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北京大学学报（医学版） ›› 2025, Vol. 57 ›› Issue (5): 841-846. doi: 10.19723/j.issn.1671-167X.2025.05.005

• 工作综述 • 上一篇    下一篇

基于微环境和干细胞调控的牙周组织再生关键技术的建立与应用

马保金1,2, 李建华1,3, 桑元华4, 于洋1, 仇吉川4, 邵金龙1, 李凯3, 刘世岳1, 杜密1, 商玲玲1, 葛少华1,*()   

  1. 1. 山东大学口腔医学院·口腔医院牙周病科, 济南 250012
    2. 山东大学口腔医学院·口腔医院组织工程与再生研究室, 济南 250012
    3. 山东大学口腔医学院·口腔医院生物材料研究室, 山东省口腔疾病重点实验室, 口腔生物材料与组织再生山东省工程研究中心, 山东省口腔疾病临床医学研究中心, 济南 250012
    4. 山东大学晶体材料全国重点实验室, 济南 250100
  • 收稿日期:2025-08-06 出版日期:2025-10-18 发布日期:2025-08-13
  • 通讯作者: 葛少华
  • 基金资助:
    国家自然科学基金(82320108004); 国家自然科学基金(81873716); 国家自然科学基金(81670993); 国家自然科学基金(81901010); 国家自然科学基金(81901009); 国家自然科学基金(82471030); 国家自然科学基金(82470981); 国家(海外)优秀青年基金项目; 国家临床重点专科(牙周病学)建设项目; 山东省泰山学者工程项目(tstp20250510)

Establishment and application of key technologies for periodontal tissue regeneration based on microenvironment and stem cell regulation

Baojin MA1,2, Jianhua LI1,3, Yuanhua SANG4, Yang YU1, Jichuan QIU4, Jinlong SHAO1, Kai LI3, Shiyue LIU1, Mi DU1, Lingling SHANG1, Shaohua GE1,*()   

  1. 1. Department of Periodontology, School and Hospital of Stomatology, Shandong University, Jinan 250012, China
    2. Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Shandong University, Jinan 250012, China
    3. Department of Biomaterials, School and Hospital of Stomatology, Shandong University & Shandong Key Laboratory of Oral Diseases & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan 250012, China
    4. State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China
  • Received:2025-08-06 Online:2025-10-18 Published:2025-08-13
  • Contact: Shaohua GE
  • Supported by:
    the National Natural Science Foundation of China(82320108004); the National Natural Science Foundation of China(81873716); the National Natural Science Foundation of China(81670993); the National Natural Science Foundation of China(81901010); the National Natural Science Foundation of China(81901009); the National Natural Science Foundation of China(82471030); the National Natural Science Foundation of China(82470981); Excellent Young Scholars Fund (Overseas) of the National Natural Science Foundation of China; National Clinical Key Specialty (Periodontology) Construction Project; Construction Engineering Special Fund of "Taishan Scholars" of Shandong Province(tstp20250510)

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摘要： 牙周炎在我国患病率高达74.2%，是成人失牙的首位原因，严重影响着口腔健康和全身健康。牙周炎治疗和牙周组织再生是世界关注的难题，山东大学口腔医学院·口腔医院葛少华教授团队围绕“牙周炎症微环境重塑和组织修复再生优化”的关键科学问题，通过阐明牙周炎顽固存在机制、创制生物活性材料调控干细胞再生性能、构建系列引导组织再生膜以促进牙周组织修复，从而创立了牙周炎治疗技术体系，具体研究成果和进展包括：(1)阐明了牙周炎关键致病菌逃避抗菌自噬从而导致炎症损伤的机制，研发了智能抗菌水凝胶和纳米抗菌体系，创制了金属多酚网络微球胶囊，以重塑牙周炎症微环境；(2)解释了材料纳米结构和电活性界面调控干细胞的行为机制，研发了优化纳米结构和电活性生物材料，从而有效提升干细胞再生修复能力；(3)创建系列双相异质屏障膜，完善引导组织再生和原位组织工程技术，激发机体自身修复潜能，促进牙周组织结构再生和功能重建。本课题组研究成果创新了牙周组织再生基础理论，打破了国外产品技术壁垒和专利封锁，建立了牙周再生级联修复策略，提高了我国在牙周组织再生领域的核心竞争力。

