Critical roles of extracellular vesicles in periodontal disease and regeneration DOI Creative Commons

Jing Lin,

Hongyu Wang,

Ning Zhang

et al.

Stem Cells Translational Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Abstract Extracellular vesicles (EVs) are evolutionarily conserved communication mediators that play key roles in the development of periodontal disease as well regeneration processes. This concise review first outlines pathogenic mechanisms through which EVs derived from bacteria lead to progression periodontitis, with a focus on enrichment virulence factors, amplification immune responses, and induction bone destruction aspects influenced by bacterial EVs. aims elucidate positive effects mesenchymal stem cells (MSC-EVs) tissue regeneration. In particular, anti-inflammatory properties MSC-EVs their impact intricate interplay between MSCs various cells, including macrophages, dendritic T described. Moreover, recent advancements regarding repair-promoting functions detailed, highlighting underlying ability promote osteogenesis, cementogenesis, angiogenesis, homing thus contributing significantly Furthermore, this provides insights into therapeutic efficacy treating periodontitis within clinical context. By summarizing current knowledge, provide comprehensive understanding how can be harnessed for treatment diseases. Finally, discussion is presented challenges lie ahead potential practical implications translating EV-based therapies practices periodontitis.

Language: Английский

Biotin–Avidin System-Based Delivery Enhances the Therapeutic Performance of MSC-Derived Exosomes DOI
Dao‐Kun Deng, Xuan Li,

Jiu-Jiu Zhang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(9), P. 8530 - 8550

Published: April 28, 2023

Exosomes (EXs) shed by mesenchymal stem cells (MSCs) are potent therapeutic agents that promote wound healing and regeneration, but when used alone in vivo, their potency is diminished rapid clearance bioactivity loss. Inspired the biotin-avidin interaction, we developed a simple yet versatile method for immobilization of MSC-derived EXs (MSC-EXs) into hydrogels achieved sustained release regenerative purposes. First, biotin-modified gelatin methacryloyl (Bio-GelMA) was fabricated grafting NHS-PEG12-biotin onto amino groups GelMA. Biotin-modified MSC-EXs (Bio-EXs) were then synthesized using an situ self-assembling biotinylation strategy, which provided sufficient binding sites MSC-EX delivery with little effect on cargo composition. Thereafter, Bio-EXs immobilized Bio-GelMA via streptavidin to generate Bio-GelMA@Bio-EX hydrogels. An vitro analysis demonstrated could be taken up macrophages exerted immunomodulatory effects similar those MSC-EXs, 7 days. After subcutaneous transplantation, more constant retention observed 28 When placed artificial periodontal multitissue defect, functionalized exhibited optimized performance regrow complex tissues, including acellular cementum, ligaments (PDLs), alveolar bone. In this context, robust promoted macrophage polarization toward M2 phenotype. Our findings demonstrate delivered aid system exhibit macrophage-modulating repair-promoting functions suggest universal approach development MSC-EX-functionalized biomaterials advanced therapies.

Language: Английский

Citations

58
Unveiling clinical applications of bacterial extracellular vesicles as natural nanomaterials in disease diagnosis and therapeutics DOI Creative Commons
Chun Liu, Negar Yazdani, Corey S. Moran

et al.

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 180, P. 18 - 45

Published: April 17, 2024

Bacterial extracellular vesicles (BEVs) are naturally occurring bioactive membrane-bound nanoparticles released by both gram-negative and gram-positive bacterial species, exhibiting a multifaceted role in mediating host-microbe interactions across various physiological conditions. Increasing evidence supports BEVs as essential mediators of cell-to-cell communicaiton, influencing pathogenicity, disease mechanisms, modulating the host immune response. However, extent to which these BEV-mediated actions can be leveraged predict onset, guide treatment strategies, determine clinical outcomes remains uncertain, particularly terms their translation potentials. This review briefly describes BEV biogenesis internalisation recipient cells summarises methods for isolation characterization, understanding composition cargo. Further, it discusses potential biofluid-associated biomarkers diseases, spanning cancer non-cancerous Following this, we outline ongoing human trials using vaccine development. In addition diagnostics, this explores emerging research natural or engineered smart nanomaterials applications anti-cancer therapy bone regeneration. discussion extends key factors unlocking BEVs, such standardization characterisation, well other hurdles translating findings setting. We propose that addressing through collaborative efforts well-designed holds fully harnessing BEVs. As field advances, suggests BEV-based nanomedicine has revolutionize management, paving way innovative diagnosis, therapeutics, personalized medicine approaches. STATEMENT OF SIGNIFICANCE: Extracellular (EVs) from bacteria serve multifunctional biomaterials fields biomedicine, bioengineering, biomaterials. majority current studies focus on host-derived EVs, leaving gap comprehensive bacteria-derived EVs (BEVs). Although offer an attractive option drug delivery systems, unique nanostructure easy-to-modify functions make them method diagnosis Our work among pioneering investigating nanobiomaterials plays crucial development diseases therapeutic interventions.

