Electroconductive hydrogels and scaffolds have great potential for strain sensing and in tissue engineering. Herein, we designed electroconductive self-healing hydrogels and shaperecoverable scaffolds with injectability, strain/motion-sensing ability, and neural regeneration capacity. The crosslinked network of hydrogels and scaffolds was synthesized and prepared under physiological conditions from N-carboxyethyl chitosan (CEC), a chitosan-modified polypyrrole (DCP) nanoparticle (∼40 nm), and a unique aldehyde-terminated difunctional polyurethane (DFPU) crosslinker. CEC was mixed with DCP by electrostatic interaction and then crosslinked with DFPU through a dynamic Schiff base reaction. Schiff base endowed the hydrogels with self-healing behavior, confirmed by rheological examinations. Shape-recoverable scaffolds were obtained by freeze-drying the hydrogels. These hydrogels and scaffolds showed injectability and conductivity (3− 6 mS/cm), while the scaffolds also exhibited high water absorption and durable elasticity after repeated deformation. The hydrogels and scaffolds promoted the attachment, proliferation, and differentiation of neural stem cells (NSCs). The scaffolds had excellent strain/motion-sensing properties in vitro and ex vivo as well as biodegradability and biocompatibility in vivo. Moreover, the neural regeneration capacity of the conductive hydrogel or the cell-laden conductive hydrogel was demonstrated by the rescue of motor function (∼53 and ∼80% functional recoveries, respectively) in the zebrafish brain injury model. These hydrogels and scaffolds are potential candidates for nerve repair and motion sensing.

During the past 20 years, the MRE11-RAD50-NBS1 complex has become an increasingly important focus in basic and clinical cancer research. One main conceptual step forward was made with the discovery of NBS1 and the understanding of its critical pathophysiological role in Nijmegen breakage syndrome. Major efforts were carried out to define the role in DNA repair of this complex. Recently, basic research has continuously extended our understanding of the complexity of the NBS1 complex. MRE11-RAD50-NBS1 complex can no longer be viewed as having a single role in DNA damage repair since it also serves as a sensor and a mediator in cell cycle checkpoint signaling. Meanwhile, studies have challenged the concept that NBS1 only functions as a tumor suppressor in preserving genome integrity in the nucleus. It may also provide an oncogenic role in the cytoplasm which is associated with the PI3-kinase/AKT-activation pathway. Consistent with this aspect, a growing body of clinical evidence suggests that NBS1 contains a deleterious character that depends on its subcellular localization. This review focuses on recent experimental evidences demonstrating how NBS1 is translocated into the nucleus by an importin KPNA2 which mediates NBS1 subcellular localization and the functions of the NBS1 complex in tumorigenesis.

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Three-dimentional (3D) multicellular aggregates (spheroids), compared to the traditional 2D monolayer cultured cells, are physiologically more similar to the cells in vivo. So far there are various techniques to generate 3D spheroids. Spheroids obtained from different methods have already been applied to regenerative medicine or cancer research. Among the cell spheroids created by different methods, the substrate-derived spheroids and their forming mechanism are unique. This review focuses on the formation of biomaterial substrate-mediated multicellular spheroids and their applications in tissue engineering and tumor models. First, the authors will describe the special chitosan substrate-derived mesenchymal stem cell (MSC) spheroids and their greater regenerative capacities in various tissues. Second, the authors will describe tumor spheroids derived on chitosan and hyaluronan substrates, which serve as a simple in vitro platform to study 3D tumor models or to perform cancer drug screening. Finally, the authors will mention the self-assembly process for substrate-derived multiple cell spheroids (co-spheroids), which may recapitulate the heterotypic cell-cell interaction for co-cultured cells or crosstalk between different types of cells. These unique multicellular mono-spheroids or co-spheroids represent a category of 3D cell culture with advantages of biomimetic cell-cell interaction, better functionalities, and imaging possibilities.