Mitochondria-regulating biomaterials for periodontitis therapy: From dysfunction mechanisms to tissue regeneration

Yan Xuan; Hu Xiaojing; Wei Junchao

doi:10.70401/bmeh.2026.0039

Mitochondria-regulating biomaterials for periodontitis therapy: From dysfunction mechanisms to tissue regeneration

Xuan Yan

1,2,3

Xiaojing Hu

1,3,*

Junchao Wei

1,2,3,*

Affiliation +

*Correspondence to: Junchao Wei, School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China. E-mail: weijunchao@ncu.edu.cn
Xiaojing Hu, School of Stomatology, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi, China; Jiangxi Province Clinical Research Center for Oral Disease, Nanchang 330006, Jiangxi, China. E-mail: DentistHXJ@163.com

BME Horiz. 2027;5:202631. 10.70401/bmeh.2026.0039

Received: July 18, 2026Accepted: October 23, 2026Published: October 27, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Periodontitis, a bacteria-induced chronic inflammatory disease, is characterized by progressive destruction of periodontal tissues, thereby severely affecting aesthetics, mastication, and quality of life. A critical mechanism of periodontitis is mitochondrial dysfunction, therefore, various mitochondria-regulating biomaterials have been designed to restore mitochondrial homeostasis, and further enhance antibacterial defense, modulate immune responses, and promote osteogenesis and angiogenesis. In this review, the pathogenic mechanisms derived from mitochondrial dysfunction of various cell types and their effect on the periodontal regeneration are comprehensively summarized. Furthermore, mitochondria-regulating biomaterials for periodontitis treatment along with the challenges and future perspectives for clinical translation are discussed.

Keywords

Mitochondria-regulating biomaterials, mitochondrial dysfunction, periodontitis, periodontal tissue regeneration

References

1. Yu X, Liu H, Chen L, Cheng X, Wu G, Forouzanfar T, et al. Thermosensitive antibacterial nanocomposite hydrogel guiding macrophage polarization and bone regeneration for periodontitis treatment. Bioact Mater. 2026;55:376-390.

[DOI] [PubMed] [PMC]
2. Yao H, Turali Emre ES, Fan Y, Wang J, Liu F, Wei J. L-arginine modified mesoporous bioactive glass with ROS scavenging and NO release for periodontitis treatment. Bioact Mater. 2025;48:200-216.

[DOI] [PubMed] [PMC]
3. Wang F, Wang Y, Sheng J, Zhang K, Cao Y, Han X, et al. A dual-functional Janus nanofibrous membrane as an immunomodulatory barrier for periodontitis regeneration under diabetic conditions. Mater Today Bio. 2026;37:102869.

[DOI] [PubMed] [PMC]
4. Zhang S, Zhang X, Huang J, Zhou N, Zhang F, Ren J, et al. Curcumin-alendronate carbon dots: A dual-logic strategy for precision treatment of periodontitis. Mater Today Bio. 2025;33:102073.

[DOI] [PubMed] [PMC]
5. Luo X, He Y, Zeng C, Chen S, Wang L, Luo G, et al. Long-rod nano-hydroxyapatite derived G-LR-HA@TZ acts as a multifunctional regenerative tool for periodontal bone. Bioact Mater. 2026;62:547-568.

[DOI] [PubMed] [PMC]
6. Yang S, Gao F, Zou Y, Lei Y, Liu Z, Wang S, et al. Injectable thermogel-loaded Bi₂S₃ nanorods for synergistic photothermal bacterial elimination and anti-inflammation to remodel periodontitis microenvironment. Small. 2026;22(19):e13986.

[DOI] [PubMed]
7. Tao J, Sun Y, Wang G, Sun J, Dong S, Ding J. Advanced biomaterials for targeting mature biofilms in periodontitis therapy. Bioact Mater. 2025;48:474-492.

[DOI] [PubMed] [PMC]
8. Duan Q, Wang X, Wang S, Yang Z, Tan W, He Z, et al. Wisdom across interfaces: Adhesion mechanism and application potential of wet-adhesive hydrogel in periodontal tissue. Bioact Mater. 2026;56:33-56.