Language: Английский

Citations

27
Microbial‐ and host immune cell‐derived extracellular vesicles in the pathogenesis and therapy of periodontitis: A narrative review DOI Creative Commons
Jenny Jing Wang, Chun Liu,

Jason Cutler

et al.

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

Published: May 17, 2024

Abstract Periodontitis is a chronic inflammatory disease caused by dysbiotic biofilms and destructive host immune responses. Extracellular vesicles (EVs) are circulating nanoparticles released microbes cells involved in cell‐to‐cell communication, found body biofluids, such as saliva gingival crevicular fluid (GCF). EVs mainly may hold promise for diagnostic therapeutic purposes. Periodontal research has examined the potential involvement of bacterial‐ host‐cell‐derived pathogenesis, diagnosis, therapy, but data remains scarce on cell‐ or microbial‐derived EVs. In this narrative review, we first provide an overview role microbial host‐derived pathogenesis. Recent studies reveal that Porphyromonas gingivalis Aggregatibacter actinomycetemcomitans ‐derived outer membrane (OMVs) can activate cytokine release cells, while M1 macrophage contribute to bone loss. Additionally, summarised current vitro pre‐clinical utilisation cell tools context periodontal treatment. Studies indicate from M2 macrophages dendritic promote regeneration animal models. While bacterial remain underexplored preliminary suggests P. OMVs vaccine candidates. Finally, acknowledge limitations present field translating derived periodontology. It concluded cell‐derived have periodontitis pathogenesis hence be useful studying pathophysiology, treatment monitoring biomarkers.

Language: Английский

Citations

8
Odontogenesis‐Empowered Extracellular Vesicles Safeguard Donor‐Recipient Stem Cell Interplay to Support Tooth Regeneration DOI
Xiaoyao Huang,

Bingdong Sui,

Anqi Liu

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Harnessing the developmental events of mesenchymal condensation to direct postnatal dental stem cell aggregation represents a cutting-edge and promising approach tooth regeneration. Tooth avulsion is among most prevalent serious injuries, odontogenic aggregates assembled by cells from human exfoliated deciduous teeth (SHED) have proven effective in revitalizing avulsed after replantation clinical trial. However, whether how SHED (SA) communicate with recipient components promote synergistic tissue regeneration support replanted remains elusive. Here, it shown that SA-mediated involves periodontal restoration recovery Gli1

Language: Английский

Citations

4
Therapeutic effect of mesenchymal stem cell-derived exosome therapy for periodontal regeneration: a systematic review and meta-analysis of preclinical trials DOI Creative Commons
Zhou Li-ping, Wenjia Cai, Yuhan Zhang

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 9, 2025

To assess the therapeutic effects of mesenchymal stem cell (MSC)-derived exosome therapy on periodontal regeneration and identify treatment factors associated with enhanced in recent preclinical studies. Searches were conducted PubMed, Cochrane Library, EMBASE, Web Science databases until October 10, 2024. A risk bias (ROB) assessment was performed using SYRCLE tool. Osteogenic-related parameters used as primary outcome measures. In total, 1360 articles identified, which 17 studies based MSC-derived therapy, they demonstrated a beneficial effect BV/TV (SMD = 13.99; 95% Cl 10.50, 17.48; p < 0.00001), CEJ-ABC -0.22; -0.31, -0.13; BMD 0.29; 0.14, 0.45; 0.0002), Tp.Sp -0.08; Cl= -0.15, -0.02; 0.02) compared control group. However, no significant differences observed Tp.Th 0.03; CI 0.00, 0.07; 0.09) between exosome-treated group Additionally, subgroup analysis indicated that preconditioned exosomes (p 0.03) significantly improved BV/TV. contrast, there enhancement respect to application method 0.29), frequency 0.10), duration 0.15), or source MSCs 0.31). show great promise for enhancing quality regeneration. more standardized robust trials are needed reduce heterogeneity across confirm by exosomes. CRD42024546236.

Language: Английский

Citations

0
Extracellular Vesicles in Periodontitis: Pathogenic Mechanisms and Therapeutic Potential DOI Creative Commons
Ling Zhang, Xiaotong Li,

Bin Zhang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1317 - 1331

Published: Jan. 1, 2025

Periodontitis is a prevalent yet frequently overlooked oral disease that linked to range of systemic conditions. Although basic treatment and periodontal surgery can alleviate the symptoms periodontitis certain extent, severe tissue defects or refractory cases not effective. Extracellular vesicles (EVs) are subcellular lipid bilayer particles come from variety sources in biological fluids vertebrates. They play key role intercellular communication by transporting multiple signaling molecules. Recent research has indicated EVs derived pathogens trigger periodontitis, exacerbate damage, potentially disseminate other parts body, leading Conversely, extracellular dental stem cells (DSCs) have demonstrated ability regulate local immune environment foster regeneration repair tissues, positioning them as promising candidate for cell-free therapeutic approaches periodontitis. This review aims summarize latest on involvement different pathogenesis especially systematically elucidate mechanism secreted periodontitis-related diseases first time. By uncovering these complex regulatory processes, new more effective be explored battle against its associated diseases.

