切换至 "中华医学电子期刊资源库"

中华口腔医学研究杂志(电子版) ›› 2026, Vol. 20 ›› Issue (05) : 372 -382. doi: 10.3877/cma.j.issn.1674-1366.2026.05.004

口腔感染微生态专栏·综述

益生菌水凝胶在龋病防治中的研究进展
钟婷婷1, 陈梓锋1, 杨金鑫1, 张少冰2, 吴文震1,3,†()   
  1. 1广东医科大学附属东莞第一医院口腔医学中心,东莞 523710
    2广东医科大学东莞市医学活性分子开发与转化重点实验室,东莞 523808
    3思南县人民医院,铜仁 565100
  • 收稿日期:2026-04-26 出版日期:2026-10-01
  • 通信作者: 吴文震

Research progress of probiotic hydrogels in the prevention and treatment of dental caries

Tingting Zhong1, Zifeng Chen1, Jinxin Yang1, Shaobing Zhang2, Wenzhen Wu1,3,†()   

  1. 1Center for Oral Medicine, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan 523710, China
    2Key Laboratory of Development and Translation of Medical Active Molecules, Guangdong Medical University, Dongguan 523808, China
    3Sinan County People's Hospital, Tongren 565100, China
  • Received:2026-04-26 Published:2026-10-01
  • Corresponding author: Wenzhen Wu
  • Supported by:
    Medical Research Fund of Guangdong Province(B2026641)
引用本文:

钟婷婷, 陈梓锋, 杨金鑫, 张少冰, 吴文震. 益生菌水凝胶在龋病防治中的研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(05): 372-382.

Tingting Zhong, Zifeng Chen, Jinxin Yang, Shaobing Zhang, Wenzhen Wu. Research progress of probiotic hydrogels in the prevention and treatment of dental caries[J/OL]. Chinese Journal of Stomatological Research(Electronic Edition), 2026, 20(05): 372-382.

龋病作为全球高发的慢性感染性疾病,其传统预防药物(如抗菌剂和氟化物)存在诱导耐药性与破坏口腔微生态平衡等局限。益生菌"以菌制菌"的微生态调控策略成为防治新思路,但临床现有益生菌产品普遍存在口腔滞留时间短、易被唾液冲刷和难以在牙面有效定植等问题。而水凝胶作为新型递送体系,能高效包载益生菌并实现病灶靶向定植,显著延长作用时间,通过竞争排斥致龋菌、调节pH值、分泌抑菌物及调节免疫等途径发挥作用。本文综述了益生菌防龋水凝胶的研究进展,重点阐述防龋原理、菌株筛选原则、水凝胶设计机制及降解动力学对递送与治疗的调控作用,旨在为龋病的微生态防治与临床转化提供理论参考。

Dental caries is a highly prevalent chronic infectious disease worldwide. However, traditional preventive agents, such as antimicrobials and fluorides, face limitations including the induction of bacterial resistance and disruption of oral microecological balance. Emerging as a novel strategy, microecological regulation using probiotics to "combat bacteria with bacteria" offers a promising alternative for caries prevention. Nevertheless, current clinical probiotic products generally suffer from short retention times in the oral cavity, susceptibility to saliva rinsing, and difficulty in achieving effective colonization on dental surfaces. As an innovative delivery system, hydrogels can efficiently encapsulate probiotics, achieve lesion-targeted colonization, and significantly prolong retention time. These hydrogel systems exert anti-caries effects through competitive exclusion of cariogenic bacteria, pH regulation, secretion of antimicrobial substances, and immune modulation. This article reviews recent research progress on probiotic-loaded anti-caries hydrogels, with a particular focus on the anti-caries mechanisms, principles of strain selection, hydrogel design mechanisms, and the regulatory roles of degradation kinetics in probiotic delivery and therapy. Overall, this review aims to provide a theoretical reference for the microecological prevention and clinical translation of dental caries.

表1 主要防龋益生菌种属及其防龋机制汇总
菌属 代表菌株 拉丁学名(缩写) 核心防龋作用与特点 临床RCT证据
乳杆菌属(核心类群) 罗伊氏乳杆菌 Lactobacillus reuteri(L. reuteri) 有效抑制S. mutans黏附与定植,调节口腔pH值,防龋领域研究与应用最广泛[15],现有证据支持其防龋效果较为明确。 一项针对幼儿的12个月RCT显示,含DSM 17938的滴剂未能降低新发龋齿复发率(两组均为67%)。另有RCT显示可减少S. mutans,但对已形成的龋病无逆转效果[16]。
  植物乳杆菌 Lactiplantibacillus plantarum(L. plantarum) 抑菌活性、口腔定植能力强,安全性高,对S. mutans生物膜具有抑制效果[17],应用潜力大。 目前仅有体外生物膜模型研究证实其抑菌效果。缺乏以S. mutans计数或龋齿发生率为终点的人体RCT。
  干酪乳杆菌 Lactobacillus casei(L. casei) 核心防龋益生菌类群成员,参与口腔微生态调节[8],辅助抑制致龋菌。 有一项RCT显示,含L. casei的酸奶可暂时降低唾液中S. mutans水平,但效果在停止摄入后2周即消失。未评估龋齿终点[18]。