[DOI] [PubMed] [PMC]
9. Li J, Hou M, Wang R, Li M, Chen J, Ge M, et al. Non-antibiotic lipid complex-in-thermogel strikes twice: Multimodal photosensitive antibacterial meets immunomodulation-boosted healing for periodontitis treatment. Mater Today Bio. 2026;37:102781.

[DOI]
10. Ding Q, Teng Y, Zhu H, Jia Z, Xu S, Hu B, et al. Local periodontal injection, systemic heart repair: A dual-functional hydrogel for non-invasive concurrent treatment of periodontitis and myocardial infarction. Bioact Mater. 2026;62:17-33.

[DOI]
11. Gan Z, Xiao Z, Zhang Z, Li Y, Liu C, Chen X, et al. Stiffness-tuned and ROS-sensitive hydrogel incorporating complement C5a receptor antagonist modulates antibacterial activity of macrophages for periodontitis treatment. Bioact Mater. 2023;25:347-359.

[DOI] [PubMed] [PMC]
12. Wang Q, Zhao Y, Han L, Li C, Wang Z, Zhang X, et al. A dual-action nucleoside-based supramolecular hydrogel combats periodontitis by disrupting the bacteria-osteoclast cascade. Adv Mater. 2026;38(24):e16181.

[DOI]
13. Zhou T, Xie Y, Cheng A, Wu J, Yao Y, Yin Y, et al. Nanotherapeutics for microenvironment modulation and immune homeostasis in periodontitis treatment. Biomaterials. 2026;326:123713.

[DOI]
14. Mutailifu D, Aini A, Maimaitiaili A. Integrated bioinformatics analysis and machine learning approach for the identification of immune-related genes in the diagnosis of aortic valve calcification with periodontitis. Biomed Technol. 2025;10:100087.

[DOI]
15. Qin Y, Chen L, Ding Z, Zhang C, Cheng L, Tian W, et al. Covalent organic framework-based artificial antioxidases with π-electron delocalization and asymmetric coordination sites for superior inflammation inhibition and oral bone modulation. Adv Mater. 2026;38(5):e14915.

[DOI]
16. Ou Y, Liu Y, Cai Q, Wan P, Gao G, Li X, et al. A sonosensitizer-cationic polypeptide conjugate potentiates sonodynamic therapy for mature biofilm eradication and periodontitis treatment. Adv Funct Mater. 2026;36(45):e75242.

[DOI]
17. Wu Y, Liao J, Pu Y, Gong L, Liu X, Wu Y, et al. Mechanistic insights and therapeutic applications of metal-based nanomaterials in oral infectious diseases: Current advances and future perspectives. Biomaterials. 2026;324:123528.

[DOI]
18. Han Z, Bao L, Yu Y, Zhao Y, Wang M, Sun Y, et al. Injectable short-fiber hydrogel with fatigue resistance and antibacterial properties for synergistic periodontitis therapy. Chem Eng J. 2025;520:166298.

[DOI]
19. Miao MA, Wu XQ, Yuan Y, Wang YJ, Dai WT. Biochanin A as a potential agent in the disease therapy via mitochondria-mediated mechanisms. Biomed Pharmacother. 2025;190:118363.

[DOI]
20. Deng Y, Xiao J, Ma L, Wang C, Wang X, Huang X, et al. Mitochondrial dysfunction in periodontitis and associated systemic diseases: Implications for pathomechanisms and therapeutic strategies. Int J Mol Sci. 2024;25(2):1024.

[DOI] [PubMed] [PMC]
21. Yan J, Yang T, Ma S, Li D, Hu C, Tan J. Macrophage-derived mitochondria-rich extracellular vesicles aggravate bone loss in periodontitis by disrupting the mitochondrial dynamics of BMSCs. J Nanobiotechnology. 2025;23(1):208.

[DOI] [PubMed] [PMC]
22. Wang Y, Zhang S, Sun J, Zhang Q, Zhang X. A novel antimicrobial peptide AH-12 attenuates mitochondrial response to inflammatory stimuli and prevents periodontitis via antibacterial and anti-inflammatory effects. Biomater Adv. 2026;182:214711.

[DOI] [PubMed]
23. Wang X, Wang C, Ren M, Shi Y, Dong T, Liu Z, et al. From mitochondria to immune networks: New mesenchymal stem cell strategies to treat periodontitis. Stem Cell Res Ther. 2025;16(1):470.

