1. | Neshatian, Mehrnoosh; Holcroft, James; Kishen, Anil; Souza, Grace De; Ganss, Bernhard Promoting mineralization at biological interfaces Ex vivo with novel amelotin-based bio-nano complexes Journal Article In: Materials Today. Bio, vol. 14, pp. 100255, 2022, ISSN: 2590-0064. @article{Neshatian2022,
title = {Promoting mineralization at biological interfaces Ex vivo with novel amelotin-based bio-nano complexes},
author = {Mehrnoosh Neshatian and James Holcroft and Anil Kishen and Grace De Souza and Bernhard Ganss},
doi = {10.1016/j.mtbio.2022.100255},
issn = {2590-0064},
year = {2022},
date = {2022-01-01},
journal = {Materials Today. Bio},
volume = {14},
pages = {100255},
abstract = {Interfacial failure at the resin-dentin interface is a significant disadvantage of resin-based dental restoration. In this study, we created bio-inspired bio-nano complexes using the enamel protein amelotin (AMTN) or AMTN with an engineered collagen-binding site (AMTN-Col) to coat hydroxyapatite nanoparticles (HANP). The resulting nano-bio complexes, AMTN-HANP and AMTN-Col-HANP, were evaluated for their ability to promote collagen mineralization. Our study comprises three separate phases.In phase I, developing a method for functionalizing HANP with AMTN/AMTN-Col was explored. HANP were synthesized and characterized using TEM, SAED-TEM, XRD and ATR-FTIR. The nanoparticles were functionalized with AMTN or AMTN-Col. The successful coating of the nanoparticles with the proteins was confirmed using a TEM image of immunogold-labelled samples.In phase II of the study, the mineralization potential of the synthesized bio-nano complexes was studied using model systems consisting of simulated body fluid (SBF), polymerized collagen gels, and dentin disks prepared from human extracted molars. Mineral formation in SBF was recorded with a light scattering assay using a microplate reader on 8 replicates of each sample per study time point. Statistical analysis was performed using one-way ANOVA and the Tukey test. Significance was assigned at P 0.01. The extent of mineral formation on collagen gel and remineralization of demineralized dentin was studied with SEM. Accelerated mineral formation collagen mineralization of bio-nano complexes treated samples were observed in all model systems.In phase III of the study, the clinical utilization of AMTN/AMTN-Col coated HANP in bio-integration and enhancing the bond strength of a resin-based dental restoration and the dentin interface was investigated. The bio-nano complexes were applied as a pretreatment on dentin disks prepared from human extracted molars prior to the composite resin restoration. The micro-shear bond strength test was done on 8 samples per treatment group (a total of 32 samples). Statistical analysis on shear bond strength was performed using one-way ANOVA and the Tukey test. Significance was assigned at P 0.01. Shear bond strength values indicated that pretreatment of dentin with the bio-nano complexes before adhesive application significantly improved shear bond strength.
Conclusion: We have shown that AMTN based bio-nano complexes promote mineral formation on collagenous interfaces. Our findings can be the basis of new bio-inspired, bio-nano materials that may improve dental restoration longevity by enhancing the stability and integrity of the dentin-composite resin interface.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Interfacial failure at the resin-dentin interface is a significant disadvantage of resin-based dental restoration. In this study, we created bio-inspired bio-nano complexes using the enamel protein amelotin (AMTN) or AMTN with an engineered collagen-binding site (AMTN-Col) to coat hydroxyapatite nanoparticles (HANP). The resulting nano-bio complexes, AMTN-HANP and AMTN-Col-HANP, were evaluated for their ability to promote collagen mineralization. Our study comprises three separate phases.In phase I, developing a method for functionalizing HANP with AMTN/AMTN-Col was explored. HANP were synthesized and characterized using TEM, SAED-TEM, XRD and ATR-FTIR. The nanoparticles were functionalized with AMTN or AMTN-Col. The successful coating of the nanoparticles with the proteins was confirmed using a TEM image of immunogold-labelled samples.In phase II of the study, the mineralization potential of the synthesized bio-nano complexes was studied using model systems consisting of simulated body fluid (SBF), polymerized collagen gels, and dentin disks prepared from human extracted molars. Mineral formation in SBF was recorded with a light scattering assay using a microplate reader on 8 replicates of each sample per study time point. Statistical analysis was performed using one-way ANOVA and the Tukey test. Significance was assigned at P 0.01. The extent of mineral formation on collagen gel and remineralization of demineralized dentin was studied with SEM. Accelerated mineral formation collagen mineralization of bio-nano complexes treated samples were observed in all model systems.In phase III of the study, the clinical utilization of AMTN/AMTN-Col coated HANP in bio-integration and enhancing the bond strength of a resin-based dental restoration and the dentin interface was investigated. The bio-nano complexes were applied as a pretreatment on dentin disks prepared from human extracted molars prior to the composite resin restoration. The micro-shear bond strength test was done on 8 samples per treatment group (a total of 32 samples). Statistical analysis on shear bond strength was performed using one-way ANOVA and the Tukey test. Significance was assigned at P 0.01. Shear bond strength values indicated that pretreatment of dentin with the bio-nano complexes before adhesive application significantly improved shear bond strength.
