journal article·2026-01-15Open access

An Exploration of Nanobiotechnology Bridging Patho-Therapeutics with Regenerative and Clinical Perspectives in Periodontitis

Baozhu Zhang, Muhammad Umar Javed, Yinghe Zhang, Bing Guo

Abstract

Periodontal disease represents a major global concern characterized by chronic biofilm-driven inflammation, excessive oxidative stress, progressive tissue destruction, and impaired regenerative capacity. Beyond conventional antimicrobial approaches, recent progress has shifted toward host-directed and regenerative therapeutic strategies aimed at restoring both oral function and tissue homeostasis. This review consolidates current developments in nanobiotechnology-based materials that modulate immune responses, scavenge reactive oxygen species, and promote angiogenesis and osteogenesis, thereby facilitating the effective regeneration of dental and periodontal tissues. Emphasis is placed on bioresponsive hydrogels, bioactive scaffolds, and gas-releasing platforms that integrate therapeutic regulation with tissue repair. The discussion further highlights key advances in polymeric and inorganic biomaterials designed to balance antibacterial action with cellular compatibility and regenerative potential. By linking pathophysiological mechanisms with material-guided healing processes, this review provides a comprehensive perspective on emerging nanobiotechnological solutions that bridge patho-therapeutics with regenerative and clinical dentistry.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Oral microbiology and periodontitis research · Graphene and Nanomaterials Applications · Periodontal Regeneration and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Radiation Oncology, The People’s Hospital of Baoan, The Second Affiliated Hospital of Shenzhen University, Shenzhen 518101, China

School of Science, Harbin Institute of Technology, Shenzhen 518055, China

Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen 518055, China

Funding

High-quality Development Research Project of Public Hospitals under Bao'an District, Health Bureau of Bao'an District, Shenzhen · Medical and Health Research Project of Bao'an District, Science and Technology Innovation Bureau of Bao'an District, Shenzhen · Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application

References (100+)