[DOI] [PubMed] [PMC]
24. Liu Q, Cong R, Yu J, Zhang X, Tu J, Dong Y, et al. Ros-sensitive hydrogel system incorporating mitochondria-targeted liposomes for periodontitis treatment. Mater Des. 2025;257:114557.

[DOI]
25. Wiese M, Gerlach RG, Popp I, Matuszak J, Mahapatro M, Castiglione K, et al. Hypoxia-mediated impairment of the mitochondrial respiratory chain inhibits the bactericidal activity of macrophages. Infect Immun. 2012;80(4):1455-1466.

[DOI] [PubMed] [PMC]
26. Dunham-Snary KJ, Surewaard BG, Mewburn JD, Bentley RE, Martin AY, Jones O, et al. Mitochondria in human neutrophils mediate killing of Staphylococcus aureus. Redox Biol. 2022;49:102225.

[DOI] [PubMed] [PMC]
27. Jia Y, Li Z, Huang P, Wang Y, Yang B. Mechanisms and therapeutic perspectives of mitochondrial dysfunction of macrophages in periodontitis. Front Cell Infect Microbiol. 2025;15:1634909.

[DOI] [PubMed] [PMC]
28. Xiang Y, Li Z, He X, Chu X, Gao C, Guo J, et al. Puerarin relives inflammation, bone destruction and facilitates osteogenic differentiation in periodontitis by enhancing mitochondrial autophagy via activating mitochondrial Mitofusin 2. Stem Cell Res Ther. 2025;16(1):218.

[DOI]
29. Wang S, Liu J, Zhou L, Xu H, Zhang D, Zhang X, et al. Research progresses on mitochondrial-targeted biomaterials for bone defect repair. Regen Biomater. 2024;11:rbae082.

[DOI] [PubMed] [PMC]
30. Han M, Tang K, Chen Z. Preparation of NIR responsive resveratrol@Au nanocages using for regulating oxidative stress microenvironment of periodontitis. Chem Eng J. 2025;504:158774.

[DOI]
31. Xiong QW, Jiang K, Shen XW, Ma ZR, Yan XM, Xia H, et al. The requirement of the mitochondrial protein NDUFS8 for angiogenesis. Cell Death Dis. 2024;15(4):253.

[DOI] [PubMed] [PMC]
32. Huan MJ, Fu PP, Chen X, Wang ZX, Ma ZR, Cai SZ, et al. Identification of the central role of RNA polymerase mitochondrial for angiogenesis. Cell Commun Signal. 2024;22(1):343.

[DOI] [PubMed] [PMC]
33. Wadan AS, Moshref AS, Emam AM, Bakry YG, Khalil BO, Chaurasia A, et al. Mitochondrial dysfunction as a key player in aggravating periodontitis among diabetic patients: Review of the current scope of knowledge. Naunyn Schmiedebergs Arch Pharmacol. 2025;398(10):13173-13204.

[DOI]
34. Zhai J, Yang X, Ren S, Wang Y, Chen J, Luo J, et al. Spatiotemporally programmable hydrogel enables NIR-triggered biofilm disruption and mitophagy-driven immunometabolic remodeling for periodontitis. Biomaterials. 2026;334:124281.

[DOI]
35. Jin Y, Du J, Wang Z, Ge S, Ma B. Macrophage-targeted self-assembled nanosystem for periodontitis treatment. J Dent Res. 2026;105(3):353-363.

[DOI] [PubMed]
36. Zhang Y, Shi J, Zhu J, Ding X, Wei J, Jiang X, et al. Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS. Acta Pharm Sin B. 2024;14(11):5026-5036.

[DOI] [PubMed] [PMC]
37. Cheng Z, Huang S, Tang Q, Zhang D, Huang L. Vitamin A family suppresses periodontitis by restoring mitochondrial metabolic reprogramming in macrophages through JAK-STAT pathway. Front Genet. 2025;16:1505933.

[DOI] [PubMed] [PMC]
38. Zhang WJ, Tian BM, Li F, Li X, Wu RX, Yin Y, et al. Bioengineered extracellular vesicles escape lysosomal degradation and deliver Tet-PKM2 for macrophage immunometabolic reprogramming and periodontitis treatment. Bioact Mater. 2026;59:607-628.