  嗜酸乳杆菌 Lactobacillus acidophilus(L. acidophilus) 乳杆菌属核心防龋菌株,助力维持口腔微生态平衡[19]。 绝大多数研究为含多种菌株的复合益生菌产品(常与L. rhamnosus、双歧杆菌联用),无法单独归因于L. acidophilus。单独使用的RCT非常稀缺。
双歧杆菌属 婴儿双歧杆菌 Bifidobacterium infantis(B. infantis) 通过竞争性排斥抑制致龋菌[20],调节口腔微生态与宿主免疫,安全性高,适合防龋产品开发。 目前所有RCT均针对肠道健康或过敏性疾病。在口腔防龋领域,没有任何以口腔菌群或龋齿为终点的人体研究。
  长双歧杆菌 Bifidobacterium longum(B. longum) 同上,竞争性抑制致龋菌生长,调节免疫与微生态[21],辅助防龋。 与B. infantis类似,现有RCT集中于肠道和免疫调节。缺乏口腔防龋的人体研究证据。
链球菌属(口腔固有有益菌) 唾液链球菌 Streptococcus salivarius(S. salivarius) 口腔天然有益菌,分泌抗菌物质抑制S. mutans,维持微生态稳态[22],定植与相容性好。 一项RCT显示M18+K12组合反而使S. mutans显著增加(750→1 700 CFU/mL)。另有两项RCT分别显示K12或M18单用可减少S. mutans。提示特定组合可能有害[23]。
血链球菌 Streptococcus sanguinis(S. sanguinis) 口腔固有有益菌,抑制致龋菌生长[24],参与维持口腔微生态平衡。 所有研究均为观察性横断面研究,发现龋活跃者体内S. sanguinis丰度较低。没有任何以口服该菌株作为干预手段的RCT。
其他潜在防龋益生菌 鼠李糖乳杆菌 Lacticaseibacillus rhamnosus(L. rhamnosus) 可减少致龋菌数量、调节唾液pH、降低龋病活性[25],为重要候选菌株。 一项针对幼儿的6个月RCT显示,L. rhamnosus SD11可显著降低龋齿进展率(3.48% vs. 4.55%),同时减少S. mutans。另有短期RCT证实可抑制致龋菌[26]。
表2 不同响应类型防龋机制对比表
图1 益生菌水凝胶的防龋机制示意图 HAP:羟基磷灰石。
[1]
Spatafora G,Li Y,He X,et al. The evolving microbiome of dental caries[J]. Microorganisms,2024,12(1):121. DOI:10.3390/microorganisms12010121.
[2]
Celik Z C,Cakiris A,Abaci N,et al. The complex microbiome of caries-active and caries-free supragingival plaques in permanent dentition[J]. Niger J Clin Pract,2021,24(10):1535-1540. DOI:10.4103/njcp.njcp_49_21.
[3]
Klein M I,Hwang G,Santos P H,et al. Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms[J]. Front Cell Infect Microbiol,2015(5):10. DOI:10.3389/fcimb.2015.00010.
[4]
Banakar M,Pourhajibagher M,Etemad-Moghadam S,et al. Antimicrobial effects of postbiotic mediators derived from Lactobacillus rhamnosus GG and Lactobacillus reuteri on Streptococcus mutans[J]. Front Biosci(Landmark Ed),2023,28(5):88. DOI:10.31083/j.fbl2805088.
[5]
Hasslöf P,Stecksén-Blicks C. Chapter 10:Probiotic bacteria and dental caries[J]. Monogr Oral Sci,2020(28):99-107. DOI:10.1159/000455377.
[6]
Yadav A A,Mujawar S S,Shinde N A,et al. A multifunctional tragacanth gum-chitosan hydrogel loaded with manganese ferrite nanoparticles for dental caries prevention and remineralization[J]. Int J Biol Macromol,2025,322(Pt 3):146886. DOI:10.1016/j.ijbiomac.2025.146886.
[7]
刘亚琪,马其钊,蒙明梅,等.天然产物在维护口腔微生态平衡中的研究进展[J].四川大学学报(医学版),2026,57(1):49-55. DOI:10.12182/20260160509.
[8]
Rajasekaran J J,Krishnamoorthy H K,Bosco J,et al. Oral microbiome:A review of its impact on oral and systemic health[J]. Microorganisms,2024,12(9):1797. DOI:10.3390/microorganisms12091797.
[9]
Liu R,Liu Y,Yi J,et al. Imbalance of oral microbiome homeostasis:The relationship between microbiota and the occurrence of dental caries[J]. BMC Microbiology,2025,25(1):46. DOI:10.1186/s12866-025-03762-6.
[10]
Bartsch S,Kohnert E,Kreutz C,et al. Chlorhexidine digluconate mouthwash alters the oral microbial composition and affects the prevalence of antimicrobial resistance genes[J]. Front Microbiol,2024(15):1429692. DOI:10.3389/fmicb.2024.1429692.
[11]
Yeh C H,Wang Y L,Vo T T T,et al. Fluoride in dental caries prevention and treatment:Mechanisms,clinical evidence,and public health perspectives[J]. Healthcare(Basel),2025,13(17):2246. DOI:10.3390/healthcare13172246.
[12]
孟楠.益生菌预防学龄前儿童龋病疗效的系统评价与Meta分析[D].唐山:华北理工大学,2023. DOI:10.27108/d.cnki.ghelu.2023.001128.
[13]
Chen Y,Hao Y,Chen J,et al. Lacticaseibacillus rhamnosus inhibits the development of dental caries in rat caries model and in vitro[J]. J Dent,2024,149(10):105278. DOI:10.1016/j.jdent.2024.105278.
[14]
周小佩.初乳口腔免疫疗法联合益生菌对早产儿胃肠道功能及肠道菌群的影响观察[J].哈尔滨医药,2023,43(3):38-40. DOI:10.3969/j.issn.1001-8131.2023.03.014.
