Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Xu, Lin; Fang, Jie; Pan, Jiezhou; Qi, Hexu; Yin, Yun; He, Yunxiang; Gan, Xueqi; Li, Yifei; Li, Yu; Guo, Junling

doi:10.1016/j.bioactmat.2024.08.009

Bioactive Materials

2024

DOI: 10.1016/j.bioactmat.2024.08.009

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Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Lin Xu,

Jie Fang,

Jiezhou Pan

et al.

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2024

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Cited by 3 publications

References 69 publications

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Bio‐Inspired Self‐Renewing Implant Surfaces With Sequential Biofunctional Adaptation for Infectious Diabetic Tissue Repair

Cui,

Wen,

Cai

et al. 2024

Adv Funct Materials

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The clinical success of bioinert, tissue‐interfacing metallic implants is greatly jeopardized by complications such as infections, inflammation, and poor regeneration or biointegration, especially concerning diabetics. Implants featuring self‐renewable surfaces that sequentially dictate antibacterial/anti‐inflammatory, immunomodulatory, and pro‐healing/‐regenerative functionalities represent an emerging solution. Herein, fusing triple marine bioinspirations, namely the multilayered interlocked interfaces of mollusk shells, the adhesive/reactive chemistries of mussels, and the self‐renewing, release‐active mucus layers of corals, a self‐adaptive interfacial engineering strategy that imparts self‐renovating surfaces and temporally‐activatable biofunctionalities to various inert biometallic devices is presented. Specifically, sandwich‐like multilayered coatings are in situ constructed, comprising a substrate‐derived micro/nanostructured prelayer, a mussel‐inspired bioadhesive interlayer, and a polyphenol–antibiotic dynamically‐crosslinked therapeutic gel toplayer. The dynamic bonds within the gel allowed pH/reactive oxygen species‐responsive surface degradation, localized release of multifunctional therapeutics, and conditional exposure of cell‐supportive chemical moieties and micro/nanotopographies. Systematic in‐vitro, in‐ovo, and in‐vivo (spanning osseous, subcutaneous, and wound‐closure implantations) studies demonstrated that the functionalized bone implants or wound closure staples possessed adaptive biocompatibility (cyto‐/hemo/‐tissue‐compatibility) and biofunctionalities to combat device‐associated infections and spur diabetic tissue repair. This study underscores the potential of self‐adaptive coating strategies for orchestrating complex (even contradictory) biological functions in addressing challenging medical conditions that require implant intervention.

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Bio‐Inspired Self‐Renewing Implant Surfaces With Sequential Biofunctional Adaptation for Infectious Diabetic Tissue Repair

Cui,

Wen,

Cai

et al. 2024

Adv Funct Materials

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The role and mechanism of NAT10‐mediated ac4C modification in tumor development and progression

Gu,

Zou,

Pan

et al. 2024

MedComm

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RNA modification has emerged as a crucial area of research in epigenetics, significantly influencing tumor biology by regulating RNA metabolism. N‐acetyltransferase 10 (NAT10)‐mediated N4‐acetylcytidine (ac4C) modification, the sole known acetylation in eukaryotic RNA, influences cancer pathogenesis and progression. NAT10 is the only writer of ac4C and catalyzes acetyl transfer on targeted RNA, and ac4C helps to improve the stability and translational efficiency of ac4C‐modified RNA. NAT10 is highly expressed and associated with poor prognosis in pan‐cancers. Based on its molecular mechanism and biological functions, ac4C is a central factor in tumorigenesis, tumor progression, drug resistance, and tumor immune escape. Despite the increasing focus on ac4C, the specific regulatory mechanisms of ac4C in cancer remain elusive. The present review thoroughly analyzes the current knowledge on NAT10‐mediated ac4C modification in cancer, highlighting its broad regulatory influence on targeted gene expression and tumor biology. This review also summarizes the limitations and perspectives of current research on NAT10 and ac4C in cancer, to identify new therapeutic targets and advance cancer treatment strategies.

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Regulation of Osteogenic Differentiation of hBMSCs by the Overlay Angles of Bone Lamellae-like Matrices

Zhang,

Qu,

Luo

et al. 2024

ACS Appl. Mater. Interfaces

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Oriented fibers in bone lamellae are recognized for their contribution to the anisotropic mechanical performance of the cortical bone. While increasing evidence highlights that such oriented fibers also exhibit osteogenic induction to preosteoblasts, little is known about the effect of the overlay angle between lamellae on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In this study, bone lamellae-like fibrous matrices composed of aligned core−shell [core: polycaprolactone (PCL)/type I collagen (Col I) + shell: Col I] nanofibers were seeded with human BMSCs (hBMSCs) and then laid over on each other layer-by-layer (L-b-L) at selected angles (0 or 45°) to form threedimensional (3D) constructs. Upon culture for 7 and 14 days, osteogenic differentiation of hBMSCs and mineralization within the lamellae assembly (LA) were characterized by realtime PCR, Western blot, immunofluorescent staining for osteogenic markers, and alizarin red staining for calcium deposition. Compared to those of random nanofibers (LA-RF) or aligned fibers with the overlay angle of 45°(LA-AF-45), the LA of aligned fibers at a 0°overlay angle (LA-AF-0) exhibited a noticeably higher osteogenic differentiation of hBMSCs, i.e., elevated gene expression of OPN, OCN, and RUNX2 and protein levels of ALP and RUNX2, while promoting mineral deposition as indicated by alizarin red staining and mechanical testing. Further analyses of hBMSCs within LA-AF-0 revealed an increase in both total and phosphorylated integrin β1, which subsequently increased total focal adhesion kinase (FAK), phosphorylated FAK (p-FAK), and phosphorylated extracellular signal kinase ERK1/2 (p-ERK1/2). Inhibition of integrin β1 and ERK1/2 activity effectively reduced the LA-AF-0-induced upregulation of p-FAK and osteogenic markers (OPN, OCN, and RUNX2), confirming the involvement of integrin β1-FAK-ERK1/ 2 signaling. Altogether, the overlay angle of aligned core−shell nanofiber membranes regulates the osteogenic differentiation of hBMSCs via integrin β1-FAK-ERK1/2 signaling, unveiling the effects of anisotropic fibers on bone tissue formation.

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Zinc finger-inspired peptide-metal-phenolic nanointerface enhances bone-implant integration under bacterial infection microenvironment through immune modulation and osteogenesis promotion

Cited by 3 publications

References 69 publications

Bio‐Inspired Self‐Renewing Implant Surfaces With Sequential Biofunctional Adaptation for Infectious Diabetic Tissue Repair

Bio‐Inspired Self‐Renewing Implant Surfaces With Sequential Biofunctional Adaptation for Infectious Diabetic Tissue Repair

The role and mechanism of NAT10‐mediated ac4C modification in tumor development and progression

Regulation of Osteogenic Differentiation of hBMSCs by the Overlay Angles of Bone Lamellae-like Matrices

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