Abdel H Mahmoud, Aaron Sloutski, Shi Fu, Huiting Luo, Zoe Katevatis, Robert Wong, Yiwei Fang, Tatiana Zaliznyak, Fernando Aguilar Perez, Marcia Simon, Stephen G Walker, Thomas Manders, Miriam Rafailovich, Jerome J Cymerman
{"title":"一种创新的可注射和可回收的牙髓治疗药物输送系统。","authors":"Abdel H Mahmoud, Aaron Sloutski, Shi Fu, Huiting Luo, Zoe Katevatis, Robert Wong, Yiwei Fang, Tatiana Zaliznyak, Fernando Aguilar Perez, Marcia Simon, Stephen G Walker, Thomas Manders, Miriam Rafailovich, Jerome J Cymerman","doi":"10.1016/j.joen.2025.08.001","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Endodontic treatment failures remain a significant treatment challenge. Different bacterial combinations are implicated in posttreatment disease. Enterococcus faecalis is often detected in these biofilms. Calcium hydroxide has many limitations, including low flowability, difficult retrieval, high pH, and limited efficacy against E. faecalis. Here, we show that these difficulties can be overcome using calcium salicylate (CASA) encapsulated in a photocrosslinked thermoreversible F127-dimethacrylamide (DMA) hydrogel.</p><p><strong>Methods: </strong>CASA was prepared by mixing calcium hydroxide and salicylic acid in a 1:6 ratio, respectively and incorporated into F127-DMA at different concentrations. The mixture was photocrosslinked using lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate. Chemical properties were analyzed using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, while injectability and retrievability were assessed using plastic root canal training blocks, bovine teeth cone beam computed tomography scans, and oscillatory rheology. In Vitro antibacterial efficacy against E. faecalis biofilm was probed by injection of the compound, following inoculation on bovine extracted teeth. Cytotoxicity of the compound was measured using dental pulp stem cells.</p><p><strong>Results: </strong>Encapsulation of CASA in F127-DMA reduced the viscosity by three orders of magnitude compared to the paste form, facilitating injection and enabling retrieval. Following retrieval, F127-DMA/CASA showed significantly lower residual medicament (∼6%) compared to Vista-Cal (26%). X-ray diffraction, Raman, and Fourier transform infrared spectroscopy analyses confirmed the formation of CASA and successful integration of CASA into photocrosslinked F127-DMA. Treatment with the F127-DMA/20% CASA following 21-day inoculation with E. faecalis resulted in a 6-log reduction in CFU and complete elimination of biofilm. No significant change in the doubling time of treated dental pulp stem cell was observed.</p><p><strong>Conclusions: </strong>F127-DMA/CASA exhibits superior flowability, retrievability, near-neutral pH (∼6), biocompatibility, and anti-E. faecalis efficacy, which highlights its potential as a significant improvement over calcium hydroxide as an endodontic intracanal medicament.</p>","PeriodicalId":15703,"journal":{"name":"Journal of endodontics","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An Innovative Injectable and Retrievable Drug Delivery System for Endodontic Therapy.\",\"authors\":\"Abdel H Mahmoud, Aaron Sloutski, Shi Fu, Huiting Luo, Zoe Katevatis, Robert Wong, Yiwei Fang, Tatiana Zaliznyak, Fernando Aguilar Perez, Marcia Simon, Stephen G Walker, Thomas Manders, Miriam Rafailovich, Jerome J Cymerman\",\"doi\":\"10.1016/j.joen.2025.08.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Endodontic treatment failures remain a significant treatment challenge. Different bacterial combinations are implicated in posttreatment disease. Enterococcus faecalis is often detected in these biofilms. Calcium hydroxide has many limitations, including low flowability, difficult retrieval, high pH, and limited efficacy against E. faecalis. Here, we show that these difficulties can be overcome using calcium salicylate (CASA) encapsulated in a photocrosslinked thermoreversible F127-dimethacrylamide (DMA) hydrogel.</p><p><strong>Methods: </strong>CASA was prepared by mixing calcium hydroxide and salicylic acid in a 1:6 ratio, respectively and incorporated into F127-DMA at different concentrations. The mixture was photocrosslinked using lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate. Chemical properties were analyzed using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, while injectability and retrievability were assessed using plastic root canal training blocks, bovine teeth cone beam computed tomography scans, and oscillatory rheology. In Vitro antibacterial efficacy against E. faecalis biofilm was probed by injection of the compound, following inoculation on bovine extracted teeth. Cytotoxicity of the compound was measured using dental pulp stem cells.