor tissue slices and tumor cell co-culture) for pre-clinical use. This article focuses on the artificial matrix materials (natural and synthetic materials) and biofabrication techniques (cell assembly, bioengineered tools, bioprinting, and microfluidic devices) used in tumoroids. This article also points out the shortcomings of current tumoroids and potential solutions. This article aims to promotes the next-generation tumoroids and the potential of them in basic research and clinical application.

Programming Colloidal Self-Assembled Patterns (cSAPs) into Thermo-Responsible Hybrid Surfaces for Controlling Human Stem Cells and Macrophages.

Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1ß) and M2 genes (i.e., TGF-ß and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.