Show source-provided references
1. Öçbe, M., Çelebi, E., and Öçbe, Ç.B. (2025). An Overlooked Connection: Oral Health Status in Patients with Chronic Diseases. BMC Oral Health, 25.10.1186/s12903-025-05673-4 ↗
2. Zhu, M., Hao, C., Zou, T., Jiang, S., and Wu, B. (2025). Phage Therapy as an Alternative Strategy for Oral Bacterial Infections: A Systematic Review. BMC Oral Health, 25.10.1186/s12903-024-05399-9 ↗
3. Structure Protects Function: A Multilevel Engineered Surface Modification Renders the Surface of Titanium Dental Implants Resistant to Bacterial Colonization10.1021/acsami.4c21111 ↗
4. Navigating the Dual Burden of Dental and Periodontal Care in Individuals Who Also Smoke: An Expert Review10.1016/j.jdent.2025.105744 ↗
5. Advanced Biomaterials for Targeting Mature Biofilms in Periodontitis Therapy
6. Recent Findings on Metabolomics and the Microbiome of Oral Bacteria Involved in Dental Caries and Periodontal Disease10.1007/s11274-024-04224-3 ↗
7. Are Periodontitis and Dental Caries Associated? A Systematic Review with Meta-analyses10.1111/jcpe.13910 ↗
8. Stangvaltaite-Mouhat, L., Skudutyte-Rysstad, R., Ko, H., Stankeviciene, I., Aleksejuniene, J., and Puriene, A. (2024). Co-Occurrence of Dental Caries and Periodontitis: Multilevel Modelling Approach. BMC Oral Health, 24.10.1186/s12903-024-03918-2 ↗
9. Conventional Diagnostic Criteria for Periodontal Diseases (Plaque-Induced Gingivitis and Periodontitis)10.1111/prd.12579 ↗
10. Transcriptomics Analysis Reveals the Effect of Pulsatilla Decoction Butanol Extract on Endoplasmic Reticulum and Peroxisome Function of Candida albicans in Hyphal State10.1016/j.jep.2024.118826 ↗
11. Gingipain Regulates Isoform Switches of PD-L1 in Macrophages Infected with Porphyromonas Gingivalis10.1038/s41598-025-94954-7 ↗
12. Streptococcus Mutans Biofilms in the Establishment of Dental Caries: A Review10.1007/s13205-025-04227-3 ↗
13. Uniqueness of Candida Auris Cell Wall in Morphogenesis, Virulence, Resistance, and Immune Evasion10.1016/j.micres.2024.127797 ↗
14. Leptin Hormone and Its Effectiveness in Reproduction, Metabolism, Immunity, Diabetes, Hopes and Ambitions10.25122/jml-2021-0153 ↗
15. EBD Spotlight: Antibiotic Resistance in Secondary Endodontic Infections10.1038/s41407-025-2853-x ↗
16. Pattern of Antibiotic Prescription in the Management of Oral Diseases among Dentists in Kuwait10.1016/j.jdent.2004.04.001 ↗
17. An Outcome Audit of the Treatment of Acute Dentoalveolar Infection: Impact of Penicillin Resistance10.1038/sj.bdj.4812415 ↗
18. Necrotising Fasciitis of the Submandibular Region; a Complication of Odontogenic Origin10.1038/bdj.2007.425 ↗
19. The Role of Phenoxymethylpenicillin, Amoxicillin, Metronidazole and Clindamycin in the Management of Acute Dentoalveolar Abscesses—A Review10.1038/sj.bdj.2009.257 ↗
20. Antimicrobial Management of Dental Infections: Updated Review10.1097/MD.0000000000038630 ↗
21. Darvish, S., Budala, D.-G., and Goriuc, A. (2024). Antibacterial Properties of an Experimental Dental Resin Loaded with Gold Nanoshells for Photothermal Therapy Applications. J. Funct. Biomater., 15.10.3390/jfb15040100 ↗
22. Rubilar-Huenchuman, M., Ortega-Villanueva, C., González, I.A., and Palavecino, C.E. (2024). The Effect of Photodynamic Therapy on Enterococcus Spp. and Its Application in Dentistry: A Scoping Review. Pharmaceutics, 16.10.3390/pharmaceutics16060825 ↗
23. NIR-II Triggered Cu(I) Phosphide for Chemodynamic and Photothermal Periodontitis Treatment: Efficient Reduction of Bacterial Co-Aggregation10.1016/j.actbio.2024.08.013 ↗
24. Application of Antimicrobial Sonodynamic Therapy as a Potential Treatment Modality in Dentistry: A Literature Review10.1016/j.jds.2023.11.006 ↗
25. Biomaterials Science and Surface Engineering Strategies for Dental Peri-Implantitis Management
26. Nanoparticle-Mediated Photothermal and Photodynamic Antibacterial Therapy for the Treatment of Periodontitis10.1016/j.colsurfa.2024.135988 ↗