[15]
Félix-Sicairos B K,Martinez-Martinez R E,Aranda-Romo S,et al. Limosilactobacillus reuteri and its probiotic potential against cariogenic bacteria[J]. Microbiol Res,2024,15(3):1178-1188. DOI:10.3390/microbiolres15030079.
[16]
Hasslöf P,Granqvist L,Stecksén-Blicks C,et al. Prevention of recurrent childhood caries with probiotic supplements:A randomized controlled trial with a 12-month follow-up[J]. Probiotics Antimicrob Proteins,2022,14(2):384-390. DOI:10.1007/s12602-022-09913-9.
[17]
赵忠情.口腔益生乳酸菌的筛选及其对变异链球菌生物膜抑制作用研究[D].石家庄:河北科技大学,2022. DOI:10.27107/d.cnki.ghbku.2022.000920.
[18]
Pørksen C J,Keller M K,Damholt A,et al. The effect of a lozenge combining prebiotic arginine and probiotics on caries increment in children during 10-12 months,a randomized clinical trial[J]. J Dent,2023(135):104599. DOI:10.1016/j.jdent.2023.104599.
[19]
热依拉·艾克兰木,热娜古力·阿不都为力,郭涛,等.益生菌调控联合光动力疗法在种植体周围炎中的应用效果及微生物生态重建分析[J].川北医学院学报,2025,40(8):991-996. DOI:10.3969/j.issn.1005-3697.2025.08.007.
[20]
孙婧宇.益生菌制剂对重度低龄儿童龋防龋作用的研究[D].云南:昆明医科大学,2019. DOI:10.27202/d.cnki.gkmyc.2019.000579.
[21]
黄秋幸,蓝素桂,廖秋眉,等.后生元工艺研究进展及产品开发现状[J/OL].食品与发酵工业,2026:1-13. [2026-04-20].

URL    
[22]
尚骁迪,王珍,葛少华.口腔异味的微生物群驱动机制及干预策略的研究进展[J].四川大学学报(医学版),2026,57(1):37-43. DOI:10.12182/20260160602.
[23]
Nilchian F,Esrafili M,Hosseini N. Evaluation of the effects of Streptococcus salivarius M18 and K12 probiotic bacteria on the Streptococcus mutans in saliva:A randomized clinical trial[J]. Dent Res J,2024,21(1):39. DOI:10.4103/drj.drj_54_24.
[24]
张梦碟. mubR在变异链球菌与血链球菌竞争中的作用研究[D].成都:四川大学,2023. DOI:10.26914/c.cnkihy.2023.092233.
[25]
杜岚.嗜酸乳杆菌外膜包覆纳米颗粒对变异链球菌黏附因子的捕获研究[D].重庆:重庆医科大学,2025. DOI:10.27674/d.cnki.gcyku.2025.000350.
[26]
Bolla V L,Reddy M S,Srinivas N,et al. Investigation and comparison of the effects of two probiotic bacteria,and in reducing mutans streptococci levels in the saliva of children[J]. Ann Afr Med,2022,21(4):395-402. DOI:10.4103/aam.aam_133_21.
[27]
Bosch M,Nart J,Audivert S,et al. Isolation and characterization of probiotic strains for improving oral health[J]. Arch Oral Biol,2012,57(5):539-549. DOI:10.1016/j.archoralbio.2011.10.006.
[28]
宁亚维,赵忠情,孙颖,等.抗龋齿口腔益生乳酸菌的筛选[J].食品科学,2023,44(10):195-204. DOI:10.7506/spkx1002-6630-20220613-133.
[29]
Beattie E R. Probiotics for oral health:A critical evaluation of bacterial strains[J]. Front Microbiol,2024(15):1430810. DOI:10.3389/fmicb.2024.1430810.
[30]
Inchingolo A D,Inchingolo A M,Palumbo I,et al. The role of probiotics in preventing dental caries:A systematic review of clinical evidence[J]. Front Oral Health,2025(6):1720036. DOI:10.3389/froh.2025.1720036.
[31]
蔡祉恒,杜嵘,朱亚琴.益生菌及靶向递送体系在口腔疾病防治中的研究进展[J].口腔材料器械杂志,2025,34(3):174-179. DOI:10.11752/j.kqcl.2025.03.09.
[32]
Ribeiro F C,Junqueira J C,Dos Santos J D,et al. Development of probiotic formulations for oral candidiasis prevention:Gellan gum as a carrier to deliver Lactobacillus paracasei 28.4[J]. Antimicrob Agents Chemother,2020,64(6):e02323-19. DOI:10.1128/aac.02323-19.
[33]
Nezamdoost-Sani N,Khaledabad M A,Amiri S,et al. A comprehensive review on the utilization of biopolymer hydrogels to encapsulate and protect probiotics in foods[J]. Int J Biol Macromol,2024,254(Pt 2):127907. DOI:10.1016/j.ijbiomac.2023.127907.
[34]
Rovelli R,Cecchini B,Zavagna L,et al. Emerging multiscale biofabrication approaches for bacteriotherapy[J]. Molecules,2024,29(2):533. DOI:10.3390/molecules29020533.
[35]
Chen Y,Lin S,Huang X,et al. From biofilm control to biomimetic remineralization:Hydrogels in prevention and treatment of dental caries[J]. Front Cell Infect Microbiol,2025(15):1663563. DOI:10.3389/fcimb.2025.1663563.
[36]
Zhou W,Tian M,Wang H,et al. Integration of metal-organic frameworks into hydrogels:Optimizing their properties and applications[J]. Zeitschrift für anorganische und allgemeine Chemie,2024,650(24):e202400157. DOI:10.1002/zaac.202400157.