Conclusion: We have shown that AMTN based bio-nano complexes promote mineral formation on collagenous interfaces. Our findings can be the basis of new bio-inspired, bio-nano materials that may improve dental restoration longevity by enhancing the stability and integrity of the dentin-composite resin interface. |
2. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights Into the May 2022 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 48, iss. 5, pp. 569-571, 2022, ISSN: 1878-3554. @article{Aminoshariae2022e,
title = {Insights Into the May 2022 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2022.03.007},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {5},
pages = {569-571},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
3. | Duque, Cristiane; Hussein, Hebatullah; Bortolatto, Janaina; Prakki, Anuradha; Kishen, Anil Effect of taxifolin and epigallocatechin-3-gallate on biomineralization potential of stem cells from dental apical papilla Journal Article In: Archives of Oral Biology, vol. 138, pp. 105413, 2022, ISSN: 1879-1506. @article{Duque2022,
title = {Effect of taxifolin and epigallocatechin-3-gallate on biomineralization potential of stem cells from dental apical papilla},
author = {Cristiane Duque and Hebatullah Hussein and Janaina Bortolatto and Anuradha Prakki and Anil Kishen},
doi = {10.1016/j.archoralbio.2022.105413},
issn = {1879-1506},
year = {2022},
date = {2022-01-01},
journal = {Archives of Oral Biology},
volume = {138},
pages = {105413},
abstract = {OBJECTIVE: Considering the variety of pharmacological activities and the potential to mediate biomineralization, the flavonoids taxifolin and epigallocatechin-3-gallate (EGCG) could be explored as biomolecules in scaffolds for regenerative endodontic procedures. The aim of this study was to evaluate the effect of taxifolin and EGCG on the cell viability, differentiation, and expression of biomineralization markers in stem cells from the apical papilla.
DESIGN: Stem cells from the apical papilla were exposed to single or continuous treatments with taxifolin at 200, 100 and 50 µM and EGCG at 50, 25 and 12.5 µM for 48 h, 8 and 14 days, in regular or mineralizing media. Cell viability, alkaline phosphatase activity and calcium deposition were analyzed using resazurin, p-nitrophenylphosphate and alizarin-based assays.
RESULTS: None of the flavonoid groups affected cell viability at 48 h, however at 8 and 14 days, Taxifolin 200 µM and EGCG 50 µM were cytotoxic. Cells did not express alkaline phosphatase activity when grown in regular medium, even in the presence of flavonoids. Alkaline phosphatase activity and biomineralization potential were higher in cells treated with Taxifolin 50 µM and EGCG 12.5 µM.
CONCLUSION: Taxifolin and EGCG exhibited a concentration, time, and therapeutic mode dependent bioactivity on stem cells from the apical papilla. Both flavonoids at the lower concentrations tested exhibited cytocompatibility and increased expression of mineralization markers in the presence of mineralizing agents.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Considering the variety of pharmacological activities and the potential to mediate biomineralization, the flavonoids taxifolin and epigallocatechin-3-gallate (EGCG) could be explored as biomolecules in scaffolds for regenerative endodontic procedures. The aim of this study was to evaluate the effect of taxifolin and EGCG on the cell viability, differentiation, and expression of biomineralization markers in stem cells from the apical papilla.
DESIGN: Stem cells from the apical papilla were exposed to single or continuous treatments with taxifolin at 200, 100 and 50 µM and EGCG at 50, 25 and 12.5 µM for 48 h, 8 and 14 days, in regular or mineralizing media. Cell viability, alkaline phosphatase activity and calcium deposition were analyzed using resazurin, p-nitrophenylphosphate and alizarin-based assays.
RESULTS: None of the flavonoid groups affected cell viability at 48 h, however at 8 and 14 days, Taxifolin 200 µM and EGCG 50 µM were cytotoxic. Cells did not express alkaline phosphatase activity when grown in regular medium, even in the presence of flavonoids. Alkaline phosphatase activity and biomineralization potential were higher in cells treated with Taxifolin 50 µM and EGCG 12.5 µM.
CONCLUSION: Taxifolin and EGCG exhibited a concentration, time, and therapeutic mode dependent bioactivity on stem cells from the apical papilla. Both flavonoids at the lower concentrations tested exhibited cytocompatibility and increased expression of mineralization markers in the presence of mineralizing agents. |
4. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the April 2022 Issue of the Journal of Endodontics Journal Article In: Journal of Endodontics, vol. 48, iss. 4, pp. 427-429, 2022, ISSN: 1878-3554. @article{Aminoshariae2022d,
title = {Insights into the April 2022 Issue of the Journal of Endodontics},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2022.02.014},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {4},
pages = {427-429},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
5. | Faggion, Clovis M; Nagendrababu, Venkateshbabu; Abbott, Paul V; Boutsioukis, Christos; Duncan, Henry F; Kishen, Anil; Murray, Peter E; Dummer, Paul M H Need for criteria to appraise the methodological quality of laboratory-based studies included in systematic reviews within the speciality of Endodontology Journal Article In: International Endodontic Journal, vol. 55, iss. 4, pp. 278-281, 2022, ISSN: 1365-2591. @article{Faggion2022,
title = {Need for criteria to appraise the methodological quality of laboratory-based studies included in systematic reviews within the speciality of Endodontology},
author = {Clovis M Faggion and Venkateshbabu Nagendrababu and Paul V Abbott and Christos Boutsioukis and Henry F Duncan and Anil Kishen and Peter E Murray and Paul M H Dummer},
doi = {10.1111/iej.13700},
issn = {1365-2591},
year = {2022},
date = {2022-01-01},
journal = {International Endodontic Journal},
volume = {55},
issue = {4},
pages = {278-281},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
6. | Li, Fang-Chi; Shahin-Shamsabadi, Alireza; Selvaganapathy, P Ravi; Kishen, Anil Engineering a Novel Stem Cells from Apical Papilla-Macrophages Organoid for Regenerative Endodontics Journal Article In: Journal of Endodontics, pp. S0099–2399(22)00153–4, 2022, ISSN: 1878-3554. @article{Li2022,
title = {Engineering a Novel Stem Cells from Apical Papilla-Macrophages Organoid for Regenerative Endodontics},
author = {Fang-Chi Li and Alireza Shahin-Shamsabadi and P Ravi Selvaganapathy and Anil Kishen},
doi = {10.1016/j.joen.2022.02.011},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
pages = {S0099\textendash2399(22)00153\textendash4},
abstract = {INTRODUCTION: A 3-dimensional (3D) tissue construct with a heterogeneous cell population is critical to understand the interactions between immune cells and stem cells from the apical papilla (SCAPs) in the periapical region for developing treatment strategies in regenerative endodontics. This study aimed to develop and characterize a 3D tissue construct with a binary cell system for studying the interactions between SCAPs and macrophages in the presence of lipopolysaccharide (proinflammatory) and interleukin 4 (anti-inflammatory) environments.
