Dynamic Covalent Colloidal Gel via RISA for Treating Synergistic Progression of Periodontitis and Dental Demineralization

preprint OA: closed
Full text JSON View at publisher

Abstract

Abstract Severe periodontitis and tooth demineralization are two prevalent yet pathophysiologically distinct oral diseases that frequently coexist, forming a vicious cycle closely associated with pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). However, current therapeutic approaches typically target either inflammation or hard tissue loss in isolation, lacking adaptability and synergy for complex oral comorbidities. Here, we identified key therapeutic targets for the combined treatment of severe periodontitis with concomitant demineralization based on multidimensional clinical sample analysis. Subsequently, we present a multifunctional colloidal gel platform (PFE CGs) with a dynamic covalent colloidal network using the reaction-induced self-assembly (RISA) technique. Catechol groups in PFE CG ensure strong adhesion to tooth surfaces, creating a stable interface for remineralization. The positively charged three-dimensional (3D) network of PFE CGs enables efficient adsorption of PAMPs and DAMPs, suppressing toll-like receptor (TLR) 4/9-mediated inflammatory signaling and modulating macrophage’s inflammation. Under the acidic and oxidative stress conditions of periodontitis, dynamic covalent bonds are reversibly cleaved to release anti-inflammatory and antioxidant agents, and neutralize the acidic microenvironment that promotes demineralization. This RISA-based colloidal gel platform offers a comprehensive strategy for the synergistic treatment of inflammation and demineralization, and holds promise for managing complex oral comorbidities and guiding the design of next-generation bioactive materials.
Full text 15,126 characters · extracted from preprint-html · click to expand
Dynamic Covalent Colloidal Gel via RISA for Treating Synergistic Progression of Periodontitis and Dental Demineralization | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Dynamic Covalent Colloidal Gel via RISA for Treating Synergistic Progression of Periodontitis and Dental Demineralization Yong Liu, Haoyue Wu, Jing Shen, Fan Yang, Yuhan Zhao, Yi Wu, Keqing Jin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7437803/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Severe periodontitis and tooth demineralization are two prevalent yet pathophysiologically distinct oral diseases that frequently coexist, forming a vicious cycle closely associated with pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). However, current therapeutic approaches typically target either inflammation or hard tissue loss in isolation, lacking adaptability and synergy for complex oral comorbidities. Here, we identified key therapeutic targets for the combined treatment of severe periodontitis with concomitant demineralization based on multidimensional clinical sample analysis. Subsequently, we present a multifunctional colloidal gel platform (PFE CGs) with a dynamic covalent colloidal network using the reaction-induced self-assembly (RISA) technique. Catechol groups in PFE CG ensure strong adhesion to tooth surfaces, creating a stable interface for remineralization. The positively charged three-dimensional (3D) network of PFE CGs enables efficient adsorption of PAMPs and DAMPs, suppressing toll-like receptor (TLR) 4/9-mediated inflammatory signaling and modulating macrophage’s inflammation. Under the acidic and oxidative stress conditions of periodontitis, dynamic covalent bonds are reversibly cleaved to release anti-inflammatory and antioxidant agents, and neutralize the acidic microenvironment that promotes demineralization. This RISA-based colloidal gel platform offers a comprehensive strategy for the synergistic treatment of inflammation and demineralization, and holds promise for managing complex oral comorbidities and guiding the design of next-generation bioactive materials. Health sciences/Diseases/Oral diseases/Periodontitis Physical sciences/Materials science/Biomaterials/Drug delivery Full Text Additional Declarations There is NO Competing Interest. Supplementary Files DatasetHYW20250822.xlsx Supplementary data set SIHYW20250822.pdf Supplementary materials SupplementaryMovie1.mp4 Supplementary Movie 1 SupplementaryMovie2.mp4 Supplementary Movie 2 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7437803","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":510452245,"identity":"8b08554f-387a-46f4-8a31-f638fcb91662","order_by":0,"name":"Yong Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYFAC5oYDDBVAmoeB4QCQR4wWRqCWM6RqYWBsg2hhIEqLwQHGxsO88+7Im/Mcfgh0oXViA/vZA4S0NBzm3fbMcGdvmwHQhemJDTx5CcRoOcy44TyI3XY4sUGCx4AILXMO2284z/7hAOM/orU0HE7ccLYHzCasRfIwY8PBOccOJ284c6bgQMKxdOM2nhz8WviONx/+8KbmsO2GM+mbP3yosZbtZz+DX4vCYWReAhCz4VUPBPINhFSMglEwCkbBKAAAb4BPL2GjDYEAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-1738-7857","institution":"Nankai University","correspondingAuthor":true,"prefix":"","firstName":"Yong","middleName":"","lastName":"Liu","suffix":""},{"id":510452246,"identity":"cf6531f8-0239-471e-8c35-c26c76ebfe05","order_by":1,"name":"Haoyue Wu","email":"","orcid":"https://orcid.org/0009-0002-3712-0877","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Haoyue","middleName":"","lastName":"Wu","suffix":""},{"id":510452247,"identity":"b8590e86-1160-42ad-b6a5-0efb8388fc65","order_by":2,"name":"Jing Shen","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Shen","suffix":""},{"id":510452248,"identity":"6238d470-fcca-45c1-ac06-6f833e04ad7d","order_by":3,"name":"Fan Yang","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Fan","middleName":"","lastName":"Yang","suffix":""},{"id":510452249,"identity":"a2441fc0-9a2d-4e2a-87a9-86658e934564","order_by":4,"name":"Yuhan