</p><p><strong>Results: </strong>Encapsulation of CASA in F127-DMA reduced the viscosity by three orders of magnitude compared to the paste form, facilitating injection and enabling retrieval. Following retrieval, F127-DMA/CASA showed significantly lower residual medicament (∼6%) compared to Vista-Cal (26%). X-ray diffraction, Raman, and Fourier transform infrared spectroscopy analyses confirmed the formation of CASA and successful integration of CASA into photocrosslinked F127-DMA. Treatment with the F127-DMA/20% CASA following 21-day inoculation with E. faecalis resulted in a 6-log reduction in CFU and complete elimination of biofilm. No significant change in the doubling time of treated dental pulp stem cell was observed.</p><p><strong>Conclusions: </strong>F127-DMA/CASA exhibits superior flowability, retrievability, near-neutral pH (∼6), biocompatibility, and anti-E. faecalis efficacy, which highlights its potential as a significant improvement over calcium hydroxide as an endodontic intracanal medicament.</p>\",\"PeriodicalId\":15703,\"journal\":{\"name\":\"Journal of endodontics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of endodontics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.joen.2025.08.001\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of endodontics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.joen.2025.08.001","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
An Innovative Injectable and Retrievable Drug Delivery System for Endodontic Therapy.
Introduction: Endodontic treatment failures remain a significant treatment challenge. Different bacterial combinations are implicated in posttreatment disease. Enterococcus faecalis is often detected in these biofilms. Calcium hydroxide has many limitations, including low flowability, difficult retrieval, high pH, and limited efficacy against E. faecalis. Here, we show that these difficulties can be overcome using calcium salicylate (CASA) encapsulated in a photocrosslinked thermoreversible F127-dimethacrylamide (DMA) hydrogel.
Methods: CASA was prepared by mixing calcium hydroxide and salicylic acid in a 1:6 ratio, respectively and incorporated into F127-DMA at different concentrations. The mixture was photocrosslinked using lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate. Chemical properties were analyzed using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, while injectability and retrievability were assessed using plastic root canal training blocks, bovine teeth cone beam computed tomography scans, and oscillatory rheology. In Vitro antibacterial efficacy against E. faecalis biofilm was probed by injection of the compound, following inoculation on bovine extracted teeth. Cytotoxicity of the compound was measured using dental pulp stem cells.
Results: Encapsulation of CASA in F127-DMA reduced the viscosity by three orders of magnitude compared to the paste form, facilitating injection and enabling retrieval. Following retrieval, F127-DMA/CASA showed significantly lower residual medicament (∼6%) compared to Vista-Cal (26%). X-ray diffraction, Raman, and Fourier transform infrared spectroscopy analyses confirmed the formation of CASA and successful integration of CASA into photocrosslinked F127-DMA. Treatment with the F127-DMA/20% CASA following 21-day inoculation with E. faecalis resulted in a 6-log reduction in CFU and complete elimination of biofilm. No significant change in the doubling time of treated dental pulp stem cell was observed.
Conclusions: F127-DMA/CASA exhibits superior flowability, retrievability, near-neutral pH (∼6), biocompatibility, and anti-E. faecalis efficacy, which highlights its potential as a significant improvement over calcium hydroxide as an endodontic intracanal medicament.
期刊介绍:
The Journal of Endodontics, the official journal of the American Association of Endodontists, publishes scientific articles, case reports and comparison studies evaluating materials and methods of pulp conservation and endodontic treatment. Endodontists and general dentists can learn about new concepts in root canal treatment and the latest advances in techniques and instrumentation in the one journal that helps them keep pace with rapid changes in this field.