[37]
Ways T M M,Lau W M,Khutoryanskiy V V. Chitosan and its derivatives for application in mucoadhesive drug delivery systems[J]. Polymers(Basel),2018,10(3):267. DOI:10.3390/polym10030267.
[38]
Zhang F,Zheng X,Ma Y,et al. Sodium alginate/low methoxyl pectin composite hydrogel beads prepared via gas-shearing technology for enhancing the colon-targeted delivery of probiotics and modulating gut microbiota[J]. Int J Biol Macromol,2025,300(17):140375. DOI:10.1016/j.ijbiomac.2025.140375.
[39]
高楚琪,赵梓墨,黄羽彤,等.益生菌-水凝胶递送系统的研究进展及应用潜力[J].微生物学报,2022,62(3):806-823. DOI:10.13343/j.cnki.wsxb.20210488.
[40]
王宇洁,邹杰林,蔡明轩,等.壳聚糖基水凝胶在口腔组织工程中的应用[J].中南大学学报(医学版),2023,48(1):138-147. DOI:10.11817/j.issn.1672-7347.2023.220370.
[41]
Chelu M,Popa M,Moreno C M J. Next-generation natural hydrogels in oral tissue engineering[J]. Pharmaceutics,2025,17(10):1256-1256. DOI:10.3390/pharmaceutics17101256.
[42]
Song J,Sun H,Pan L,et al. Metal-organic cages based catalytic hybrid hydrogels for enhanced wound healing:Antibacterial and regenerative effects of Zr-MOC/chitosan composites hydrogel[J]. Int J Biol Macromol,2025(301):139851. DOI:10.1016/j.ijbiomac.2025.139851.
[43]
Rafiee A,Mozafari N,Fekri N,et al. Preparation and characterization of a nanohydroxyapatite and sodium fluoride loaded chitosan-based in situ forming gel for enamel biomineralization[J]. Heliyon,2024,10(2):e24217. DOI:10.1016/j.heliyon.2024.e24217.
[44]
Chen G,Wamg F,Zhang X,et al. Living microecological hydrogels for wound healing[J]. Sci Adv,2023,9(21):eadg3478. DOI:10.1126/sciadv.adg3478.
[45]
Mereness JA,Piraino L,Chen CY,et al. Slow hydrogel matrix degradation enhances salivary gland mimetic phenotype[J]. Acta Biomater,2023,166(12):187-200. DOI:10.1016/j.actbio.2023.05.005.
[46]
Yu Q,Jun T,Siyi K,et al. SrCuSi4 O10/GelMA composite hydrogel-mediated vital pulp therapy:Integrating antibacterial property and enhanced pulp regeneration activity[J]. Adv Healthc Mater,2023,12(24):e2300546. DOI:10.1002/adhm.202300546.
[47]
Liang J,Wang Z,Poot A A,et al. Enzymatic post-crosslinking of printed hydrogels of methacrylated gelatin and tyramine-conjugated 8-arm poly(ethylene glycol)to prepare interpenetrating 3D network structures[J]. Int J Bioprint,2023,9(5):750. DOI:10.18063/ijb.750.
[48]
Ming Z,Han L,Bao M,et al. Living bacterial hydrogels for accelerated infected wound healing[J]. Adv Sci(Weinh),2021,8(24):e2102545. DOI:10.1002/advs.202102545.
[49]
Chi C,Li R,Zhao Y,et al. Construction of chitosan/genipin-based bioactive hydrogels with antioxidant and antibacterial effects for infection management and chronic wound healing[J]. J Appl Polym Sci,2025,142(42):e57633. DOI:10.1002/app.57633.
[50]
de Alvarenga J A,de Barros P P,de Camargo Ribeiro F,et al. Probiotic effects of lactobacillus paracasei 28.4 to inhibit Streptococcus mutans in a gellan-based formulation[J]. Probiotics Antimicrob Proteins,2021,13(2):506-517. DOI:10.1007/s12602-020-09712-0.
[51]
Wang Y,Liang Z,Liu X,et al. Research progress on preparation of polysaccharide-based probiotic microcapsules and their application in food[J]. Food Chemistry,2026,508(11):148328. DOI:10.1016/j.foodchem.2026.148328.
[52]
Zhang X,Xiang J,Hong Y,et al. Recent advances in design strategies of tough hydrogels[J]. Macromol Rapid Commun,2022,43(15):e2200075. DOI:10.1002/marc.202200075.
[53]
Tsou C H,Shui Y S,Du J,et al. Characterization and morphology of nanocomposite hydrogels with a 3D network structure prepared using attapulgite-enhanced polyvinyl alcohol[J]. Polymers (Basel),2023,15(11):2535. DOI:10.3390/polym15112535.
[54]
Li M F,Cui H L,Lou W Y. Millettia speciosa Champ cellulose-based hydrogel as a novel delivery system for Lactobacillus paracasei:Its relationship to structure,encapsulation and controlled release[J]. Carbohydr Polym,2023,316(18):121034. DOI:10.1016/j.carbpol.2023.121034.
[55]
Su C,Liu J,Yang Z,et al. UV-mediated synthesis of carboxymethyl cellulose/poly-N-isopropylacrylamide composite hydrogels with triple stimuli-responsive swelling performances[J]. Int J Biol Macromol,2020,161(20):1140-1148. DOI:10.1016/j.ijbiomac.2020.06.094.
[56]
Qu S,Ma X,Yu S,et al. Chitosan as a biomaterial for the prevention and treatment of dental caries:Antibacterial effect,biomimetic mineralization,and drug delivery[J]. Front Bioeng Biotechnol,2023(11):1234758. DOI:10.3389/fbioe.2023.1234758.