METHODS: SCAPs and macrophages were seeded in the 3D-printed dumbbell-shaped molds to generate tissue constructs with a binary cell population. Two experimental (lipopolysaccharide and interleukin 4) and control (non-stimulation) conditions were applied to the tissue constructs to determine the characteristics of the tissue construct, the volume of viable cells, and their morphology using confocal laser scanning microscopy from a 0- to 7-day period. Experiments were conducted in triplicate, and data were analyzed with trend analysis and 2-way analysis of variance at a significance of P .05.
RESULTS: The tissue constructs revealed distinct SCAP-macrophage interaction in pro/anti-inflammatory environments. SCAPs displayed characteristic self-organization as a cap-shaped structure in the tissue construct. The growth of cells and cell-to-cell and cell-to-matrix interactions resulted in 70% and 30% decreased dimension of the tissue graft on the SCAP side and macrophage side, respectively, at day 7 (P .0001). The tissue environments influenced SCAP-macrophage interactions, resulting in an altered viable cell volume (P .05), morphology, and structural organization.
CONCLUSIONS: This study developed and characterized an apical papilla organoid in a 3D collagen-based tissue construct for studying SCAP-macrophage crosstalk in tissue regeneration as well as repair.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: A 3-dimensional (3D) tissue construct with a heterogeneous cell population is critical to understand the interactions between immune cells and stem cells from the apical papilla (SCAPs) in the periapical region for developing treatment strategies in regenerative endodontics. This study aimed to develop and characterize a 3D tissue construct with a binary cell system for studying the interactions between SCAPs and macrophages in the presence of lipopolysaccharide (proinflammatory) and interleukin 4 (anti-inflammatory) environments.
METHODS: SCAPs and macrophages were seeded in the 3D-printed dumbbell-shaped molds to generate tissue constructs with a binary cell population. Two experimental (lipopolysaccharide and interleukin 4) and control (non-stimulation) conditions were applied to the tissue constructs to determine the characteristics of the tissue construct, the volume of viable cells, and their morphology using confocal laser scanning microscopy from a 0- to 7-day period. Experiments were conducted in triplicate, and data were analyzed with trend analysis and 2-way analysis of variance at a significance of P .05.
RESULTS: The tissue constructs revealed distinct SCAP-macrophage interaction in pro/anti-inflammatory environments. SCAPs displayed characteristic self-organization as a cap-shaped structure in the tissue construct. The growth of cells and cell-to-cell and cell-to-matrix interactions resulted in 70% and 30% decreased dimension of the tissue graft on the SCAP side and macrophage side, respectively, at day 7 (P .0001). The tissue environments influenced SCAP-macrophage interactions, resulting in an altered viable cell volume (P .05), morphology, and structural organization.
CONCLUSIONS: This study developed and characterized an apical papilla organoid in a 3D collagen-based tissue construct for studying SCAP-macrophage crosstalk in tissue regeneration as well as repair. |
7. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the March 2022 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 48, iss. 3, pp. 295-297, 2022, ISSN: 1878-3554. @article{Aminoshariae2022c,
title = {Insights into the March 2022 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2022.01.018},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {3},
pages = {295-297},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
8. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the February 2022 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 48, iss. 2, pp. 141-143, 2022, ISSN: 1878-3554. @article{Aminoshariae2022b,
title = {Insights into the February 2022 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2022.01.005},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {2},
pages = {141-143},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
9. | Hussein, Hebatullah; Kishen, Anil Proteomic profiling reveals engineered chitosan nanoparticles mediated cellular crosstalk and immunomodulation for therapeutic application in apical periodontitis Journal Article In: Bioactive Materials, vol. 11, pp. 77-89, 2022, ISSN: 2452-199X. @article{Hussein2022b,
title = {Proteomic profiling reveals engineered chitosan nanoparticles mediated cellular crosstalk and immunomodulation for therapeutic application in apical periodontitis},
author = {Hebatullah Hussein and Anil Kishen},
doi = {10.1016/j.bioactmat.2021.09.032},
issn = {2452-199X},
year = {2022},
date = {2022-01-01},
journal = {Bioactive Materials},
volume = {11},
pages = {77-89},
abstract = {Macrophages (MQ) are major constituents of chronically inflamed periapical tissues in apical periodontitis. This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles (CSnp) antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts (PdLF). Cells viability, spreading, PdLF migration, and intracellular CSnp uptake were characterized. Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm, CSnp-treated biofilm, and CSnp. Secreted inflammatory mediators were analyzed. Following bioinformatics analyses, candidate proteins were validated via targeted proteomics. CSnp maintained cells viability, increased MQ spreading, and PdLF migration (p 0.05). Transmission electron micrographs demonstrated CSnp internalization via macropinocytosis, clathrin-mediated endocytosis, and phagocytosis. Proteomic analysis revealed that CSnp-treated biofilm upregulated proteins (1.5-folds, p 0.05) showed functional enrichment in the pathway of metal sequestration by antimicrobial proteins, while downregulated proteins showed enrichment in ferroptosis. CSnp upregulated proteins exhibiting antioxidant and immunoregulatory properties. Upregulation of SERPINB1 by CSnp (1.5-folds, p 0.05) was validated. CSnp-treated biofilm reduced pro-inflammatory IL-1β and nitric oxide but enhanced anti-inflammatory IL-10 and TGF-β1 (p 0.05). Internalized engineered bioactive CSnp reprogrammed MQ proteomic and cytokine profiles to modulate biofilm-mediated inflammation, and prompted PdLF migration, emphasizing its potential to regulate healing process in the treatment of apical