Osteoblastic ferroptosis inhibition by small-molecule promoting GPX4 activation for peri-prosthetic osteolysis therapy DOI Creative Commons
Xin Liu, Wei Wang, Feng Zhu

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

Peri-prosthesis osteolysis (PPO) represents the most severe complication of total joint arthroplasty (TJA) surgery and imposes primary cause prosthesis failure subsequent revision surgery. Antiresorptive therapies are usually prescribed to treat PPO, especially for elderly people. Nevertheless, efficacy anti-osteoporotic medications remains constrained. Recent therapeutic strategies promote periprosthetic osseointegration by restoring osteoblast function considered more effective approaches. However, precise mechanism underlying inhibition osteogenesis triggered wear particles enigmatic. Herein, we demonstrate that inhibit inducing ferroptosis sabotage extracellular mineralization arouse osteolysis. The suppression could significantly rescue thus alleviating PPO. Furthermore, Glutathione Peroxidase 4 (GPX4) has been identified as a key target in regulating osteoblastic ferroptosis. By utilizing virtual screening techniques, have successfully conducted comprehensive natural compound known Urolithin A (UA), which exhibits remarkable while simultaneously promoting process through its targeting on GPX4. Meanwhile, UA improves osteolytic conditions vivo even when adjunction titanium (Ti) nanoparticles. This strategy great potential treating peri-prosthesis potentially broadens scope clinical therapy.

Language: Английский

Tracing Immunological Interaction in Trimethylamine N‐Oxide Hydrogel‐Derived Zwitterionic Microenvironment During Promoted Diabetic Wound Regeneration DOI
Zheng Li, Longwei Li, Muxin Yue

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(33)

Published: June 18, 2024

The diabetic wound healing is challenging due to the sabotaged delicate balance of immune regulation via an undetermined pathophysiological mechanism, so it crucial decipher multicellular signatures underlying and seek therapeutic strategies. Here, this work develops a strategy using novel trimethylamine N-oxide (TMAO)-derived zwitterionic hydrogel promote healing, explore multi-cellular ecosystem around hydrogel, mapping out overview different cells in microenvironment by single-cell RNA sequencing. diverse cellular heterogeneity revealed, highlighting critical role macrophage neutrophils managing healing. It found that polyzwitterionic can upregulate Ccl3+ macrophages downregulate S100a9+ facilitate their interactions compared with polyanionic polycationic hydrogels, validating effect on activation adaptive system. Moreover, inhibits formation neutrophil extracellular traps (NETs) promotes angiogenesis, thus improving These findings expand horizons sophisticated orchestration systems zwitterion-directed repair uncover new strategies immunoregulatory biomaterials.

Language: Английский

Citations

18
Multifunctional Sericin-Based Biomineralized Nanoplatforms with Immunomodulatory and Angio/Osteo-genic Activity for Accelerated Bone Regeneration in Periodontitis DOI

Piaoye Ming,

Bojiang Li,

Qiumei Li

et al.

Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122885 - 122885

Published: Oct. 10, 2024

Language: Английский

Citations

7
Engineered Macrophage Membrane‐Coated S100A9‐siRNA for Ameliorating Myocardial Ischemia‐Reperfusion Injury DOI Creative Commons
Lu H, Junzhuo Wang, Ziwei Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(41)

Published: Sept. 12, 2024

Abstract Despite the widespread adoption of emergency coronary reperfusion therapy, reperfusion‐induced myocardial injury remains a challenging issue in clinical practice. Following reperfusion, S100A8/A9 molecules are considered pivotal initiating and regulating tissue inflammatory damage. Effectively reducing level ischemic holds significant therapeutic value salvaging damaged myocardium. In this study, HA (hemagglutinin)‐ RAGE (receptor for advanced glycation end products)‐ comodified macrophage membrane‐coated siRNA nanoparticles (MMM/RNA NPs) with targeting S100A9 (S100A9‐siRNA) successfully prepared. This nanocarrier system is able to target effectively injured myocardium an environment while evading digestive damage by lysosomes. vivo, migration MMM/RNA NPs lesions confirmed ischemia‐reperfusion (MIRI) mouse model. Intravenous injection significantly reduced levels serum tissues, further decreasing infarction area improving cardiac function. Targeted reduction genetically modified may represent new intervention MIRI.

Language: Английский

Citations

6
Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells DOI Creative Commons
Bo Li, Wei Li,

Yueqi Liao

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

6
BMP2 peptide-modified polycaprolactone-collagen nanosheets for periodontal tissue regeneration DOI Creative Commons
Yong Zhang, Junxian Ren, Zongshan Shen

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 5, 2025

Periodontitis leads to the degradation of tooth-supporting tissues, ultimately causing tooth mobility and loss. Guided tissue regeneration (GTR) surgery employs barrier membranes facilitate regeneration. However, conventional lack bone-inducing properties, thereby limiting their efficacy. Our objective was develop a bifunctional GTR membrane that combines mechanical stability with capabilities. To achieve this, we engineered BMP2 peptide-modified polycaprolactone-collagen nanosheets (BPCNs) enhance periodontal by improving cell adhesion, osteogenesis, anti-inflammatory activity. BPCNs nanoscale thickness were fabricated using spin-coating technique, incorporating peptides, collagen, polycaprolactone (PCL), polyvinyl alcohol (PVA). Successful conjugation verified through UV spectrophotometry confocal laser scanning microscopy. The biocompatibility adhesion properties rigorously assessed CCK-8 assays, microscopic imaging, quantitative counting. In vitro osteogenic efficacy evaluated Alizarin Red S (ARS) staining reverse transcription polymerase chain reaction (qRT-PCR) analyze marker gene expression. A rat defect model established assess in vivo regenerative performance, outcomes analyzed micro-CT, hematoxylin-eosin (H&E) staining, Masson's trichrome confirming enhanced absence systemic toxicity. mechanistic pathways underlying BPCNs-mediated elucidated via RNA sequencing (RNA-seq), revealing activation signaling cascades suppression proinflammatory pathways. demonstrated excellent biocompatibility, promoted fibroblast bone marrow stem (BMSC) BMSC osteogenesis. Furthermore, significantly model. Mechanistically, RNA-seq analysis revealed upregulated genes involved downregulated This study introduced novel osteoinductive nanosheet, termed BPCNs, which provides groundbreaking material-based approach for repair defects. These findings position as highly promising candidate surgery, significant potential improve clinical medicine.