[57]
Geng Z,Ji Y,Yu S,et al. Preparation and characterization of a dual cross-linking injectable hydrogel based on sodium alginate and chitosan quaternary ammonium salt[J]. Carbohydr Res,2021,507(9):108389. DOI:10.1016/j.carres.2021.108389.
[58]
Hoffmann A,Fischer J T,Daniels R. Development of probiotic orodispersible tablets using mucoadhesive polymers for buccal mucoadhesion[J]. Drug Dev Ind Pharm,2020,46(11):1753-1762. DOI:10.1080/03639045.2020.1831013.
[59]
Dou X,Li G,Wang S,et al. Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing[J]. Int J Biol Macromol,2023,244(21):125273. DOI:10.1016/j.ijbiomac.2023.125273.
[60]
杨少康,李玲利,王润泽,等.益生菌-水凝胶协同递送系统的研究进展与AI+设计发展新趋势[J].河南工业大学学报(自然科学版),2026,47(1):130-140. DOI:10.16433/j.1673-2383.202504250001.
[61]
Quan Y,Shao H,Wang N,et al. Microenvironment-sensitive hydrogels as promising drug delivery systems for co-encapsulating microbial homeostasis probiotics and anti-inflammatory drugs to treat periodontitis[J]. Mater Today Bio,2025(32):101711. DOI:10.1016/j.mtbio.2025.101711.
[62]
Raknam P,Balekar N,Teanpaisan R,et al. Thermoresponsive sol-gel containing probiotic's cell free supernatant for dental caries prophylaxis[J]. J Oral Microbiol,2022,14(1):2012390. DOI:10.1080/20002297.2021.2012390.
[63]
Guo J,Lei W,Li B,et al. Injectable living hydrogel as engineered biotherapeutic to promote tooth-extraction wound healing and alveolar bone regeneration[J]. Bioact Mater,2026(59):355-369. DOI:10.1016/j.bioactmat.2025.12.051.
[64]
Chau A L,Getty P T,Rhode A R,et al. Superlubricity of pH-responsive hydrogels in extreme environments[J]. Front Chem,2022(10):891519. DOI:10.3389/fchem.2022.891519.
[65]
Liu B,Li J,Zhang Z,et al. pH responsive antibacterial hydrogel utilizing catechol-boronate complexation chemistry[J]. Chem Eng J,2022,441(15):135808. DOI:10.1016/j.cej.2022.135808.
[66]
Richa,Roy Choudhury A. pH mediated rheological modulation of chitosan hydrogels[J]. Int J Biol Macromol,2020,156(15):591-597. DOI:10.1016/j.ijbiomac.2020.04.049.
[67]
Bhattacharya S,Baidya S. Viability preservation of probiotic bacteria encapsulated in pectin-reinforced pH-responsive composite alginate hydrogel matrix as the synbiotic delivery system[J]. Probiotics Antimicrob Proteins,2025,18(2):1-15. DOI:10.1007/s12602-025-10661-9.
[68]
Liu X,Zhang Y,Liu Y,et al. Injectable,self-healable and antibacterial multi-responsive tunicate cellulose nanocrystals strengthened supramolecular hydrogels for wound dressings[J]. Int J Biol Macromol,2023,240(17):124365. DOI:10.1016/j.ijbiomac.2023.124365.
[69]
Mahboubian A,Vllasaliu D,Dorkoosh F A,et al. Temperature responsive methylcellulose-hyaluronic hydrogel as a 3D cell culture matrix[J]. Biomacromolecules,2020,21(12):4737-4746. DOI:10.1021/acs.biomac.0c00906.
[70]
Zanbili F,Poursattar Marjani A,Mahmoudian M. Multi-responsive,room-temperature self-healing salep-based nanocomposite hydrogels with enhanced mechanical performance as smart biomaterial[J]. Sci Rep,2026,16(1):7090. DOI:10.1038/s41598-026-38127-0.
[71]
He Y,Haidari H,Le T N,et al. Dual pH and temperature-responsive hydrogel delivery system containing "intelligent particles" for the treatment of dental caries:An in vitro study[J]. J Dent,2025,165(2):106284. DOI:10.1016/j.jdent.2025.106284.
[72]
Luo R,Xiang X,Jiao Q,et al. Photoresponsive hydrogels for tissue engineering[J]. ACS Biomater Sci Eng,2024,10(6):3612-3630. DOI:10.1021/acsbiomaterials.4c00314.
[73]
Chau A L,Karnaukh K M,Maskiewicz I,et al. Photoresponsive hydrogel friction[J]. Soft Matter,2024,20(36):7227-7236. DOI:10.1039/d4sm00677a.
[74]
Rehor I,Maslen C,Moerman P G,et al. Photoresponsive hydrogel microcrawlers exploit friction hysteresis to crawl by reciprocal actuation[J]. Soft Robot,2020,8(1):10-18. DOI:10.1089/soro.2019.0169.
[75]
Park K Y,Odde D J,Distefano M D. Photoresponsive hydrogels for studying mechanotransduction of cells[M]//Zaidel-Bar R. Mechanobiology:Methods and protocols. Methods in molecular biology,2023(2600):133-153. DOI:10.1007/978-1-0716-2851-5_9.
[76]
Zhang H,Zhong J,Zhang Z,et al. Photoresponsive hexaaryl biimidazole-crosslinked hydrogels:From synthesis to diverse applications[J]. Angew Chem Int Ed Engl,2025,64(52):e20013. DOI:10.1002/anie.202520013.