periodontitis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Macrophages (MQ) are major constituents of chronically inflamed periapical tissues in apical periodontitis. This study aimed to investigate the immunomodulatory effect of engineered bioactive chitosan-based nanoparticles (CSnp) antibiofilm medication on MQ cocultured with periodontal ligament fibroblasts (PdLF). Cells viability, spreading, PdLF migration, and intracellular CSnp uptake were characterized. Tandem Mass Tag-based proteomics was applied to analyze MQ global protein expression profiles after interaction with Enterococcus faecalis biofilm, CSnp-treated biofilm, and CSnp. Secreted inflammatory mediators were analyzed. Following bioinformatics analyses, candidate proteins were validated via targeted proteomics. CSnp maintained cells viability, increased MQ spreading, and PdLF migration (p 0.05). Transmission electron micrographs demonstrated CSnp internalization via macropinocytosis, clathrin-mediated endocytosis, and phagocytosis. Proteomic analysis revealed that CSnp-treated biofilm upregulated proteins (1.5-folds, p 0.05) showed functional enrichment in the pathway of metal sequestration by antimicrobial proteins, while downregulated proteins showed enrichment in ferroptosis. CSnp upregulated proteins exhibiting antioxidant and immunoregulatory properties. Upregulation of SERPINB1 by CSnp (1.5-folds, p 0.05) was validated. CSnp-treated biofilm reduced pro-inflammatory IL-1β and nitric oxide but enhanced anti-inflammatory IL-10 and TGF-β1 (p 0.05). Internalized engineered bioactive CSnp reprogrammed MQ proteomic and cytokine profiles to modulate biofilm-mediated inflammation, and prompted PdLF migration, emphasizing its potential to regulate healing process in the treatment of apical periodontitis. |
10. | Hussein, Hebatullah; Kishen, Anil Local Immunomodulatory Effects of Intracanal Medications in Apical Periodontitis Journal Article In: Journal of Endodontics, vol. 48, iss. 4, pp. 430-456, 2022, ISSN: 1878-3554. @article{Hussein2022,
title = {Local Immunomodulatory Effects of Intracanal Medications in Apical Periodontitis},
author = {Hebatullah Hussein and Anil Kishen},
doi = {10.1016/j.joen.2022.01.003},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {4},
pages = {430-456},
abstract = {The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP), and periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly because of the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered posttreatment healing to exacerbation of chronic periradicular immune response, which compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment; however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. The interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of nonconventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect without any host tissue damages. In this review, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobial intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The immune system is an extremely complex biological network that plays a crucial role in the hemostasis of periapical tissue, pathogenesis of apical periodontitis (AP), and periapical tissue healing. The successful elimination of microbial infections remains a significant challenge, mostly because of the ever-growing development of antimicrobial-resistant pathogens. The bacterial endurance in the root canal system contributes to features ranging from altered posttreatment healing to exacerbation of chronic periradicular immune response, which compromise the outcome of endodontic treatment. A highly effective strategy for combating infectious diseases and the associated inflammation-mediated tissue damage is to modulate the host immune response in conjunction with antimicrobial therapy. There are several medications currently used in endodontic treatment; however, they suffer various levels of microbial resistance and do not deliver all the required characteristics to simultaneously address both intracanal bacteria and periapical inflammation. The interaction of antimicrobial agents with the immune system can impact its function, leading to immune-suppressive or immune-stimulatory effects. The group of nonconventional antimicrobial medications, such as antimicrobial peptides, propolis, and nanomaterials, are agents that provide strong antimicrobial effectiveness and concomitant immunomodulatory and/or reparative effect without any host tissue damages. In this review, we provide an overview of local immune modulation in AP and a comprehensive review of the immunomodulatory effect of antimicrobial intracanal medications applied in endodontics with specific emphasis on the antimicrobial nanomaterial-based approaches that provide immunomodulatory potential for successful clinical deployment in endodontics. |
11. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the January 2022 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 48, iss. 1, pp. 1-3, 2022, ISSN: 1878-3554. @article{Aminoshariae2022,
title = {Insights into the January 2022 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.11.017},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {1},
pages = {1-3},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
12. | Bakhtiar, Hengameh; Ashoori, Azin; Rajabi, Sarah; Pezeshki-Modaress, Mohamad; Ayati, Alireza; Mousavi, Mohammad Reza; Ellini, Mohammad Reza; Kamali, Amir; Azarpazhooh, Amir; Kishen, Anil Human amniotic membrane extracellular matrix scaffold for dental pulp regeneration in vitro and in vivo Journal Article In: International Endodontic Journal, vol. 55, iss. 4, pp. 374-390, 2022, ISSN: 1365-2591. @article{Bakhtiar2022,
title = {Human amniotic membrane extracellular matrix scaffold for dental pulp regeneration in vitro and in vivo},
author = {Hengameh Bakhtiar and Azin Ashoori and Sarah Rajabi and Mohamad Pezeshki-Modaress and Alireza Ayati and Mohammad Reza Mousavi and Mohammad Reza Ellini and Amir Kamali and Amir Azarpazhooh and Anil Kishen},
doi = {10.1111/iej.13675},
issn = {1365-2591},
year = {2022},
date = {2022-01-01},
journal = {International Endodontic Journal},
volume = {55},
issue = {4},
pages = {374-390},
abstract = {AIM: In order to obtain a 3-dimentional scaffold with predictable clinical results for pulp regeneration, this study aims to fabricate and characterize a porous decellularized human amniotic membrane (HAM) extracellular matrix (ECM) scaffold, and evaluate its potential to promote pulp regeneration in vitro and in vivo.