27. Nanomaterials in Antibacterial Photodynamic Therapy and Antibacterial Sonodynamic Therapy10.1002/adfm.202402588 ↗
28. Role of Microbiota in Pain: From Bench to Bedside10.1002/imo2.58 ↗
29. Aherne, O., Ortiz, R., Fazli, M.M., and Davies, J.R. (2022). Effects of Stabilized Hypochlorous Acid on Oral Biofilm Bacteria. BMC Oral Health, 22.10.1186/s12903-022-02453-2 ↗
30. The Application of Phenylboronic Acid Pinacol Ester Functionalized ROS-Responsive Multifunctional Nanoparticles in the Treatment of Periodontitis10.1186/s12951-024-02461-0 ↗
31. Nanotherapies Based on ROS Regulation in Oral Diseases10.1002/advs.202409087 ↗
32. Unveiling the Potential of Sulfur-Containing Gas Signaling Molecules in Acute Lung Injury: A Promising Therapeutic Avenue10.3390/cimb46070426 ↗
33. Munteanu, C., Turnea, M.A., and Rotariu, M. (2023). Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis—A Comprehensive One-Year Review. Antioxidants, 12.10.3390/antiox12091737 ↗
34. Toledano, M., Toledano-Osorio, M., Carrasco-Carmona, Á., Vallecillo, C., Toledano, R., Medina-Castillo, A.L., and Osorio, R. (2020). State of the Art on Biomaterials for Soft Tissue Augmentation in the Oral Cavity. Part II: Synthetic Polymers-Based Biomaterials. Polymers, 12.10.3390/polym12081845 ↗
35. Antibacterial MXenes: An Emerging Non-Antibiotic Paradigm for Surface Engineering of Orthopedic and Dental Implants
36. Calcium-Capturing Hydrogel with Self-Reinforced Multi-Dynamic Networks for Effective Periodontal Bone Regeneration in Three-Dimension10.1002/adfm.202415185 ↗
37. Smart Biomaterials in Dentistry: A Review on the Role of Cellulose and Other Biological Macromolecules in Infection Control10.1016/j.ijbiomac.2025.147293 ↗
38. Biomaterials for Dental Composite Applications: A Comprehensive Review of Physical, Chemical, Mechanical, Thermal, Tribological, and Biological Properties10.1002/pat.5648 ↗
39. Strategies toward Development of Antimicrobial Biomaterials for Dental Healthcare Applications10.1002/bit.27948 ↗
40. Recent Advances of Functional Modules for Tooth Regeneration10.1039/D4TB01027B ↗
41. Iwasaki, M., Takedachi, M., Sawada, K., Miki, K., and Murakami, S. (Clin. Adv. Periodontics, 2025). Preservation Therapy for Vertically Fractured Teeth with Periodontal Tissue Regeneration Using FGF-2, Clin. Adv. Periodontics, Epub ahead of printing.10.1002/cap.10357 ↗
42. Cell Membrane-Coated Nanomicrospheres Mimicking Stem Cell Functions Enhance Angiogenesis for Dental Pulp Regeneration10.1039/D5QM00098J ↗
43. Umapathy, V.R., Natarajan, P.M., and Swamikannu, B. (2025). Regenerative Strategies in Dentistry: Harnessing Stem Cells, Biomaterials and Bioactive Materials for Tissue Repair. Biomolecules, 15.10.3390/biom15040546 ↗
44. Biomimetic Approaches in Prosthodontics: Toward Natural Tooth Restoration and Regeneration10.4103/jpbs.jpbs_1797_24 ↗
45. Mangal, U., Kwon, J.-S., and Choi, S.-H. (2020). Bio-Interactive Zwitterionic Dental Biomaterials for Improving Biofilm Resistance: Characteristics and Applications. Int. J. Mol. Sci., 21.10.3390/ijms21239087 ↗
46. Shi, Y., Sun, X., Fang, J., Li, C., Dong, B., Qi, M., and Wang, L. (2025). Multifunctional Nanomaterials for Dental Photo-Theranostics. Chem. Soc. Rev., Epub ahead of printing.10.1039/D5CS00825E ↗
47. Review of Antimicrobial Nanocoatings in Medicine and Dentistry: Mechanisms of Action, Biocompatibility Performance, Safety, and Benefits Compared to Antibiotics10.1021/acsnano.2c12488 ↗
48. Reise, M., Kranz, S., Heyder, M., Beck, J., Roth, C., Guellmar, A., von Eggeling, F., Schubert, U., Löffler, B., and Sigusch, B. (2023). Salivary Pellicle Formed on Dental Composites Evaluated by Mass Spectrometry—An In Situ Study. Molecules, 28.10.3390/molecules28196804 ↗
49. Exploring the Impact of Biotic and Abiotic Surfaces on Protein Binding Modulation and Bacteria Attachment: Integrating Biological and Mathematical Approaches10.1021/acsnano.5c06573 ↗