[77]
Marcin S. Enzyme-responsive hydrogels as potential drug delivery systems:State of knowledge and future prospects[J]. Int J Molr Sci,2022,23(8):4421. DOI:10.3390/ijms23084421.
[78]
Carlini A S,Cassidy M F,Gianneschi N C. Hydrogel formation with enzyme-responsive cyclic peptides[M]. Coppock M B,Winton A J. Peptide Macrocycles:Methods and Protocols. Methods in Molecular Biology,2022(2371):427-448. DOI:10.1007/978-1-0716-1689-5_23.
[79]
Yang X,Nie W,Wang C,et al. Microfluidic-based multifunctional microspheres for enhanced oral co-delivery of probiotics and postbiotics[J]. Biomaterials,2024,308(5):122564. DOI:10.1016/j.biomaterials.2024.122564.
[80]
Li B Y,Lin T Y,Lai Y J,et al. Engineering multiresponsive alginate/PNIPAM/carbon nanotube nanocomposite hydrogels as on-demand drug delivery platforms[J]. Small,2025,21(12):e2407420. DOI:0.1002/smll.202407420.
[81]
Wei X,Wu Q,Chen L,et al. Remotely controlled light/electric/magnetic multiresponsive hydrogel for fast actuations[J]. ACS Appl Mater Interfaces,2023,15(7):10030-10043. DOI:10.1021/acsami.2c22831.
[82]
曾欣,刘帆.水凝胶载药系统在牙周炎治疗中的研究进展[J].四川大学学报(医学版),2023,54(4):721-725. DOI:10.12182/20230760203.
[83]
候冰娜,倪凯,沈慧玲,等.自修复氧化海藻酸钠-羧甲基壳聚糖水凝胶的制备及药物缓释性能[J].复合材料学报,2022,39(1):250-257. DOI:10.13801/j.cnki.fhclxb.20210518.005.
[84]
Gould M L,Downes N J,Woolley A G,et al. Harnessing the regenerative potential of purified bovine dental pulp and dentin extracellular matrices in a chitosan/alginate hydrogel[J]. Macromol Biosci,2024,24(11):e2400254. DOI:10.1002/mabi.202400254.
[85]
Dimmitt N H,Lin C C. Hydrolytic degradation of PEG-based thiol-norbornene hydrogels enables multi-modal controlled release[J]. J Mater Chem B,2025,13(42):13781-13793. DOI:10.1039/d5tb01524c.
[86]
del Pozo M L,Aguanell A,García-Junceda E,et al. Lysozyme-responsive hydrogels of chitosan-streptomycin conjugates for the on-demand release of biofilm-dispersing enzymes for the efficient eradication of oral biofilms[J]. Chem Mater,2024,36(19):9860-9873. DOI:10.1021/acs.chemmater.4c02014.
[87]
Gao Y,Wang P,Huang S,et al. Antibacterial reuterin as a multifunctional crosslinker for constructing chitosan-based hydrogels to promote infected wound healing[J]. Int J Biol Macromol,2025,316(Pt 1):144494. DOI:10.1016/j.ijbiomac.2025.144494.
[88]
Nizami M Z I,Chu S,Chu S,et al. Probiotics for caries prevention:A narrative review[J]. J Appl Biomater Funct Mater,2025,23(1):22808000251376427. DOI:10.1177/22808000251376427.
[89]
陈露,展平,宋勇,等.基于水凝胶的干扰素基因刺激因子激动剂递送系统在肿瘤治疗中的应用进展[J].生物工程学报,2026,42(5):2023-2036. DOI:10.13345/j.cjb.250822.
[90]
Mahdizade Ari M,Mirkalantari S,Darban-Sarokhalil D,et al. Investigating the antimicrobial and anti-inflammatory effects of Lactobacillus and Bifidobacterium spp. on cariogenic and periodontitis pathogens[J]. Front Microbiol,2024,15(1):1383959. DOI:10.3389/fmicb.2024.1383959.
[91]
王玉雪,周歆,郑钧元,等.人β-防御素3水凝胶治疗大鼠牙周炎[J].中国组织工程研究,2024,28(17):2690-2695. DOI:10.12307/2024.448.
[92]
Cao Z,Luo Y,Li Z,et al. Antibacterial hybrid hydrogels[J]. Macromol Biosci,2021,21(1):e2000252. DOI:10.1002/mabi.202000252.
[93]
Wang Y,Qu Y,Liu X,et al. Dual-functional probiotic hydrogel with puerarin integration for microbiota-neuroimmune regulation in antibiotic-free periodontitis therapy[J]. Bioact Mater,2025,53(11):72-83. DOI:10.1016/j.bioactmat.2025.07.004.
[94]
董羽嘉,黄颖,张馨月,等. pH响应性壳聚糖药物递送系统响应机制及应用进展[J].生物工程学报,2026,42(5):1996-2010. DOI:10.13345/j.cjb.250899.
[95]
Zhou L,Liu Q,Fang Z,et al. Targeted antimicrobial self-assembly peptide hydrogel with in situ bio-mimic remineralization for caries management[J]. Bioact Mater,2025,44(2):428-446. DOI:10.1016/j.bioactmat.2024.10.022.
[96]
Wang L,Wei X,Duan C,et al. Bone marrow mesenchymal stem cell sheets with high expression of hBD3 and CTGF promote periodontal regeneration[J]. Biomater Adv,2022,133(1):112657. DOI:10.1016/j.msec.2022.112657.
[97]
Sardar D,Morol I,Bari J,et al. Optimization of cryoprotectants and storage temperatures for preserving viability and probiotic properties of lyophilized bacterial strains from chicken gut[J]. PLoS One,2025,20(7):e0328216. DOI:10.1371/journal.pone.0328216.