METHODOLOGY: The HAM was decellularized, and its histology and DNA content were analysed to confirm decellularization. The scaffolds were synthesized with 15, 22.5 and 30 mg/ml concentrations. The porosity, pore size, phosphate-buffered saline (PBS) absorption and degradation rate of the scaffolds were assessed. In vitro experiments were performed on human dental pulp stem cells (hDPSCs) to assess their viability, proliferation, adhesion and migration on the scaffolds. The optimal group was selected for in vivo immunogenicity assessment and was also used as the cell-free or cell-loaded scaffold in root segment models to evaluate pulp regeneration. All nonparametric data were analysed with the Kruskal-Wallis test followed by Dunn's post hoc test, whilst quantitative data were analysed with one-way anova.
RESULTS: Decellularization of HAM was confirmed (p .05). The porosity of all scaffolds was more than 95%, and the pore size decreased with an increase in ECM concentration (p .01). PBS absorption was not significantly different amongst the groups, whilst 30 mg/ml ECM scaffold had the highest degradation rate (p .01). The hDPSCs adhered to the scaffold, whilst their proliferation rate increased over time in all groups (p .001). Cell migration was higher in 30 mg/ml ECM scaffold (p .05). In vivo investigation with 30 mg/ml ECM scaffold revealed mild to moderate inflammatory response. In root segments, both cell-free and cell-loaded 30 mg/ml scaffolds were replaced with newly formed, pulp-like tissue with no significant difference between groups. Immunohistochemical assessments revealed high revascularization and collagen content with no significant difference amongst the groups.
CONCLUSION: The 30 mg/ml HAM ECM scaffold had optimal physical properties and better supported hDPSC migration. The HAM ECM scaffold did not interfere with formation of pulp-like tissue and revascularization within the root canal when employed as both cell-free and cell-loaded scaffold. These results highlight the potential of HAM ECM membrane for further investigations in regenerative endodontics.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AIM: In order to obtain a 3-dimentional scaffold with predictable clinical results for pulp regeneration, this study aims to fabricate and characterize a porous decellularized human amniotic membrane (HAM) extracellular matrix (ECM) scaffold, and evaluate its potential to promote pulp regeneration in vitro and in vivo.
METHODOLOGY: The HAM was decellularized, and its histology and DNA content were analysed to confirm decellularization. The scaffolds were synthesized with 15, 22.5 and 30 mg/ml concentrations. The porosity, pore size, phosphate-buffered saline (PBS) absorption and degradation rate of the scaffolds were assessed. In vitro experiments were performed on human dental pulp stem cells (hDPSCs) to assess their viability, proliferation, adhesion and migration on the scaffolds. The optimal group was selected for in vivo immunogenicity assessment and was also used as the cell-free or cell-loaded scaffold in root segment models to evaluate pulp regeneration. All nonparametric data were analysed with the Kruskal-Wallis test followed by Dunn's post hoc test, whilst quantitative data were analysed with one-way anova.
RESULTS: Decellularization of HAM was confirmed (p .05). The porosity of all scaffolds was more than 95%, and the pore size decreased with an increase in ECM concentration (p .01). PBS absorption was not significantly different amongst the groups, whilst 30 mg/ml ECM scaffold had the highest degradation rate (p .01). The hDPSCs adhered to the scaffold, whilst their proliferation rate increased over time in all groups (p .001). Cell migration was higher in 30 mg/ml ECM scaffold (p .05). In vivo investigation with 30 mg/ml ECM scaffold revealed mild to moderate inflammatory response. In root segments, both cell-free and cell-loaded 30 mg/ml scaffolds were replaced with newly formed, pulp-like tissue with no significant difference between groups. Immunohistochemical assessments revealed high revascularization and collagen content with no significant difference amongst the groups.
