Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.
Biostable electronic materials that can maintain their super mechanical and conductive properties, even when exposed to biofluids, are the fundamental basis for designing reliable bioelectronic devices. Herein, cellulose-derived conductive 2D bio-nanosheets as electronic base materials are developed and assembled into a conductive hydrogel with ultra-high biostability, capable of surviving in harsh physiological environments. The bio-nanosheets are synthesized by guiding the in situ regeneration of cellulose crystal into a 2D planar structure using the polydopamine-reduced-graphene oxide as supporting templates. The nanosheet-assembled hydrogel exhibits stable electrical and mechanical performances after undergoing aqueous immersion and in vivo implantation. Thus, the hydrogel-based bioelectronic devices are able to conformally integrate with the human body and stably record electrophysiological signals. Owing to its tissue affinity, the hydrogel further serves as an "E-skin," which employs electrotherapy to aid in the faster healing of chronic wounds in diabetic mice through transcutaneous electrical stimulation. The nanosheet-assembled biostable, conductive, flexible, and cell/tissue affinitive hydrogel lays a foundation for designing electronically and mechanically reliable bioelectronic devices.
Electrical therapy has attracted significant attention because it can modulate cell behaviors and accelerate tissue repair. However, the effectiveness of electrical therapy is limited. This work develops electroresponsive and conductive polydopaminepolypyrrole microcapsules (PDA-PPy-MCs) on titanium surfaces using electrochemical deposition. During the electrochemical process, PDA and dexamethasone (DEX) as the anion are doped into a PPy backbone to neutralize its positive charge. PDA-PPy-MCs possess the cell affinity of PDA, the microstructure of MCs and the electroresponsive capability of PPy. The incorporation of PDA promotes the conductivity and adhesive strength of PPy. PDA-PPy-MCs can respond to electrical signals to release DEX on demand because of the redox behavior of PPy. The microstructure and PDA improve the drug-loading capability of PDA-PPy-MCs. A high-throughput bone marrow stromal cell (BMSC) culture system is designed to study the synergistic effects of composition, microstructure and electrical stimulation on cell behavior. The results indicate that PDA and the microporous structure not only enhance the biocompatibility of PDA-PPy-MC but also strengthen the effect of electrical stimulation. In vivo implantation shows that PDA-PPy-MCs have good biocompatibility. The high cell affinity, microstructure, conductivity and ability to control drug delivery using electrical signals make PDA-PPy-MCs a promising candidate for an on-demand drug delivery and electrical therapy system.
BackgroundMalignant glioma is the most common primary brain tumor in adults and has a poor prognosis. However, there are no effective targeted therapies for glioma patients. Thus, the development of novel targeted therapeutics for glioma is urgently needed.MethodsIn this study, we examined the prognostic significance BTK expression in patients with glioma. Furthermore, we investigated the mechanism and therapeutic potential of ibrutinib in the treatment of human glioma in vitro and in vivo.ResultsOur data demonstrate that high expression of BTK is a novel prognostic marker for poor survival in patients with glioma. BTK-specific inhibitor ibrutinib effectively inhibits the proliferation, migration and invasion ability of glioma cells. Furthermore, ibrutinib can induce G1 cell-cycle arrest by regulating multiple cell cycle-associated proteins. More importantly, we found that BTK inhibition significantly blocks the degradation of IκBα and prevents the nuclear accumulation of NF-κB p65 subunit induced by EGF in glioma cells.ConclusionsTaken together, our study suggests that BTK is a novel prognostic marker and molecular therapeutic target for glioma. BTK is required for EGFR-induced NF-κB activation in glioma cells. These findings provide the basis for future clinical studies of ibrutinib for the treatment of glioma.
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