关键词: 牙周炎, 微环境, 干细胞, 生物活性材料, 牙周组织再生

Abstract: The prevalence of periodontitis in China is as high as 74.2%, making it the leading cause of tooth loss in adults and severely impacting both oral and overall health. The treatment of periodontitis and periodontal tissue regeneration are global challenges of significant concern. GE Shaohua' s group at School and Hospital of Stomatology, Shandong University has focused on the key scientific issue of "remodeling the periodontal inflammatory microenvironment and optimizing tissue repair and regeneration". They have elucidated the mechanisms underlying the persistence of periodontitis, developed bioactive materials to enhance stem cell regenerative properties, and constructed a series of guided tissue regeneration barrier membranes to promote periodontal tissue repair, leading to the establishment of a comprehensive technology system for the treatment of periodontitis. Specific achievements and progress include: (1) Elucidating the mechanism by which key periodontal pathogens evade antimicrobial autophagy, leading to inflammatory damage; developing intelligent antimicrobial hydrogels and nanosystems, and creating metal-polyphenol network microsphere capsules to reshape the periodontal inflammatory microenvironment; (2) Explaining the mechanisms by which nanomaterial structures and electroactive interfaces regulate stem cell behavior, developing optimized nanostructures and electroactive biomaterials, thereby effectively enhancing the regenerative repair capabilities of stem cells; (3) Creating a series of biphasic heterogeneous barrier membranes, refining guided tissue regeneration and in situ tissue engineering techniques, stimulating the body' s intrinsic repair potential, and synergistically promoting the structural regeneration and functional reconstruction of periodontal tissues. The research outcomes of the group have innovated the fundamental theories of periodontal tissue regeneration, broken through foreign technological barriers and patent blockades, established a cascade repair strategy for periodontal regeneration, and enhanced China' s core competitiveness in the field of periodontal tissue regeneration.

Key words: Periodontitis, Microenvironment, Stem cells, Bioactive materials, Periodontal tissue regeneration

中图分类号: 

  • R781.4
1
GBD 2021 Oral Disorders Collaborators . Trends in the global, regional, and national burden of oral conditions from 1990 to 2021: A systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2025, 405 (10482): 897- 910.

doi: 10.1016/S0140-6736(24)02811-3
2
Huang J , Brumell JH . Bacteria-autophagy interplay: A battle for survival[J]. Nat Rev Microbiol, 2014, 12 (2): 101- 114.

doi: 10.1038/nrmicro3160
3
Liu M , Shao J , Zhao Y , et al. Porphyromonas gingivalis evades immune clearance by regulating lysosome efflux[J]. J Dent Res, 2023, 102 (5): 555- 564.

doi: 10.1177/00220345221146097
4
Liu S , Wang YN , Ma B , et al. Gingipain-responsive thermosensitive hydrogel loaded with SDF-1 facilitates in situ periodontal tissue regeneration[J]. ACS Appl Mater Interfaces, 2021, 13 (31): 36880- 36893.

doi: 10.1021/acsami.1c08855
5
Liu S , Wang YN , Yu L , et al. Development of a thermosensitive hydrogel loaded with DTT and SDF-1 facilitating in situ periodontal bone regeneration[J]. Chem Eng J, 2022, 432, 134308.

doi: 10.1016/j.cej.2021.134308
6
Wang Z, Du J, Leng X, et al. Polyphenol-driven modular self-assembled nano-antibiotic for inflammation control via bacterial infection clearance and pyroptosis inhibition[J/OL]. Adv Funct Mater, 2025, 6(2025-06-23)[2025-07-01]. https://doi.org/10.1002/adfm.202510476.
7
Wang W , Li J , Liu H , et al. Advancing versatile ferroelectric materials toward biomedical applications[J]. Adv Sci, 2021, 8 (1): 2003074.

doi: 10.1002/advs.202003074
8
Liu X , Shen L , Xu W , et al. Low frequency hydromechanics-driven generation of superoxide radicals via optimized piezotronic effect for water disinfection[J]. Nano Energy, 2021, 88, 106290.