CONCLUSION: The 30 mg/ml HAM ECM scaffold had optimal physical properties and better supported hDPSC migration. The HAM ECM scaffold did not interfere with formation of pulp-like tissue and revascularization within the root canal when employed as both cell-free and cell-loaded scaffold. These results highlight the potential of HAM ECM membrane for further investigations in regenerative endodontics. |
13. | Singh, Kamna; Ali, Aiman; Shrestha, Annie; Magalhaes, Marco; Kishen, Anil Assessing Macrophage Polarization in Nanoparticle-Guided Wound Repair Using a Lipopolysaccharide Contaminated Intraosseous Model Journal Article In: Journal of Endodontics, vol. 48, iss. 1, pp. 109-116, 2022, ISSN: 1878-3554. @article{Singh2022,
title = {Assessing Macrophage Polarization in Nanoparticle-Guided Wound Repair Using a Lipopolysaccharide Contaminated Intraosseous Model},
author = {Kamna Singh and Aiman Ali and Annie Shrestha and Marco Magalhaes and Anil Kishen},
doi = {10.1016/j.joen.2021.09.011},
issn = {1878-3554},
year = {2022},
date = {2022-01-01},
journal = {Journal of Endodontics},
volume = {48},
issue = {1},
pages = {109-116},
abstract = {INTRODUCTION: Macrophages regulate the processes of inflammation and tissue regeneration/repair through their plasticity and phenotypes of different activation states. Previous studies have shown that disinfection of lipopolysaccharide (LPS)-contaminated dentin with photoactivated rose bengal-functionalized chitosan nanoparticles (CSRBnps) in vivo supported neotissue formation without signs of inflammation and root resorption. The aim of this study was to understand the mechanism underlying CSRBnp-guided attenuation of inflammation in LPS-contaminated dentin using macrophage polarization as an indicator of inflammation and repair. METHODS: To quantify the polarized macrophage populations, M1/M2-specific surface markers CD68, CD80, and CD206 and transcriptional factors signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 were determined using immunohistochemistry among previously obtained root specimens implanted into mandibles of guinea pigs for 4 weeks. In group 1, the canals were not inoculated; in group 2, the canals were inoculated with Pseudomonas aeruginosa LPS; in group 3, the canals were inoculated and disinfected with sodium hypochlorite; in group 4, the canals were inoculated and disinfected with sodium hypochlorite and calcium hydroxide; and in group 5, the canals were inoculated and disinfected with sodium hypochlorite, and CSRBnps (300 μg/mL) with photoactivation (λ = 540 nm, 40 J/cm2) were analyzed.
RESULTS: An increased expression of M2-specific markers was observed in the group treated with CSRBnps compared with the groups treated with either conventional or no root canal disinfection. A statistically significant population of macrophages expressing both M1- and M2-specific markers was observed in all the tested groups.
CONCLUSIONS: Disinfection of LPS-contaminated dentin with CSRBnps demonstrated M2-type polarization of macrophages, which corresponded to repair and neotissue formation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Macrophages regulate the processes of inflammation and tissue regeneration/repair through their plasticity and phenotypes of different activation states. Previous studies have shown that disinfection of lipopolysaccharide (LPS)-contaminated dentin with photoactivated rose bengal-functionalized chitosan nanoparticles (CSRBnps) in vivo supported neotissue formation without signs of inflammation and root resorption. The aim of this study was to understand the mechanism underlying CSRBnp-guided attenuation of inflammation in LPS-contaminated dentin using macrophage polarization as an indicator of inflammation and repair. METHODS: To quantify the polarized macrophage populations, M1/M2-specific surface markers CD68, CD80, and CD206 and transcriptional factors signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 were determined using immunohistochemistry among previously obtained root specimens implanted into mandibles of guinea pigs for 4 weeks. In group 1, the canals were not inoculated; in group 2, the canals were inoculated with Pseudomonas aeruginosa LPS; in group 3, the canals were inoculated and disinfected with sodium hypochlorite; in group 4, the canals were inoculated and disinfected with sodium hypochlorite and calcium hydroxide; and in group 5, the canals were inoculated and disinfected with sodium hypochlorite, and CSRBnps (300 μg/mL) with photoactivation (λ = 540 nm, 40 J/cm2) were analyzed.
RESULTS: An increased expression of M2-specific markers was observed in the group treated with CSRBnps compared with the groups treated with either conventional or no root canal disinfection. A statistically significant population of macrophages expressing both M1- and M2-specific markers was observed in all the tested groups.
CONCLUSIONS: Disinfection of LPS-contaminated dentin with CSRBnps demonstrated M2-type polarization of macrophages, which corresponded to repair and neotissue formation. |
14. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; He, Jianing; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Roda, Robert S; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the December 2021 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 47, iss. 12, pp. 1817-1819, 2021, ISSN: 1878-3554. @article{Aminoshariae2021j,
title = {Insights into the December 2021 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Jianing He and Anil Kishen and Ariadne M Letra and Linda Levin and Robert S Roda and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.10.007},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {12},
pages = {1817-1819},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
15. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Roda, Robert S; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the November 2021 Issue of the Journal of Endodontics Journal Article In: Journal of Endodontics, vol. 47, iss. 11, pp. 1669-1671, 2021, ISSN: 1878-3554. @article{Aminoshariae2021i,
title = {Insights into the November 2021 Issue of the Journal of Endodontics},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Anil Kishen and Ariadne M Letra and Linda Levin and Robert S Roda and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.09.013},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {11},
pages = {1669-1671},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
16. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Roda, Robert S; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the October 2021 Issue of the Journal of Endodontics Journal Article In: Journal of Endodontics, vol. 47, iss. 10, pp. 1547-1549, 2021, ISSN: 1878-3554. @article{Aminoshariae2021h,
title = {Insights into the October 2021 Issue of the Journal of Endodontics},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Anil Kishen and Ariadne M Letra and Linda Levin and Robert S Roda and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.08.011},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {10},
pages = {1547-1549},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
17. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Roda, Robert S; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the September 2021 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 47, iss. 9, pp. 1337-1339, 2021, ISSN: 1878-3554. @article{Aminoshariae2021g,
title = {Insights into the September 2021 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Anil Kishen and Ariadne M Letra and Linda Levin and Robert S Roda and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.07.019},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {9},
pages = {1337-1339},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
18. | Marashdeh, Muna Q; Stewart, Cameron A; Kishen, Anil; Levesque, Celine; Finer, Yoav Assessment of Root Canal Sealers Loaded with Drug-Silica Coassembled Particles Using an In Vitro Tooth Model Journal Article In: Journal of Endodontics, vol. 47, iss. 11, pp. 1775-1782, 2021, ISSN: 1878-3554. @article{Marashdeh2021b,
title = {Assessment of Root Canal Sealers Loaded with Drug-Silica Coassembled Particles Using an In Vitro Tooth Model},
author = {Muna Q Marashdeh and Cameron A Stewart and Anil Kishen and Celine Levesque and Yoav Finer},
doi = {10.1016/j.joen.2021.08.005},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {11},
pages = {1775-1782},
abstract = {INTRODUCTION: The purpose of this study was to assess the antimicrobial activity of root canal sealers modified with novel highly loaded antimicrobial drug-silica coassembled particles (DSPs) on Enterococcus faecalis-infected root canal dentin.
