Functional hydrogels for dental disease treatment

Abstract

Dental disease treatment has achieved significant progress, yet challenges remain due to limitations of conventional dental materials, including suboptimal biocompatibility and biodegradability. Functional hydrogels, as one kind of versatile biomaterial, have gained widespread attention in biomedical applications, offering notable advantages and promising potential for dental therapies. This paper summarizes the basic properties of functional hydrogels and recent advancements in treating various dental diseases. It emphasizes the working mechanisms and therapeutic effects. Lastly, the challenges and issues encountered by hydrogels in dental treatments are discussed, along with future development prospects. With ongoing advances in hydrogel design and fabrication, their performance is expected to improve further, expanding their role and potential in managing dental diseases, oral health, and related medical conditions.

Keywords

Functional hydrogels / dental disease treatment / tooth health

References

[1] Li H,Bao P.Recent advances in functional hydrogels for treating dental hard tissue and endodontic diseases.ACS Nano2024;18:16395-412

[2] Xu S,Dong T.Alleviate periodontitis and its comorbidity hypertension using a nanoparticle-embedded functional hydrogel system.Adv Healthc Mater2023;12:e2203337

[3] Gong J,Liu J.In situ oxygen-generating bio-heterojunctions for enhanced anti-bacterial treatment of anaerobe-induced periodontitis.Chem Eng J2024;498:155083

[4] Zhang F,Zhou Z.Blue-light-activated nano-TiO₂@PDA for highly effective and nondestructive tooth whitening.ACS Biomater Sci Eng2018;4:3072-7

[5] Gao J,Yue X.Photostable aggregation-induced emission photosensitizer nanoparticle/hyaluronic acid hydrogel for efficient photodynamic tooth bleaching.ACS Appl Nano Mater2022;5:5944-51

[6] Li Q,Xu Y.Fast cross-linked hydrogel as a green light-activated photocatalyst for localized biofilm disruption and brush-free tooth whitening.ACS Appl Mater Interfaces2022;14:28427-38

[7] Cheng K,Wang H.A bio-inspired versatile free-standing membrane for oral cavity microenvironmental monitoring and remineralization to prevent dental caries.Mater Horiz2023;10:512-23

[8] Wang D,Deng X,Zhang X.Controlling enamel remineralization by amyloid-like amelogenin mimics.Adv Mater2020;32:e2002080

[9] He J,Li M.Polyzwitterion manipulates remineralization and antibiofilm functions against dental demineralization.ACS Nano2022;16:3119-34

[10] Siddiqui Z,Kim KK.Angiogenic hydrogels for dental pulp revascularization.Acta Biomater2021;126:109-18 PMCID:PMC8096688

[11] Zheng L,Jiang L.Injectable decellularized dental pulp matrix-functionalized hydrogel microspheres for endodontic regeneration.Acta Biomater2023;156:37-48

[12] Li M,Yu K.A ROS-responsive hydrogel incorporated with dental follicle stem cell-derived small extracellular vesicles promotes dental pulp repair by ameliorating oxidative stress.Bioact Mater2024;36:524-40 PMCID:PMC11279300

[13] Liang Z,Lin H.Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.Acta Biomater2024;181:202-21

[14] Chung YL,Chien HH,Jeng JH.Interplay between diabetes mellitus and periodontal/pulpal-periapical diseases.J Dent Sci2024;19:1338-47 PMCID:PMC11259663

[15] Wang Y,Zhou Y,Huang C.Exploring relationships between circulating interleukins and pulp and periapical diseases: a bidirectional mendelian randomization study.J Endod2025;51:132-9

[16] Ribeiro JS,Ferreira JA.Injectable MMP-responsive nanotube-modified gelatin hydrogel for dental infection ablation.ACS Appl Mater Interfaces2020;12:16006-17 PMCID:PMC7370252

[17] Robberecht L,Meire M.Isthmus morphology influences debridement efficacy of activated irrigation: a laboratory study involving biofilm mimicking hydrogel removal and high-speed imaging.Int Endod J2023;56:118-27 PMCID:PMC10092478

[18] Wang Z,Huang Y,Chen J.Naturally sourced hydrogels: emerging fundamental materials for next-generation healthcare sensing.Chem Soc Rev2023;52:2992-3034

[19] Yin Y,Liu X,Han X.Biomaterials and therapeutic strategies designed for tooth extraction socket healing.Biomaterials2025;316:122975

[20] Reis A,Herrera DR,Loguercio AD.Clinical effects of prolonged application time of an in-office bleaching gel.Oper Dent2011;36:590-6