doi: 10.1016/j.nanoen.2021.106290
9
Li K , Xu W , Chen Y , et al. Piezoelectric nanostructured surface for ultrasound-driven immunoregulation to rescue titanium implant infection[J]. Adv Funct Mater, 2023, 33 (28): 2214522.

doi: 10.1002/adfm.202214522
10
Liu X , Xu W , Feng J , et al. Adoptive cell transfer of piezo-activated macrophage rescues immunosuppressed rodents from lifethreating bacterial infections[J]. Nat Commun, 2025, 16 (1): 1363.

doi: 10.1038/s41467-025-56460-2
11
Xu W , Yu Y , Li K , et al. Surface-confined piezocatalysis inspired by ROS generation of mitochondria respiratory chain for ultrasound-driven noninvasive elimination of implant infection[J]. ACS Nano, 2023, 17 (10): 9415- 9428.

doi: 10.1021/acsnano.3c01480
12
Liu X, Liang Y, Li Z, et al. Nano-toothbrush for noninvasive control of periodontitis[J/OL]. J Dent Res, 2025, 6(2025-06-26)[2025-07-06]. https://pubmed.ncbi.nlm.nih.gov/40574415.
13
Xie C , Zhang Q , Bianco A , et al. H2S-scavenging hydrogel alleviating mitochondria damage to control periodontitis[J]. J Dent Res, 2025, 104 (2): 172- 182.

doi: 10.1177/00220345241291540
14
Zhang K , Mao X , Zhao H , et al. Selenium-doped carbon dots inhibit ferroptosis by multi-hierarchy iron chelation and mitochondrial homeostasis regulation to control inflammation[J]. Chem Eng J, 2024, 499, 156544.

doi: 10.1016/j.cej.2024.156544
15
Shang L , Yan Y , Li Z , et al. Hydro-sensitive, in situ ultrafast physical self-gelatinizing, and red blood cells strengthened hemostatic adhesive powder with antibiosis and immunoregulation for wound repair[J]. Adv Sci (Weinh), 2024, 11 (4): e2306528.

doi: 10.1002/advs.202306528
16
Chen Y , Yang X , Li K , et al. Phenolic ligand-metal charge transfer induced copper nanozyme with reactive oxygen species-scavenging ability for chronic wound healing[J]. ACS Nano, 2024, 18 (9): 7024- 7036.

doi: 10.1021/acsnano.3c10376
17
Liu J , Shi Y , Zhao Y , et al. A multifunctional metal-phenolic nanocoating on bone implants for enhanced osseointegration via early immunomodulation[J]. Adv Sci (Weinh), 2024, 11 (18): e2307269.

doi: 10.1002/advs.202307269
18
Wang Y , Li Z , Yu R , et al. Metal-phenolic network biointerface-mediated cell regulation for bone tissue regeneration[J]. Mater Today Bio, 2024, 30, 101400.
19
Yang X , Shao J , Zhang Y , et al. Microenvironment-driven Fenton nanoreactor enabled by metal-phenolic encapsulation of calcium peroxide for effective control of dental caries[J]. Adv Healthc Mater, 2024, 13 (10): e2303466.

doi: 10.1002/adhm.202303466
20
Li L , Gao F , Zhang H , et al. A protective growth factor delivery strategy based on polyphenol-protein self-assembly to promote inflammatory bone regeneration[J]. Biomaterials, 2025, 320, 123272.

doi: 10.1016/j.biomaterials.2025.123272
21
Liu Z , Yu Y , Kang W , et al. Self-assembled terbium-amino acid nanoparticles as a model for terbium biosafety and bone repair abi-lity assessment[J]. Compos Part B Eng, 2022, 244, 110186.

doi: 10.1016/j.compositesb.2022.110186
22
Hao M , Zhang Z , Liu C , et al. Hydroxyapatite nanorods function as safe and effective growth factors regulating neural differentiation and neuron development[J]. Adv Mater, 2021, 33 (33): 2100895.