METHODS: DSPs were synthesized through coassembly of silica and octenidine dihydrochloride (OCT) surfactant drug (35% w/w OCT). DSPs (1% wt of the total mass of the sealer) were mixed homogenously with either epoxy resin sealer (AH Plus [AH]; Dentsply Sirona, Tulsa, OK) or calcium silicate-based sealer (EndoSequence BC Sealer [BC]; Brasseler, Savannah, GA). To assess the antimicrobial activity of DSP-loaded sealers, the apical third of single-rooted teeth was obtained and infected with E. faecalis for 3 weeks followed by the application of experimental (DSP-loaded) sealers or corresponding controls for up to 28 days. Microbiological analysis and laser scanning confocal and scanning electron microscopy were used to determine the colony-forming unit (CFU)/mL, the percentage of live bacteria, and the intratubular bacterial and sealer penetrations. Factorial analysis of variance and Tukey post hoc tests were used to assess the antimicrobial effect of DSPs on different sealers.
RESULTS: All experimental groups showed significant reductions in CFUs at all-time points compared with positive controls (P .05). The addition of DSPs to BC significantly reduced the CFUs (2.11 ± 0.13, 2.22 ± 0.19, and 2.25 ± 0.17 at 1, 7, and 28 days, respectively) compared with the unmodified sealer (3.21 ± 0.11, 4.3 ± 0.15, and 4.2 ± 0.2 at 0, 7, and 28 days). DSPs enhanced the antimicrobial performance of AH only at 1 day (4.21 ± 0.17 vs 5.19 ± 0.12, P .05). AH and AH + DSPs showed higher bacterial viability compared with BC and BC + DSPs at all incubation periods (P .05).
CONCLUSIONS: Loading endodontic sealers with DSPs had a material-dependent effect on the antimicrobial properties and could reduce the incidence of secondary infections.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: The purpose of this study was to assess the antimicrobial activity of root canal sealers modified with novel highly loaded antimicrobial drug-silica coassembled particles (DSPs) on Enterococcus faecalis-infected root canal dentin.
METHODS: DSPs were synthesized through coassembly of silica and octenidine dihydrochloride (OCT) surfactant drug (35% w/w OCT). DSPs (1% wt of the total mass of the sealer) were mixed homogenously with either epoxy resin sealer (AH Plus [AH]; Dentsply Sirona, Tulsa, OK) or calcium silicate-based sealer (EndoSequence BC Sealer [BC]; Brasseler, Savannah, GA). To assess the antimicrobial activity of DSP-loaded sealers, the apical third of single-rooted teeth was obtained and infected with E. faecalis for 3 weeks followed by the application of experimental (DSP-loaded) sealers or corresponding controls for up to 28 days. Microbiological analysis and laser scanning confocal and scanning electron microscopy were used to determine the colony-forming unit (CFU)/mL, the percentage of live bacteria, and the intratubular bacterial and sealer penetrations. Factorial analysis of variance and Tukey post hoc tests were used to assess the antimicrobial effect of DSPs on different sealers.
RESULTS: All experimental groups showed significant reductions in CFUs at all-time points compared with positive controls (P .05). The addition of DSPs to BC significantly reduced the CFUs (2.11 ± 0.13, 2.22 ± 0.19, and 2.25 ± 0.17 at 1, 7, and 28 days, respectively) compared with the unmodified sealer (3.21 ± 0.11, 4.3 ± 0.15, and 4.2 ± 0.2 at 0, 7, and 28 days). DSPs enhanced the antimicrobial performance of AH only at 1 day (4.21 ± 0.17 vs 5.19 ± 0.12, P .05). AH and AH + DSPs showed higher bacterial viability compared with BC and BC + DSPs at all incubation periods (P .05).