Language: Английский

Citations

0
Exploring the therapeutic potential of small extracellular vesicles derived from induced pluripotent stem cell in periodontal regeneration DOI
Tingting Xu, Yi Peng,

Yanan Xu

et al.

Journal of Oral Biosciences, Journal Year: 2025, Volume and Issue: unknown, P. 100621 - 100621

Published: Jan. 1, 2025

Language: Английский

Citations

0
P. gingivalisOMVs Attenuate the Osteogenesis of PDLSCs by Activating PERK Signaling DOI Open Access
Yingying Huang,

Xiaoning He,

Jian‐You Liao

et al.

Oral Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

ABSTRACT Objective The Porphyromonas gingivalis outer membrane vesicles ( P. OMVs) carry toxins that contribute to the onset and progression of periodontitis. These OMVs have been implicated in host cell invasion damage. This study aimed determine role potential mechanisms on periodontal inflammation. Methods A model PDLSCs induced by was developed, changes their biological functions were examined. We established a rat periodontitis confirm whether OMV promotes inflammatory phenotype. Additionally, which impair osteogenic differentiation capacity investigated. Results inhibited proliferation, promoted apoptosis suppressed osteogenesis PDLSCs, while promoting phenotype vivo. Furthermore, mechanistic studies revealed pretreatment with 4‐phenylbutyric acid (4‐PBA) prevented OMVs‐induced activation PERK pathway restored PDLSCs. Conclusions demonstrate exacerbates inhibits regenerative function potentially through involving endoplasmic reticulum dysfunction.

Language: Английский

Citations

0
Bacterial growth stage determines the yields, protein composition, and periodontal pathogenicity of Porphyromonas gingivalis outer membrane vesicles DOI Creative Commons

Hongchen Mao,

Ting Gong,

Yuting Sun

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Oct. 11, 2023

P. gingivalis (W83), as the keystone pathogen in chronic periodontitis, has been found to be tightly bound systemic diseases. Outer membrane vesicles (OMVs) produced by (W83) are thought serve key functions bacterial virulence and pathogenicity. This study aims comprehend biological of OMVs isolated from different growth stages comparing their physicochemical properties pathogenicity.Protein composition was analyzed via isotope-labeled relative absolute quantification (iTRAQ). Macrophage polarization expression IL-6 IL-1β were detected. The proliferation, migration, osteogenic differentiation, IL-1b/NLRP3 periodontal ligament stem cells (PDLSCs) evaluated. gingivalis/P. OMVs-induced models also constructed Sprague Dawley rats.The protein demonstrated obvious differences ranging 25 KDa 75 KDa. In results flow cytometry, we that vitro experiments M1 subtype macrophages more abundant late-log stationary groups which boosted production inflammatory cytokines than pre-log OMVs. Compared OMVs, had pronounced inhibitory effects on early osteogenesis PDLSCs. NLRP3 inflammasome activated a larger extent group. Micro-computed tomography (Micro CT), hematoxylin-eosin staining (HE), tartrate acid phosphatase (TRAP) showed damage group worse group, but almost equal positive control (P. gingivalis).In general, both vivo have significant pathogenicity disease.

Language: Английский

Citations

9
Porphyromonas gingivalis Vaccine: Antigens and Mucosal Adjuvants DOI Creative Commons
Shuo Wang, Yan Tong,

Bingtao Zhang

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(6), P. 619 - 619

Published: June 4, 2024

Porphyromonas gingivalis (Pg), a Gram-negative anaerobic bacterium found in dental plaque biofilm within periodontal pockets, is the primary pathogenic microorganism responsible for chronic periodontitis. Infection by Pg significantly impacts development and progression of various diseases, underscoring importance eliminating this effective clinical treatment. While antibiotics are commonly used to combat Pg, rise antibiotic resistance poses challenge complete eradication. Thus, prevention infection paramount. Research suggests that surface antigens such as fimbriae, outer membrane proteins, gingipains, can potentially be utilized vaccine trigger protective immune responses. This article overviews these antigens, discusses advancements mucosal adjuvants (including immunostimulant vaccine-delivery adjuvants), their application development. Furthermore, review examines advantages disadvantages different pathways common routes immunization. By summarizing current landscape vaccines, addressing existing challenges, highlighting potential offers new insights advancement implementation vaccines.

Language: Английский

Citations

3