doi: 10.1002/adma.202100895
23
Yu S , Du J , Zhang Q , et al. Mitochondria-targeted polyphenol-cysteine nanoparticles regulating AMPK-mediated mitochondrial homeostasis for enhanced bone regeneration[J]. Adv Funct Mater, 2024, 34 (41): 2402463.

doi: 10.1002/adfm.202402463
24
Hao M , Zhang D , Wang W , et al. HAp thermosensitive nanohydrogel cavities act as brood pouches to incubate and control-release NSCs for rapid spinal cord injury therapy[J]. Adv Funct Mater, 2022, 32 (31): 2203492.

doi: 10.1002/adfm.202203492
25
Li X , Ma B , Li J , et al. A method to visually observe the degradation-diffusion-reconstruction behavior of hydroxyapatite in the bone repair process[J]. Acta Biomater, 2020, 101, 554- 564.

doi: 10.1016/j.actbio.2019.10.044
26
Han J , Li Z , Du J , et al. Natural collagen scaffold with intrinsic piezoelectricity for enhanced bone regeneration[J]. Mater Today Bio, 2025, 31, 101532.

doi: 10.1016/j.mtbio.2025.101532
27
Zhang Y , Wang X , Wang W , et al. Unlocking piezoelectric potential in collagen: Intrafibrillar mineralization matters[J]. ACS Nano, 2025, 19 (29): 26411- 26424.

doi: 10.1021/acsnano.5c02641
28
Wang W , Li K , Ma W , et al. Ultrasound-activated piezoelectric nanostickers for neural stem cell therapy of traumatic brain injury[J]. Nat Mater, 2025, 24 (7): 1137- 1150.

doi: 10.1038/s41563-025-02214-w
29
Wang L , Du J , Liu Q , et al. Wrapping stem cells with wireless electrical nanopatches for traumatic brain injury therapy[J]. Nat Commun, 2024, 15 (1): 7223.

doi: 10.1038/s41467-024-51098-y
30
Ma B , Han J , Zhang S , et al. Hydroxyapatite nanobelt/polylactic acid Janus membrane with osteoinduction/barrier dual functions for precise bone defect repair[J]. Acta Biomater, 2018, 71, 108- 117.

doi: 10.1016/j.actbio.2018.02.033
31
Li X , Wei L , Li J , et al. Multifunctional SDF-1-loaded hydroxyapatite/polylactic acid membranes promote cell recruitment, immunomodulation, angiogenesis, and osteogenesis for biomimetic bone regeneration[J]. Appl Mater Today, 2021, 22, 100942.

doi: 10.1016/j.apmt.2021.100942
32
Liu S , Yang H , Zhang L , et al. Multifunctional barrier membranes promote bone regeneration by scavenging H2O2, generating O2, eliminating inflammation, and regulating immune response[J]. Colloids Surf B Biointerfaces, 2023, 222, 113147.

doi: 10.1016/j.colsurfb.2023.113147
33
Zhang Y , Chen Y , Ding T , et al. Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration[J]. NPJ Regen Med, 2023, 8 (1): 28.

doi: 10.1038/s41536-023-00305-3
34
Zhang L , Li Z , Fu Y , et al. Phased ions-release bilayer-guided bone regeneration membrane with nanostructure-mediated antibacterial adhesion[J]. Small Struct, 2025, 6 (2): 2400408.

doi: 10.1002/sstr.202400408
35
Ding T , Kang W , Li J , et al. An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration[J]. J Nanobiotechnology, 2021, 19 (1): 247.

doi: 10.1186/s12951-021-00992-4
36
Ding T , Li J , Zhang X , et al. Super-assembled core/shell fibrous frameworks with dual growth factors for in situ cementum-ligament-bone complex regeneration[J]. Biomater Sci, 2020, 8 (9): 2459- 2471.

doi: 10.1039/D0BM00102C
37
Shang L , Liu Z , Ma B , et al. Dimethyloxallyl glycine/nanosilicates-loaded osteogenic/angiogenic difunctional fibrous structure for functional periodontal tissue regeneration[J]. Bioact Mater, 2020, 6 (4): 1175- 1188.
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ISSN 1671-167X
CN 11-4691/R
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