{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:27:46Z","timestamp":1786512466676,"version":"build-2736575974"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Regenerative endodontic therapy aims to restore the pulp-dentin complex through biological approaches; however, current cell-free techniques often fail to achieve true dental pulp regeneration and may result in fibrous tissue formation or canal calcification. This study investigated dynamic hydrogels as advanced scaffolds for dental pulp stem cell (DPSC)-mediated regeneration, leveraging their viscoelastic properties to regulate cellular behavior and immune responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Dynamic hydrogels were synthesized using host-guest chemistry (Gel-Mal\/HA-Ada-CD-SH) to mimic aspects of the native extracellular matrix and were compared with non-dynamic Gel-Mal hydrogels. DPSCs and macrophages were encapsulated within the hydrogels to evaluate cellular viability, morphology, inflammatory marker expression, and gene expression profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Dynamic hydrogels exhibited a distinct porous microarchitecture and significantly increased NF-\u03baB and VEGF expression while reducing IL-1RA expression compared with non-dynamic hydrogels. Gene expression analysis demonstrated significantly increased TGF\u03b21, SMAD3, and MAPK expression, together with reduced CD80 expression, in macrophages cultured within dynamic hydrogels. Although iNOS expression was lower in the dynamic hydrogel group, the difference was not statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that dynamic hydrogels do not simply suppress inflammatory signaling but may modulate inflammatory and tissue remodeling pathways while promoting angiogenesis-associated responses. Limitations of the study include the short-term in vitro design and evaluation of a limited panel of inflammatory and fibrosis-associated markers. Within these limitations, dynamic hydrogels demonstrated favorable cellular and immunomodulatory responses and may provide a biologically active microenvironment that supports cellular activities relevant to regenerative endodontic applications. Further in vivo studies are required to validate their translational potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fdmed.2026.1847615","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:38:40Z","timestamp":1786509520000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Application of dynamic hydrogels for dental pulp regeneration: a comparative study on cellular behavior and inflammatory modulation"],"prefix":"10.3389","volume":"7","author":[{"given":"Yara","family":"AlMaimouni","sequence":"first","affiliation":[{"name":"Department of Restorative Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University","place":["Dammam, Saudi Arabia"]},{"name":"School of Dentistry, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shorouq","family":"Houtari","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of California, Los Angeles","place":["Los Angeles, CA, United States"]},{"name":"Department of Restorative Sciences, College of Dentistry, Kuwait University","place":["Safat, Kuwait"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Moshaverinia","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","volume-title":"Glossary of Endodontic Terms","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.joen.2011.01.011","article-title":"Regenerative endodontic treatment (revascularization) for necrotic immature permanent molars: a review and report of two cases with a new biomaterial","volume":"37","author":"Nosrat","year":"2011","journal-title":"J Endod"},{"key":"B3","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.adaj.2016.01.009","article-title":"Regenerative endodontics: a way forward","volume":"147","author":"Diogenes","year":"2016","journal-title":"J Am Dent Assoc"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13287-017-0506-5","article-title":"Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: a pilot clinical study","volume":"8","author":"Nakashima","year":"2017","journal-title":"Stem Cell Res Ther"},{"key":"B5","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1177\/0022034517693606","article-title":"Decellularized human dental pulp as a scaffold for regenerative endodontics","volume":"96","author":"Song","year":"2017","journal-title":"J Dent Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1111\/iej.12591","article-title":"In vitro assessment of a collagen\/alginate composite scaffold for regenerative endodontics","volume":"50","author":"Devillard","year":"2017","journal-title":"Int Endod J"},{"key":"B7","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.joen.2009.03.049","article-title":"Formation of dentinal bridge on surface of regenerated dental pulp in dentin defects by controlled release of fibroblast growth factor-2 from gelatin hydrogels","volume":"35","author":"Ishimatsu","year":"2009","journal-title":"J Endod"},{"key":"B8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.dental.2012.08.002","article-title":"A hydrogel scaffold that maintains viability and supports differentiation of dental pulp stem cells","volume":"29","author":"Cavalcanti","year":"2013","journal-title":"Dent Mater"},{"key":"B9","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.joen.2017.11.003","article-title":"EDTA Treatment for sodium hypochlorite\u2013treated dentin recovers disturbed attachment and induces differentiation of mouse dental papilla cells","volume":"44","author":"Hashimoto","year":"2018","journal-title":"J Endod"},{"key":"B10","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1002\/term.2397","article-title":"Bioactive injectable aggregates with nanofibrous microspheres and human dental pulp stem cells: a translational strategy in dental endodontics","volume":"12","author":"Garz\u00f3n","year":"2018","journal-title":"J Tissue Eng Regen Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3390\/jcs9080424","article-title":"An injectable, dual-curing hydrogel for controlled bioactive release in regenerative endodontics","volume":"9","author":"Omidi","year":"2025","journal-title":"J Compos Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"61638","DOI":"10.1021\/acsami.1c18701","article-title":"Injectable and self-healing hydrogels with double-dynamic bond tunable mechanical, gel\u2013sol transition and drug delivery properties for promoting periodontium regeneration in periodontitis","volume":"13","author":"Guo","year":"2021","journal-title":"ACS Appl Mater Interfaces"},{"key":"B13","doi-asserted-by":"publisher","first-page":"eaay6853","DOI":"10.1126\/scitranslmed.aay6853","article-title":"An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats","volume":"12","author":"Hasani-Sadrabadi","year":"2020","journal-title":"Sci Transl Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"989","DOI":"10.3390\/ijms18050989","article-title":"Drug-loadable calcium alginate hydrogel system for use in oral bone tissue repair","volume":"18","author":"Chen","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","first-page":"111158","DOI":"10.1016\/j.msec.2020.111158","article-title":"Injectable hydrogel-loaded nano-hydroxyapatite that improves bone regeneration and alveolar ridge promotion","volume":"116","author":"Pan","year":"2020","journal-title":"Mater Sci Eng C"},{"key":"B16","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41536-023-00286-3","article-title":"Biomineralization-inspired mineralized hydrogel promotes the repair and regeneration of dentin\/bone hard tissue","volume":"8","author":"Wen","year":"2023","journal-title":"NPJ Regen Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1177\/154405910508401105","article-title":"NF-\u03baB activation in human dental pulp stem cells by TNF and LPS","volume":"84","author":"Chang","year":"2005","journal-title":"J Dent Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.bioactmat.2024.12.026","article-title":"Injectable thermosensitive antibiotic-laden chitosan hydrogel for regenerative endodontics","volume":"46","author":"Reis-Prado","year":"2025","journal-title":"Bioact Mater"},{"key":"B19","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/s41586-020-2612-2","article-title":"Effects of extracellular matrix viscoelasticity on cellular behaviour","volume":"584","author":"Chaudhuri","year":"2020","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41536-025-00414-1","article-title":"An NF-kB\/TNF-alpha signalling feedback loop acts to coordinate tissue regeneration and macrophage behaviour in zebrafish","volume":"10","author":"Arkoudi","year":"2025","journal-title":"npj Regen Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1126\/science.aad9272","article-title":"Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells","volume":"352","author":"Sadtler","year":"2016","journal-title":"Science"}],"container-title":["Frontiers in Dental Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2026.1847615\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T04:38:50Z","timestamp":1786509530000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fdmed.2026.1847615\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":21,"alternative-id":["10.3389\/fdmed.2026.1847615"],"URL":"https:\/\/doi.org\/10.3389\/fdmed.2026.1847615","relation":{},"ISSN":["2673-4915"],"issn-type":[{"value":"2673-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"article-number":"1847615"}}