50. Enax, J., Ganss, B., Amaechi, B.T., Schulze zur Wiesche, E., and Meyer, F. (2023). The Composition of the Dental Pellicle: An Updated Literature Review. Front. Oral Health, 4.10.3389/froh.2023.1260442 ↗
51. The Transformative Role of Artificial Intelligence in Dentistry: A Comprehensive Overview. Part 1: Fundamentals of AI, and Its Contemporary Applications in Dentistry10.1016/j.identj.2025.02.005 ↗
52. The Transformative Role of Artificial Intelligence in Dentistry: A Comprehensive Overview Part 2: The Promise and Perils, and the International Dental Federation Communique10.1016/j.identj.2025.02.006 ↗
53. Exploring a Decade of Deep Learning in Dentistry: A Comprehensive Mapping Review10.1007/s00784-025-06216-5 ↗
54. Najeeb, M., and Islam, S. (2025). Artificial Intelligence (AI) in Restorative Dentistry: Current Trends and Future Prospects. BMC Oral Health, 25.10.1186/s12903-025-05989-1 ↗
55. Alauddin, M.S., Baharuddin, A.S., and Mohd Ghazali, M.I. (2021). The Modern and Digital Transformation of Oral Health Care: A Mini Review. Healthcare, 9.10.3390/healthcare9020118 ↗
56. The Oral Microbiome: Role of Key Organisms and Complex Networks in Oral Health and Disease10.1111/prd.12393 ↗
57. Risk Factors for Periodontitis & Peri-implantitis10.1111/prd.12447 ↗
58. Recent Advances in Metal Nanoparticles to Treat Periodontitis10.1186/s12951-023-02042-7 ↗
59. DIGITAL DENTISTRY AND ITS IMPACT ON ORAL HEALTH-RELATED QUALITY OF LIFE10.1016/j.jebdp.2023.101946 ↗
60. Acquisition and Establishment of the Oral Microbiota10.1111/prd.12366 ↗
61. Chen, X., Daliri, E.B.-M., Tyagi, A., and Oh, D.-H. (2021). Cariogenic Biofilm: Pathology-Related Phenotypes and Targeted Therapy. Microorganisms, 9.10.3390/microorganisms9061311 ↗
62. The Root of the Matter: Linking Oral Health to Chronic Diseases Prevention
63. Periodontitis and Cardiovascular Diseases: Consensus Report10.1111/jcpe.13189 ↗
64. Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?10.1161/CIR.0b013e31825719f3 ↗
65. Peikert, S.A., Liedtke, N.B., Vach, K., Streletz, E., Rieger, S., Palm, J., Mittelhamm, F., Kirchner, S., Hakes, P., and Gantert, L. (2024). Nutrition and Periodontitis: A Cross-Sectional Study from a Practice-Based Research Network. Nutrients, 16.10.3390/nu16183102 ↗
66. Burden and Impact of Periodontal Diseases on Oral Health-Related Quality of Life and Systemic Diseases and Conditions: Latin America and the Caribbean Consensus 202410.1590/1807-3107bor-2024.vol38.0117 ↗
67. The Oral–Gut Microbiome Axis in Health and Disease10.1038/s41579-024-01075-5 ↗
68. Microbial Ecosystem in the Oral Cavity: Metabolic Diversity in an Ecological Niche and Its Relationship with Oral Diseases10.1016/j.ics.2005.06.071 ↗
69. Periodontal Microorganisms and Alzheimer Disease—A Causative Relationship?10.1111/prd.12429 ↗
70. Interactions between Systemic Diseases and Oral Microbiota Shifts in the Aging Community: A Narrative Review10.1002/jobm.202300141 ↗
71. The Dental Plaque Biofilm Matrix10.1111/prd.12361 ↗
72. Hernández, P., Sánchez, M.C., Llama-Palacios, A., Ciudad, M.J., and Collado, L. (2022). Strategies to Combat Caries by Maintaining the Integrity of Biofilm and Homeostasis during the Rapid Phase of Supragingival Plaque Formation. Antibiotics, 11.10.3390/antibiotics11070880 ↗
73. Bertolini, M., Costa, R.C., Barão, V.A.R., Villar, C.C., Retamal-Valdes, B., Feres, M., and Silva Souza, J.G. (2022). Oral Microorganisms and Biofilms: New Insights to Defeat the Main Etiologic Factor of Oral Diseases. Microorganisms, 10.10.3390/microorganisms10122413 ↗
74. Identification of Protein Components in in Vivo Human Acquired Enamel Pellicle Using LC−ESI−MS/MS10.1021/pr060580k ↗
75. Is the Proteomic Composition of the Salivary Pellicle Dependent on the Substrate Material?10.1002/prca.202100109 ↗
76. Acquired Salivary Pellicle and Oral Diseases: A Literature Review10.1016/j.jds.2020.10.007 ↗
77. Pellicle and Early Dental Plaque in Periodontitis Patients before and after Surgical Pocket Elimination10.3109/00016357.2011.645061 ↗