Language: Английский

Citations

0
An atlas of early human mandibular endochondral and osteogenic paracrine signaling regions of Meckel’s cartilage DOI Creative Commons
Zongshan Shen, Ran Zhang, Xinyue Chen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 17, 2025

The mandible, also known as the lower jaw, is only bone in skull that can move and essential for speaking chewing. Meckel’s cartilage (MC) a temporary structure supports formation of but how MC involved ossification mandible poorly understood. Through use single-cell RNA sequencing spatial transcriptomics analyses, spatiotemporal atlas human fetuses from 7 to 15 wk postconception was established, highlighting role mandible. Importantly, we revealed two populations contributed mandibular through different mechanisms. anterior differentiate into osteolineage cells, shown an vivo lineage tracing mouse model. intermediate facilitates intramembranous cell–cell communications, possibly signaling ligands like BMP5 , BMP7 SEMA3A PDGFC FGF7 . This study suggests plays crucial mediating distinct mechanisms, providing valuable insights understanding oral craniofacial diseases disorders future.

Language: Английский

Citations

0
Oral microbiome, periodontal disease and systemic bone-related diseases in the era of homeostatic medicine DOI Creative Commons

W L Hu,

Shuoling Chen,

Xianghui Zou

et al.

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Homeostasis is a state of self-regulation and dynamic equilibrium, maintaining the good physiological functions each system in living organisms. In oral cavity, interaction between host microbiome forms microbial homeostasis. Physiological bone remodeling renewal can occur under maintenance The imbalance homeostasis key mechanism leading to occurrence systemic bone-related diseases. Considering importance homeostasis, it still lacks complete understanding relationship microbiome, periodontal disease

Language: Английский

Citations

1
Engineering Peptide‐Oligonucleotide Nano‐Conjugates via Click Reaction as Self‐Delivery System for Gene Therapy of Inflammatory Arthritis DOI
Qing Wang, Wei Wang, Xiaole Peng

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(41)

Published: Aug. 20, 2024

Abstract Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, lysosomal phagocytosis, therapy remains a formidable challenge. The discovery cationic peptides has provided innovative insights the effective oligonucleotides, yet stable, efficient, convenient assembly oligonucleotides an elusive goal, referred to as “Holy Grail” challenge in field. Addressing this challenge, it pioneered development straightforward highly efficient engineering carrier‐free covalent peptide‐oligonucleotide nano‐conjugates (PONs) through mild click reaction. Notably, PONs can realize self‐assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase surprisingly well escape. Based on strategy, named CPP‐(DOPA) 6 ‐miRNA‐223 is synthesized, demonstrates rapid cellular uptake, swift escape macrophage, remarkable accumulation inflammatory regions excellent therapeutic effect arthritis model. Therefore, work may provide breakthrough clinical application all therapies expanding applications therapy.

Language: Английский

Citations

0
The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis DOI Creative Commons
Linrui Wu, Xiting Li, Jinyu Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 6, 2024

Periodontitis is a condition characterized by dysbiosis of microbiota and compromised host immunological responses, resulting in the degradation periodontal tissues. The aryl hydrocarbon receptor (AHR), ligand-activated transcription factor, plays crucial role pathogenesis periodontitis. AHR serves as pivotal mediator for adverse impacts exogenous pollutants on oral health. Research indicates elevated expression individuals with periodontitis compared to those without condition. However, subsequent identification endogenous ligands, researches have elucidated numerous significant advantageous roles associated activation bone, immune, epithelial cells. This review concentrates modulation pathway intricate functions that It discusses characteristics detailing established physiological maintaining alveolar bone equilibrium, regulating immunity, facilitating interactions between microbiome host, providing protection tissues, while also exploring its potential systemic disorders related

Language: Английский

Citations

0
Magnetic soft microrobots for erectile dysfunction therapy DOI Creative Commons
Shuting Wang, Zhenqing Wang, Zongshan Shen

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(49)

Published: Nov. 18, 2024

Erectile dysfunction (ED) is a major threat to male fertility and quality of life, mesenchymal stromal cells (MSCs) are promising therapeutic option. However, outcomes compromised by low MSC retention survival rates in corpus cavernosum tissue. Here, we developed an innovative magnetic soft microrobot comprising ultrasoft hydrogel microsphere embedded with nanoparticle chain for delivery. This design also features phenylboronic acid groups scavenging reactive oxygen species (ROS). With Young’s modulus less than 1 kPa, the adapts its shape within narrow blood vessels, ensuring uniform distribution MSCs cavernosum. Our findings showed that compared traditional injections, delivery (MSC-Rob) significantly enhanced survival. In both rat beagle ED models, MSC-Rob treatment accelerated repair tissue restored erectile function. Single-cell RNA sequencing (scRNA-seq) revealed facilitates nerve vessel regeneration increasing presence regenerative macrophages. Overall, our not only advances clinical application therapy but broadens scope microrobots other cell therapies.

Language: Английский

Citations

0