[98]
Cruz M G D,Silva A M S D,Prada-Mejia K D,et al. Skim milk as a multifunctional cryoprotectant for fish probiotic Enterococcus spp:Impact on viability during lyophilization and long-term storage[J]. Microorganisms,2025,13(11):2486. DOI:10.3390/microorganisms13112486.
[99]
Onwe R O,Onwosi C O,Ezugworie F N,et al. Microbial trehalose boosts the ecological fitness of biocontrol agents,the viability of probiotics during long-term storage and plants tolerance to environmental-driven abiotic stress[J]. Sci Total Environ,2022,806(Pt 1):150432. DOI:10.1016/j.scitotenv.2021.150432.
[100]
Liu H,Shen Y. Environmental stimuli-responsive hydrogels in endodontics:Advances and perspectives[J]. Int Endod J,2025,58(5):674-684. DOI:10.1111/iej.14208.
[101]
Arun B K,Nisha P,Plessas S,et al. Editorial:Probiotics for global health:Advances,applications and challenges[J]. Front Microbiol,2025(16):1697319. DOI:10.3389/fmicb.2025.1697319.
[102]
Liu B,Chen K. Advances in hydrogel-based drug delivery systems[J]. Gels,2024,10(4):262. DOI:10.3390/gels10040262.
[103]
Kumar P,Goel A,Dash B,et al. Innovations in drug delivery systems for biologics:Enhancing stability and targeted delivery for next-generation therapeutics[J]. Zhongguo Ying Yong Sheng Li Xue Za Zhi,2025(41):e20250001. DOI:10.62958/j.cjap.2025.001.
[104]
Garshasbi H,Salehi S,Naghib S M,et al. Stimuli-responsive injectable chitosan-based hydrogels for controlled drug delivery systems[J]. Front Bioeng Biotechnol,2023(10):1126774. DOI:10.3389/fbioe.2022.1126774.
[105]
Alforaidi S,Bresin A,Almosa N,et al. Oral Colonisation after the administration of drops containing Lactobacillus reuteri[J]. Oral Health Prev Dent,2020,18(4):1017-1023. DOI:10.3290/j.ohpd.a45523.
[106]
Vestman R N,Chen T,Holgerson L P,et al. Oral Microbiota shift after 12-week supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289;A randomized control trial[J]. PLoS One,2017,10(5):e0125812. DOI:10.1371/journal.pone.0125812.
[107]
Wang Y,Tang Y,Huang Q,et al. Engineered Lactobacillus reuteri for scavenging reactive oxygen species and modulating oral microflora in periodontitis therapy[J]. Int J Oral Sci,2026,18(1):16. DOI:10.1038/s41368-025-00418-z.
[108]
Maukonen J,Mättö J,Suihko M L,et al. Intra-individual diversity and similarity of salivary and faecal microbiota[J]. J Med Microbiol,2008,57(Pt 12):1560-1568. DOI:10.1099/jmm.0.47352-0.
[109]
Lundtorp-Olsen C,Enevold C,Twetman S,et al. Probiotics do not alter the long-term stability of the supragingival microbiota in healthy subjects:A randomized controlled trial[J]. Pathogens,2021,10(4):391. DOI:10.3390/pathogens10040391.
[110]
Pham L C,van Spanning R J,Röling W F,et al. Effects of probiotic Lactobacillus salivarius W24 on the compositional stability of oral microbial communities[J]. Arch Oral Biol,2009,54(2):132-137. DOI:10.1016/j.archoralbio.2008.09.007
[111]
Yersin S,Gody C J,Mazel F,et al. Strain-level translocation and enrichment dynamics of oral bacteria in the lower gastrointestinal tract of stunted children[J]. Gut Microbes,2026,18(1):2653550. DOI:10.1080/19490976.2026.2653550.
[112]
陈一鸣,刘畅,郭晓奎.益生菌候选菌株的耐药性传播风险评估方法的研究进展[J].中国微生态学杂志,2025,37(12):1475-1479. DOI:10.13381/j.cnki.cjm.202512016.
[113]
Jansen P M,Abdelbary M M H,Conrads G. A concerted probiotic activity to inhibit periodontitis-associated bacteria[J]. PLoS One,2021,16(3):e0248308. DOI:10.1371/journal.pone.0248308.
[114]
Kanganwiro M,Saltiel H,Winschau Z V F,et al. Recent advances in genetic tools for engineering probiotic lactic acid bacteria[J]. Biosci Rep,2023,43(1):BSR20211299. DOI:10.1042/BSR20211299.
[115]
Dai C,Shi Z,Xu Y,et al. Wearable multifunctional hydrogel for oral microenvironment visualized sensing coupled with sonodynamic bacterial elimination and tooth whitening[J]. Adv Healthc Mater,2025,14(1):e2401269. DOI:10.1002/adhm.202401269.
[116]
Peng Z,Yang L,Wei Z,et al. Lactobacillus plantarum NCU001774 microcapsules target and inhibit cariogenic Streptococcus mutans[J]. Food Biosci,2024,59(3):104010. DOI:10.1016/j.fbio.2024.104010.
[117]
Zhu J,Zhang M,Qiu R,et al. Hagfish-inspired hydrogel for root caries:A multifunctional approach including immediate protection,antimicrobial phototherapy,and remineralization[J]. Acta Biomater,2024,188(16):117-137. DOI:10.1016/j.actbio.2024.09.014.
[118]
Lopes P C,Gomes A T P C,Mendes K,et al. Unlocking the potential of probiotic administration in caries management:A systematic review[J]. BMC Oral Health,2024,24(1):216. DOI:10.1186/s12903-024-03893-8.