Zhao","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"Zhao","suffix":""},{"id":510452250,"identity":"8a4a4e71-7d8c-4758-9bd4-51816c1b22fd","order_by":5,"name":"Yi Wu","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Wu","suffix":""},{"id":510452251,"identity":"7c762f11-8100-46d2-b752-0eb297744a66","order_by":6,"name":"Keqing Jin","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Keqing","middleName":"","lastName":"Jin","suffix":""},{"id":510452252,"identity":"d455cd24-e4a9-4883-806f-269b5dab332e","order_by":7,"name":"Yuanfeng Li","email":"","orcid":"https://orcid.org/0009-0002-9139-3139","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuanfeng","middleName":"","lastName":"Li","suffix":""},{"id":510452253,"identity":"1db02369-e54a-4916-be0f-d853f99e7edf","order_by":8,"name":"Linqi Shi","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Linqi","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2025-08-23 00:55:10","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7437803/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7437803/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96915848,"identity":"eefd39bf-143a-4096-abd6-24002f38cde0","added_by":"auto","created_at":"2025-11-27 14:07:41","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3763881,"visible":true,"origin":"","legend":"Article File","description":"","filename":"manscriptHYW.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7437803/v1_covered_2aa5b9e2-82cb-4a02-8ed4-2e5587f73ef0.pdf"},{"id":90782692,"identity":"b9d79b34-d665-476a-b247-09df74191d69","added_by":"auto","created_at":"2025-09-08 06:06:05","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":926407,"visible":true,"origin":"","legend":"Supplementary data set","description":"","filename":"DatasetHYW20250822.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7437803/v1/7578bbf5b8322916d28b5a18.xlsx"},{"id":90782694,"identity":"dbb854ed-3f30-45f2-af15-343ce92b5ee9","added_by":"auto","created_at":"2025-09-08 06:06:05","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":3928585,"visible":true,"origin":"","legend":"Supplementary materials","description":"","filename":"SIHYW20250822.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7437803/v1/8476ce824bd4feaf1e0b1e8f.pdf"},{"id":90782695,"identity":"30f2ac03-6481-4ec9-a891-f3ebc91897ad","added_by":"auto","created_at":"2025-09-08 06:06:05","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":14671589,"visible":true,"origin":"","legend":"Supplementary Movie 1","description":"","filename":"SupplementaryMovie1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7437803/v1/dfc3c46e532456eb2a225706.mp4"},{"id":90782696,"identity":"5e72486d-dbc5-4e29-bfc8-303408483c54","added_by":"auto","created_at":"2025-09-08 06:06:05","extension":"mp4","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":14819039,"visible":true,"origin":"","legend":"Supplementary Movie 2","description":"","filename":"SupplementaryMovie2.mp4","url":"https://assets-eu.researchsquare.com/files/rs-7437803/v1/b3c7b3ef716ec5e5955d485a.mp4"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Dynamic Covalent Colloidal Gel via RISA for Treating Synergistic Progression of Periodontitis and Dental Demineralization","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7437803/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7437803/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Severe periodontitis and tooth demineralization are two prevalent yet pathophysiologically distinct oral diseases that frequently coexist, forming a vicious cycle closely associated with pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). However, current therapeutic approaches typically target either inflammation or hard tissue loss in isolation, lacking adaptability and synergy for complex oral comorbidities. Here, we identified key therapeutic targets for the combined treatment of severe periodontitis with concomitant demineralization based on multidimensional clinical sample analysis. Subsequently, we present a multifunctional colloidal gel platform (PFE CGs) with a dynamic covalent colloidal network using the reaction-induced self-assembly (RISA) technique. Catechol groups in PFE CG ensure strong adhesion to tooth surfaces, creating a stable interface for remineralization. The positively charged three-dimensional (3D) network of PFE CGs enables efficient adsorption of PAMPs and DAMPs, suppressing toll-like receptor (TLR) 4/9-mediated inflammatory signaling and modulating macrophage’s inflammation. Under the acidic and oxidative stress conditions of periodontitis, dynamic covalent bonds are reversibly cleaved to release anti-inflammatory and antioxidant agents, and neutralize the acidic microenvironment that promotes demineralization. This RISA-based colloidal gel platform offers a comprehensive strategy for the synergistic treatment of inflammation and demineralization, and holds promise for managing complex oral comorbidities and guiding the design of next-generation bioactive materials.","manuscriptTitle":"Dynamic Covalent Colloidal Gel via RISA for Treating Synergistic Progression of Periodontitis and Dental Demineralization","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-08 06:06:00","doi":"10.21203/rs.3.rs-7437803/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"120e76f9-bf22-42b1-b054-6a5fc276f4e9","owner":[],"postedDate":"September 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":54221591,"name":"Health sciences/Diseases/Oral diseases/Periodontitis"},{"id":54221592,"name":"Physical sciences/Materials science/Biomaterials/Drug delivery"}],"tags":[],"updatedAt":"2026-03-12T02:45:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-08 06:06:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7437803","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7437803","identity":"rs-7437803","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00