Engineered conductive scaffolds toward neural regeneration should have the ability to regulate mesenchymal stems cell (MSC) differentiation into neural lineage through an electrical stimulation-assisted culture process. In this work, a self-powered electrical stimulation-assisted neural differentiation system for MSCs was realized by combining a high effective triboelectric nanogenerator (TENG) to supply pulsed electric simulation signals and a poly(3,4-ethylenedioxythiophene) (PEDOT)-reduced graphene oxide (rGO) hybrid microfiber (80 μm in diameter) as a scaffold. The conductive PEDOT endows the rGO-PEDOT hybrid microfiber with an enhanced electrical conductivity and maintains a good cytocompatibility. MSCs cultured on this highly conductive rGO-PEDOT hybrid microfiber possess enhanced proliferation ability and good neural differentiation tendency. Importantly, by inducing electric pulses generated by the TENG as the electrical stimulation signal, which are triggered by human walking steps, neural differentiation of MSCs is dramatically improved. This study illustrates the customizability of the rGO-PEDOT hybrid microfiber for neural tissue engineering scaffolding applications, underlines the potential of a self-powered TENG electrical stimulation system for accelerating MSC differentiation into neural cells without bio/chemical cues, and suggests the TENG's practical use as a wearable stimulation system to assist nerve regeneration for a walking person.
Phase‐change materials (PCMs) have emerged as a novel class of thermo‐responsive materials for controlled release, where the payloads encapsulated in a solid matrix are released only upon melting the PCM to trigger a solid‐to‐liquid phase transition. Herein, the advances over the past 10 years in utilizing PCMs as a versatile platform for the encapsulation and release of various types of therapeutic agents and biological effectors are highlighted. A brief introduction to PCMs in the context of desired properties for controlled release and related applications is provided. Among the various types of PCMs, a specific focus is placed on fatty acids and fatty alcohols for their natural availability, low toxicity, biodegradability, diversity, high abundance, and low cost. Then, various methods capable of processing PCMs, and their mixtures with payloads, into stable suspensions of colloidal particles, and the different means for triggering the solid‐to‐liquid phase transition are discussed. Finally, a range of applications enabled by the controlled release system based on PCMs are presented together with some perspectives on future directions.
Background Gliomas are the most common malignant primary brain tumours with a highly immunosuppressive tumour microenvironment (TME) and poor prognosis. Circular RNAs (circRNA), a newly found type of endogenous noncoding RNA, characterized by high stability, abundance, conservation, have been shown to play an important role in the pathophysiological processes and TME remodelling of various tumours. Methods CircRNA sequencing analysis was performed to explore circRNA expression profiles in normal and glioma tissues. The biological function of a novel circRNA, namely, circNEIL3, in glioma development was confirmed both in vitro and in vivo. Mechanistically, RNA pull-down, mass spectrum, RNA immunoprecipitation (RIP), luciferase reporter, and co-immunoprecipitation assays were conducted. Results We identified circNEIL3, which could be cyclized by EWS RNA-binding protein 1(EWSR1), to be upregulated in glioma tissues and to correlate positively with glioma malignant progression. Functionally, we confirmed that circNEIL3 promotes tumorigenesis and carcinogenic progression of glioma in vitro and in vivo. Mechanistically, circNEIL3 stabilizes IGF2BP3 (insulin-like growth factor 2 mRNA binding protein 3) protein, a known oncogenic protein, by preventing HECTD4-mediated ubiquitination. Moreover, circNEIL3 overexpression glioma cells drives macrophage infiltration into the tumour microenvironment (TME). Finally, circNEIL3 is packaged into exosomes by hnRNPA2B1 and transmitted to infiltrated tumour associated macrophages (TAMs), enabling them to acquire immunosuppressive properties by stabilizing IGF2BP3 and in turn promoting glioma progression. Conclusions This work reveals that circNEIL3 plays a nonnegligible multifaceted role in promoting gliomagenesis, malignant progression and macrophage tumour-promoting phenotypes polarization, highlighting that circNEIL3 is a potential prognostic biomarker and therapeutic target in glioma.
The cell-material interface is one of the most important considerations in designing a high-performance tissue engineering scaffold because the surface of the scaffold can determine the fate of stem cells. A conductive surface is required for a scaffold to direct stem cells toward neural differentiation. However, most conductive polymers are toxic and not amenable to biological degradation, which restricts the design of neural tissue engineering scaffolds. In this study, we used a bioactive three-dimensional (3D) porcine acellular dermal matrix (PADM), which is mainly composed of type I collagen, as a basic material and successfully assembled a layer of reduced graphene oxide (rGO) nanosheets on the surface of the PADM channels to obtain a porous 3D, biodegradable, conductive and biocompatible PADM-rGO hybrid neural tissue engineering scaffold. Compared with the PADM scaffold, assembling the rGO into the scaffold did not induce a significant change in the microstructure but endowed the PADM-rGO hybrid scaffold with good conductivity. A comparison of the neural differentiation of rat bone-marrow-derived mesenchymal stem cells (MSCs) was performed by culturing the MSCs on PADM and PADM-rGO scaffolds in neuronal culture medium, followed by the determination of gene expression and immunofluorescence staining. The results of both the gene expression and protein level assessments suggest that the rGO-assembled PADM scaffold may promote the differentiation of MSCs into neuronal cells with higher protein and gene expression levels after 7 days under neural differentiation conditions. This study demonstrated that the PADM-rGO hybrid scaffold is a promising scaffold for neural tissue engineering; this scaffold can not only support the growth of MSCs at a high proliferation rate but also enhance the differentiation of MSCs into neural cells.
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