78. Murray, P.E., Coffman, J.A., and Garcia-Godoy, F. (2024). Oral Pathogens’ Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer’s, Diabetes, and Other Systemic Diseases: A Public Health Crisis—A Comprehensive Review. Pathogens, 13.10.3390/pathogens13121084 ↗
79. The Oral Microbiome in Autoimmune Diseases: Friend or Foe?10.1186/s12967-023-03995-x ↗
80. Li, X., Liu, Y., Yang, X., Li, C., and Song, Z. (2022). The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions. Front. Microbiol., 13.10.3389/fmicb.2022.895537 ↗
81. Advances of Metal-Based Nanomaterials in the Prevention and Treatment of Oral Infections10.1002/adhm.202500416 ↗
82. Rajasekaran, J.J., Krishnamurthy, H.K., Bosco, J., Jayaraman, V., Krishna, K., Wang, T., and Bei, K. (2024). Oral Microbiome: A Review of Its Impact on Oral and Systemic Health. Microorganisms, 12.10.20944/preprints202406.1923.v1 ↗
83. Exploring the Oral-Gut Linkage: Interrelationship between Oral and Systemic Diseases10.1016/j.mucimm.2023.11.006 ↗
84. Al-Qadami, G., Van Sebille, Y., Bowen, J., and Wardill, H. (2022). Oral-Gut Microbiome Axis in the Pathogenesis of Cancer Treatment-Induced Oral Mucositis. Front. Oral Health, 3.10.3389/froh.2022.881949 ↗
85. Suárez, L.J., Arboleda, S., Angelov, N., and Arce, R.M. (2021). Oral Versus Gastrointestinal Mucosal Immune Niches in Homeostasis and Allostasis. Front. Immunol., 12.10.3389/fimmu.2021.705206 ↗
86. Immune System of Dental Pulp in Inflamed and Normal Tissue10.1089/dna.2024.0044 ↗
87. Pohl, S., Akamp, T., Smeda, M., Uderhardt, S., Besold, D., Krastl, G., Galler, K.M., Buchalla, W., and Widbiller, M. (2024). Understanding Dental Pulp Inflammation: From Signaling to Structure. Front. Immunol., 15.10.3389/fimmu.2024.1474466 ↗
88. The immune landscape in apical periodontitis: From mechanism to therapy10.1111/iej.14125 ↗
89. Barbero-Navarro, I., Irigoyen-Camacho, M.E., Zepeda-Zepeda, M.A., Ribas-Perez, D., Castaño-Seiquer, A., and Sofian-Pauliuc, I. (2024). Understanding the Dynamics of Inflammatory Cytokines in Endodontic Diagnosis: A Systematic Review. Diagnostics, 14.10.3390/diagnostics14111099 ↗
90. Li, Q. (2025). Diagnostic Utility of Th2 Cytokines (IL-4, IL-5, IL-10, and IL-13) in Pulpal Blood for Assessing Pulpitis Severity. BMC Oral Health, 25.10.1186/s12903-025-05936-0 ↗
91. EZH2 knockout in mice activates STAT3 signalling via STAT3 methylation and modulates ferroptosis in pulpitis-affected dental pulp vascular endothelial cells: A laboratory investigation10.1111/iej.14232 ↗
92. Role of Molybdenum in Material Immunomodulation and Periodontal Wound Healing: Targeting Immunometabolism and Mitochondrial Function for Macrophage Modulation10.1016/j.biomaterials.2022.121439 ↗
93. Liu, C., Mo, L., Niu, Y., Li, X., Zhou, X., and Xu, X. (2017). The Role of Reactive Oxygen Species and Autophagy in Periodontitis and Their Potential Linkage. Front. Physiol., 8.10.3389/fphys.2017.00439 ↗
94. The Impact of Antioxidant Agents Complimentary to Periodontal Therapy on Oxidative Stress and Periodontal Outcomes: A Systematic Review10.1016/j.archoralbio.2015.05.007 ↗
95. Sui, L., Wang, J., Xiao, Z., Yang, Y., Yang, Z., and Ai, K. (2020). ROS-Scavenging Nanomaterials to Treat Periodontitis. Front. Chem., 8.10.3389/fchem.2020.595530 ↗
96. Multifunctional Metal–Phenolic Composites Promote Efficient Periodontitis Treatment via Antibacterial and Osteogenic Properties10.1021/acsami.3c19621 ↗
97. Pt-Clusters-Equipped Antioxidase-Like Biocatalysts as Efficient ROS Scavengers for Treating Periodontitis10.1002/smll.202306966 ↗
98. Melatonin-Derived Carbon Dots with Free Radical Scavenging Property for Effective Periodontitis Treatment via the Nrf2/HO-1 Pathway10.1021/acsnano.3c12580 ↗
99. Regulation of Macrophage Polarization Through Periodic Photo-Thermal Treatment to Facilitate Osteogenesis10.1002/smll.202202691 ↗
100. Remodeling the Periodontitis Microenvironment for Osteogenesis by Using a Reactive Oxygen Species-Cleavable Nanoplatform10.1016/j.actbio.2021.08.009 ↗