[119]
Zhang S,Wang H,Liu F,et al. Artificial intelligence-enabled hydrogels:Innovations and applications[J]. J Mater Chem B,2025,13(46):14967-14981. DOI:10.1039/d5tb01944c.
[120]
Cadamuro F,Piazzoni M,Gamba E,et al. Artificial Intelligence tool for prediction of ECM mimics hydrogel formulations via click chemistry[J]. Biomater Adv,2025(175):214323. DOI:10.1016/j.bioadv.2025.214323.
[121]
Martineau R L,Bayles A V,Hung C S,et al. Engineering gelation kinetics in living silk hydrogels by differential dynamic microscopy microrheology and machine learning[J]. Advd Biol (Weinh),2021,6(1):e2101070. DOI:10.1002/adbi.202101070.
[122]
Susan W,Francesca C,Molly E,et al. Optimization of probiotic therapeutics using machine learning in an artificial human gastrointestinal tract[J]. Sci Rep,2021,11(1):1067-1067. DOI:10.1038/s41598-020-79947-y.
[123]
Wu S,Feng T,Tang W,et al. metaProbiotics:A tool for mining probiotic from metagenomic binning data based on a language model[J]. Brief Bioinform,2024,25(2):bbae085. DOI:10.1093/bib/bbae085.
[124]
Yadav S,Shivangi,Yashika,et al. Framework of spatiotemporal AI models for colon microbiota-nanoparticle dynamics[J]. Ther Deliv,2026,17(5):377-381. DOI:10.1080/20415990.2026.2671598.
[125]
Robin V,Wim T,Maria CL,et al. Probiotics for maintaining oral health during fixed orthodontic treatment:A systematic review and Meta-analysis[J]. Int J Dent Hyg,2024,23(1):100-113. DOI:10.1111/idh.12821.
[126]
Marie O,Bing S F,Laëtitia P L,et al. Tolerance to intraoral biofilms and their effectiveness in improving mouth dryness and modifying oral microbiota in patients with primary Sjögren's syndrome:"Predelfi study"[J]. Front Microbiol,2023(14):1071683. DOI:10.3389/fmicb.2023.1071683.
[1] 黄宇阳, 李永生, 罗程, 何奕君, 潘骞. 微孔水凝胶与双细胞因子协同促软骨分化的实验研究[J/OL]. 中华关节外科杂志(电子版), 2025, 19(05): 560-569.
[2] 王玺玉, 赵俊杰, 黄鹏飞, 张兆坤, 赵宇昊, 赵海燕. 基质金属蛋白酶响应性水凝胶在骨关节炎的应用[J/OL]. 中华关节外科杂志(电子版), 2025, 19(01): 76-81.
[3] 陈强, 曹胜军, 李全, 赵翠娟. 益生菌在烧伤创面愈合中作用机制的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2026, 21(01): 63-68.
[4] 刘昌玲, 张金丽, 张志, 李孝建, 汤文彬, 胡逸萍, 陈宾, 谢晓娜. 负载人脂肪干细胞外泌体的甲基丙烯酰化明胶水凝胶对人皮肤成纤维细胞增殖和迁移的影响[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(06): 517-525.
[5] 关丁丁, 李伟, 孔维诗, 包郁露, 孙瑜. 负载干细胞的光交联蛋白基水凝胶在组织工程中应用的研究进展[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(05): 447-452.
[6] 张文青, 强茹月, 裴丹丹, 张辉. 不同杨氏模量聚丙烯酰胺水凝胶模型的构建及其对小鼠骨髓间充质干细胞行为的影响[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(04): 304-310.
[7] 李宗泰, 王焱. 压电水凝胶:口腔组织再生修复的新策略[J/OL]. 中华口腔医学研究杂志(电子版), 2026, 20(04): 245-252.
[8] 王阅, 杨园梦, 何德亿, 孟雯, 陈昕煜, 李飞, 卢展民, 陆海霞. 基于口腔微生态的龋病防治研究进展[J/OL]. 中华口腔医学研究杂志(电子版), 2024, 18(06): 391-396.
[9] 梁瑶瑶, 邬绿莹, 陈津. 负载干细胞外泌体水凝胶治疗糖尿病足溃疡的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(02): 112-119.
[10] 苟亚妮, 申群斌, 张丽, 卢佳佳. 幽门螺杆菌根除治疗与肠道菌群失调的互作机制、挑战与干预策略探究[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(04): 359-363.
[11] 朱万涌, 王乐, 徐越, 王新军, 叶晨, 李宁, 陈启仪, 李龙. 肠道菌群失衡与功能性肠病:从机制探讨到肠菌移植疗法[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(02): 142-147.
[12] 高文勇, 汤灿, 严友杰, 魏民, 张恒柱, 王晓东. 光固化GelMA水凝胶联合线粒体移植促进脊髓损伤修复的研究[J/OL]. 中华神经创伤外科电子杂志, 2025, 11(06): 380-389.
[13] 孙明策, 韩世焕. 海藻酸盐水凝胶支架在颅骨缺损修复中的应用进展[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 310-314.
[14] 排尔哈提·亚生, 陆云, 王磊磊, 李哲, 宋兴华, 盛杰. 光交联功能化水凝胶促进骨修复研究进展[J/OL]. 中华老年骨科与康复电子杂志, 2026, 12(04): 243-249.
[15] 史若琳, 何凡. 微生物-肠-脑轴在注意缺陷多动障碍中的研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(11): 860-865.
阅读次数
全文


摘要


AI
小
编
AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?