[21] Kielbassa AM,Gieren AK.Tooth sensitivity during and after vital tooth bleaching: a systematic review on an unsolved problem.Quintessence Int2015;46:881-97

[22] Huang Y,Shah S.Precision targeting of bacterial pathogen via bi-functional nanozyme activated by biofilm microenvironment.Biomaterials2021;268:120581 PMCID:PMC8182968

[23] Naha PC,Hwang G.Dextran-coated iron oxide nanoparticles as biomimetic catalysts for localized and pH-activated biofilm disruption.ACS Nano2019;13:4960-71 PMCID:PMC7059368

[24] Jia B,Li J.Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.Chem Soc Rev2024;53:3273-301

[25] Chen X,Wang D.Sulfated chitosan-modified CuS nanocluster: a versatile nanoformulation for simultaneous antibacterial and bone regenerative therapy in periodontitis.ACS Nano2024;18:14312-26

[26] Xiao M,Luo Y,Tao K.Engineering hydrogel-based conformal epidermal electrodes for human-machine interaction.Soft Sci2025;5:40

[27] You M,Yu H.Polyphenol-enhanced wet adhesive hydrogel with synergistic mechanical activation and ROS scavenging for accelerating diabetic wound healing.Chem Eng J2024;500:157103

[28] Deng D,Su K.Smart hydrogel dressing for machine learning-enabled visual monitoring and promote diabetic wound healing.Nano Today2025;60:102559

[29] Wen N,Jiang H.Bio-inspired self-healing hydrogel for fast hemostasis and accelerated wound healing of gastric ulcers.Adv Funct Mater2025;35:2411959

[30] Zhang D,Mao Y.Highly antifreezing thermogalvanic hydrogels for human heat harvesting in ultralow temperature environments.Nano Lett2023;23:11272-9

[31] Liu L,Bai P.Fatigue-resistant and super-tough thermocells.Nat Commun2025;16:1963 PMCID:PMC11861941

[32] Yang Q,Ding Q.An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis.Natl Sci Rev2024;11:nwae225 PMCID:PMC11275458

[33] Fang X,Ye C.Polyphenol-mediated redox-active hydrogel with H₂S gaseous-bioelectric coupling for periodontal bone healing in diabetes.Nat Commun2024;15:9071 PMCID:PMC11494015

[34] Dos Santos DM,Kim DS.Hierarchical chitin nanocrystal-based 3D printed dual-layer membranes hydrogels: a dual drug delivery nano-platform for periodontal tissue regeneration.ACS Nano2024;18:24182-203

[35] Ma Y,Chen Y.Biomimetic peridontium patches for functional periodontal regeneration.Adv Healthc Mater2023;12:e2202169

[36] Bai L,Wu J.An injectable adhesive hydrogel for photothermal ablation and antitumor immune activation against bacteria-associated oral squamous cell carcinoma.Acta Biomater2024;186:229-45

[37] Chen L,Zhang J.Prussian blue nanohybridized multicellular spheroids as composite engraftment for antioxidant bone regeneration and photoacoustic tomography.ACS Nano2024;18:24770-83

[38] He G,Lin H.An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration.Bioact Mater2024;37:106-18 PMCID:PMC11252469

[39] Ma S,Yao S.A deformable SIS/HA composite hydrogel coaxial scaffold promotes alveolar bone regeneration after tooth extraction.Bioact Mater2025;46:97-117 PMCID:PMC11697370

[40] Xing Q,Zhou X.Cohesion regulation of polyphenol cross-linked hydrogel adhesives: from intrinsic cross-link to designs of temporal responsiveness.Adv Funct Mater2025;35:2414294

[41] Li M,Zhu J.Clinically oriented oral environment-triggered underwater adhesives for root caries treatment through dentinal tubule occlusion and remineralization.ACS Appl Mater Interfaces2025;17:16576-89

[42] Liu S,Ma B,Liu H.Gingipain-responsive thermosensitive hydrogel loaded with SDF-1 facilitates in situ periodontal tissue regeneration.ACS Appl Mater Interfaces2021;13:36880-93

[43] Wu D,Wu Q.Preparation and characterization of Bomidin-loaded thermosensitive hydrogel for periodontal application.J Mater Res2022;37:3021-32

[44] Hao M,Wang W.HAp thermosensitive nanohydrogel cavities act as brood pouches to incubate and control-release NSCs for rapid spinal cord injury therapy.Adv Funct Mater2022;32:2203492

[45] Chen L,Zhou J.Supramolecular photothermal cascade nano-reactor enables photothermal effect, cascade reaction, and in situ hydrogelation for biofilm-associated tooth-extraction wound healing.Adv Mater2023;35:e2301664