CONCLUSIONS: Loading endodontic sealers with DSPs had a material-dependent effect on the antimicrobial properties and could reduce the incidence of secondary infections. |
19. | Aminoshariae, Anita; Azarpazhooh, Amir; Diogenes, Anibal R; Fouad, Ashraf F; Glickman, Gerald N; Kishen, Anil; Letra, Ariadne M; Levin, Linda; Roda, Robert S; Setzer, Frank C; Tay, Franklin R; Hargreaves, Kenneth M Insights into the August 2021 Issue of the JOE Journal Article In: Journal of Endodontics, vol. 47, iss. 8, pp. 1195-1197, 2021, ISSN: 1878-3554. @article{Aminoshariae2021f,
title = {Insights into the August 2021 Issue of the JOE},
author = {Anita Aminoshariae and Amir Azarpazhooh and Anibal R Diogenes and Ashraf F Fouad and Gerald N Glickman and Anil Kishen and Ariadne M Letra and Linda Levin and Robert S Roda and Frank C Setzer and Franklin R Tay and Kenneth M Hargreaves},
doi = {10.1016/j.joen.2021.06.016},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {8},
pages = {1195-1197},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
20. | Hussein, Hebatullah; Kishen, Anil Engineered Chitosan-based Nanoparticles Modulate Macrophage-Periodontal Ligament Fibroblast Interactions in Biofilm-mediated Inflammation Journal Article In: Journal of Endodontics, vol. 47, iss. 9, pp. 1435-1444, 2021, ISSN: 1878-3554. @article{Hussein2021,
title = {Engineered Chitosan-based Nanoparticles Modulate Macrophage-Periodontal Ligament Fibroblast Interactions in Biofilm-mediated Inflammation},
author = {Hebatullah Hussein and Anil Kishen},
doi = {10.1016/j.joen.2021.06.017},
issn = {1878-3554},
year = {2021},
date = {2021-01-01},
journal = {Journal of Endodontics},
volume = {47},
issue = {9},
pages = {1435-1444},
abstract = {INTRODUCTION: Crosstalk between immune cells and tissue-resident cells regulates the pathophysiology and posttreatment healing of apical periodontitis. This investigation aimed to understand the influence of residual root canal biofilm on macrophage (MQ)-periodontal ligament fibroblast (PdLF) interaction and evaluate the effect of engineered chitosan-based nanoparticles (CSnp) on MQ-PdLF interactions in residual biofilm-mediated inflammation. METHODS: Six-week-old Enterococcus faecalis biofilms in root canal models were disinfected conventionally using sodium hypochlorite alone or followed by calcium hydroxide medication or CSnp dispersed in carboxymethylated chitosan (CMCS). The effect of the treated biofilms (n = 25/group) on the inflammatory response of THP-1-differentiated MQ monoculture versus coculture with PdLF was evaluated for cell viability, MQ morphometric characterization, inflammatory mediators (nitric oxide, tumor necrosis factor alpha, interleukin [IL]-1 beta, IL-1RA, IL-6, transforming growth factor beta 1 [TGF-β1], and IL-10), and the expression of transcription factors (pSTAT1/pSTAT6)/cluster of differentiation markers (CD80/206) after 24, 48, and 72 hours of interaction. PdLF transwell migration was evaluated after 8 and 24 hours. Unstimulated cells served as the negative control, whereas untreated biofilm was the positive control.
RESULTS: Biofilm increased nitric oxide and IL-1β but suppressed IL-10, IL-1RA, and PdLF migration with significant cytotoxic effects. CSnp/CMCS reduced nitric oxide and IL-1β (P .01) while maintaining ≥90% cell survival up to 72 hours with evident M2-like MQ phenotypic changes in coculture. CSnp/CMCS also increased the IL-1RA/IL-1β ratio and enhanced TGF-β1 production over time (P .05, 72 hours). In coculture, CSnp/CMCS showed the highest IL-10 level at 72 hours (P .01), reduced the pSTAT1/pSTAT6 ratio, and enhanced PdLF migration (P .01, 24 hours).
CONCLUSIONS: CSnp/CMCS medication facilitated MQ switch toward M2 (regulatory/anti-inflammatory) phenotype and PdLF migration via paracrine signaling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Crosstalk between immune cells and tissue-resident cells regulates the pathophysiology and posttreatment healing of apical periodontitis. This investigation aimed to understand the influence of residual root canal biofilm on macrophage (MQ)-periodontal ligament fibroblast (PdLF) interaction and evaluate the effect of engineered chitosan-based nanoparticles (CSnp) on MQ-PdLF interactions in residual biofilm-mediated inflammation. METHODS: Six-week-old Enterococcus faecalis biofilms in root canal models were disinfected conventionally using sodium hypochlorite alone or followed by calcium hydroxide medication or CSnp dispersed in carboxymethylated chitosan (CMCS). The effect of the treated biofilms (n = 25/group) on the inflammatory response of THP-1-differentiated MQ monoculture versus coculture with PdLF was evaluated for cell viability, MQ morphometric characterization, inflammatory mediators (nitric oxide, tumor necrosis factor alpha, interleukin [IL]-1 beta, IL-1RA, IL-6, transforming growth factor beta 1 [TGF-β1], and IL-10), and the expression of transcription factors (pSTAT1/pSTAT6)/cluster of differentiation markers (CD80/206) after 24, 48, and 72 hours of interaction. PdLF transwell migration was evaluated after 8 and 24 hours. Unstimulated cells served as the negative control, whereas untreated biofilm was the positive control.
RESULTS: Biofilm increased nitric oxide and IL-1β but suppressed IL-10, IL-1RA, and PdLF migration with significant cytotoxic effects. CSnp/CMCS reduced nitric oxide and IL-1β (P .01) while maintaining ≥90% cell survival up to 72 hours with evident M2-like MQ phenotypic changes in coculture. CSnp/CMCS also increased the IL-1RA/IL-1β ratio and enhanced TGF-β1 production over time (P .05, 72 hours). In coculture, CSnp/CMCS showed the highest IL-10 level at 72 hours (P .01), reduced the pSTAT1/pSTAT6 ratio, and enhanced PdLF migration (P .01, 24 hours).
CONCLUSIONS: CSnp/CMCS medication facilitated MQ switch toward M2 (regulatory/anti-inflammatory) phenotype and PdLF migration via paracrine signaling. |