[46] Sun J,Zhao B.Acceleration of oral wound healing under diabetes mellitus conditions using bioadhesive hydrogel.ACS Appl Mater Interfaces2023;15:416-31 PMCID:PMC9837818

[47] Zhang Z,Gao S,Guo J.Antibacterial, anti-inflammatory and wet-adhesive poly(ionic liquid)-based oral patch for the treatment of oral ulcers with bacterial infection.Acta Biomater2023;166:254-65

[48] Chen A,Lai J.Hydrogels for oral tissue engineering: challenges and opportunities.Molecules2023;28:3946 PMCID:PMC10179962

[49] Qi Y,Chi Y.Natural polyphenol self-assembled pH-responsive nanoparticles loaded into reversible hydrogel to inhibit oral bacterial activity.Mol Biomed2022;3:28 PMCID:PMC9478017

[50] Liu M,Xu X.Copper doped carbon dots for addressing bacterial biofilm formation, wound infection, and tooth staining.ACS Nano2022;16:9479-97

[51] Dai C,Xu Y.Wearable multifunctional hydrogel for oral microenvironment visualized sensing coupled with sonodynamic bacterial elimination and tooth whitening.Adv Healthc Mater2025;14:e2401269

[52] Deng S,Qiao Z.Hierarchically designed biodegradable polylactide particles with unprecedented piezocatalytic activity and biosafety for tooth whitening.Biomacromolecules2023;24:797-806

[53] Zhang H,Li Y.A bifunctional zwitterion-modified porphyrin for photodynamic nondestructive tooth whitening and biofilm eradication.Adv Funct Mater2021;31:2104799

[54] Wang Y,Meng Y.Pyro-catalysis for tooth whitening via oral temperature fluctuation.Nat Commun2022;13:4419 PMCID:PMC9338087

[55] Gao W,Li M.A drop-by-drop self-assembled all-natural hydrogel as a desensitizer for rapid and enduring management of dentin hypersensitivity.Adv Healthc Mater2024;13:e2303153

[56] Zhu J,Qiu R.Hagfish-inspired hydrogel for root caries: a multifunctional approach including immediate protection, antimicrobial phototherapy, and remineralization.Acta Biomater2024;188:117-37

[57] Muşat V,Zaharia A.A chitosan-agarose polysaccharide-based hydrogel for biomimetic remineralization of dental enamel.Biomolecules2021;11:1137 PMCID:PMC8392529

[58] Zhu J,Gao Y.Bionic wet-adhesive tooth band-aid with bidirectional anchoring to promote dentin remineralization.Chem Eng J2025;514:163314

[59] Soares DG,Swanson WB,Bottino MC.Platform technologies for regenerative endodontics from multifunctional biomaterials to tooth-on-a-chip strategies.Clin Oral Investig2021;25:4749-79 PMCID:PMC8546585

[60] Xie Z,Zhan P.Functional dental pulp regeneration: basic research and clinical translation.Int J Mol Sci2021;22:8991 PMCID:PMC8396610

[61] Eramo S,Pinna R.Dental pulp regeneration via cell homing.Int Endod J2018;51:405-19

[62] Wang S,Peng W.Fabrication of an exosome-loaded thermosensitive chitin-based hydrogel for dental pulp regeneration.J Mater Chem B2023;11:1580-90

[63] Park EH,Seo J,Kim HY.Efficacy of a novel remotely-generated ultrasonic root canal irrigation system for removing biofilm-mimicking hydrogel from a simulated isthmus model.Int Endod J2023;56:765-74

[64] Li T,Wu S.Super-rapid in situ formation of a silver ion-induced supramolecular hydrogel with efficient antibacterial activity for root canal disinfection.ACS Appl Mater Interfaces2023;15:29854-65

[65] Wang L,Bian F,Zhao Y.Self-bonded hydrogel inverse opal particles as sprayed flexible patch for wound healing.ACS Nano2022;16:2640-50

[66] Wang J,Liu Y.Bioinspired artificial liver system with hiPSC-derived hepatocytes for acute liver failure treatment.Adv Healthc Mater2021;10:e2101580

[67] Monteiro N,Athirasala A.Photopolymerization of cell-laden gelatin methacryloyl hydrogels using a dental curing light for regenerative dentistry.Dent Mater2018;34:389-99 PMCID:PMC5818302

[68] Xu F,Liu S.Injectable, ROS-scavenging, drug-loaded hydrogel dressings of natural origin for oral postoperative care.Mater Today Commun2023;35:105634

[69] Tan G,Yang L,Liu J.A multifunctional MOF-based nanohybrid as injectable implant platform for drug synergistic oral cancer therapy.Chem Eng J2020;390:124446