[DOI] [PubMed] [PMC]
39. Chen L, Hu P, Hong X, Li B, Ping Y, Chen S, et al. Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy. Int J Oral Sci. 2025;17(1):32.

[DOI] [PubMed] [PMC]
40. Jiang Y, Wang Z, Zhang K, Hu Y, Shang D, Jiang L, et al. Dynamin-related protein 1 orchestrates inflammatory responses in periodontal macrophages via interaction with hexokinase 1. J Clin Periodontol. 2025;52(4):622-636.

[DOI] [PubMed]
41. Wu X, Lu J, Xiong Z, Huang J, Zhang J, Luo L. Melatonin alleviates periodontitis by suppressing neutrophil extracellular traps–dependent neutrophil recruitment. J Clin Periodontol. 2026;53(4):630-643.

[DOI]
42. Chen Y, Mei E, Nan S, Chen X, Zhang P, Zhu Q, et al. Fibrin aggravates periodontitis through inducing NETs formation from mitochondrial DNA. Oral Dis. 2025;31(2):577-588.

[DOI] [PubMed]
43. Wang Z, Saxena A, Yan W, Uriarte SM, Siqueira R, Li X. The impact of aging on neutrophil functions and the contribution to periodontitis. Int J Oral Sci. 2025;17(1):10.

[DOI]
44. Huang J, Li Y, Ye Q, Li R, Wang Y, Wang Q, et al. PGC-1α-mediated mitochondrial homeostasis imbalance aggravated gingival lesions of diabetic periodontitis by disrupting ECM remodeling of human gingival fibroblast. Redox Biol. 2025;86:103829.

[DOI] [PubMed] [PMC]
45. Liu J, Wang X, Xue F, Zheng M, Luan Q. Abnormal mitochondrial structure and function are retained in gingival tissues and human gingival fibroblasts from patients with chronic periodontitis. J Periodontal Res. 2022;57(1):94-103.

[DOI] [PubMed]
46. Bi CS, Wu YK, Li HY, Cheng ZJ, Hussain L, Li XJ. Mitophagy attenuates pyroptosis in human gingival fibroblasts through inhibition of NLRP3 inflammasome activation. Arch Oral Biol. 2025;179:106378.

[DOI] [PubMed]
47. Liu J, Wang Y, Shi Q, Wang X, Zou P, Zheng M, et al. Mitochondrial DNA efflux maintained in gingival fibroblasts of patients with periodontitis through ROS/mPTP pathway. Oxid Med Cell Longev. 2022;2022:1000213.

[DOI] [PubMed] [PMC]
48. Cheng X, Cai Y, Geng Y, Zang X, Liu J, Luan Q. Mitochondrial calcium overload drives mtDNA-cGAS-STING activation via VDAC1 and MCU upregulation in periodontitis. Int J Mol Sci.. 2026;27(10):4317.

[DOI]
49. Shi L, Ji Y, Zhao S, Li H, Jiang Y, Mao J, et al. Crosstalk between reactive oxygen species and Dynamin-related protein 1 in periodontitis. Free Radic Biol Med. 2021;172:19-32.

[DOI]
50. Chen Y, Ji Y, Jin X, Sun X, Zhang X, Chen Y, et al. Mitochondrial abnormalities are involved in periodontal ligament fibroblast apoptosis induced by oxidative stress. Biochem Biophys Res Commun. 2019;509(2):483-490.

[DOI]
51. Weng J, Zhang Z, Zeng L, Xia J, Xu Z, Zhu G, et al. Effect and mechanism of apoptotic bodies from inflammatory periodontal ligament stem cells on macrophage M1 polarisation. Int Dent J. 2026;76(1):103981.

[DOI] [PubMed] [PMC]
52. Cai Q, Quan Z, Yang X, Li C, Chen Y, Wei Y, et al. GATA-1-driven TOMM20-mediated mitophagy regulates PDLSCs osteogenesis and enhances periodontal bone regeneration. Biochem Biophys Res Commun. 2026;795:153121.

[DOI]
53. Li X, Tian BM, Yin Y, Zhou H, Gan D, Liu F, et al. Melatonin ameliorates inflammation-induced mitochondrial dysfunction and cementoblastic differentiation in cells by regulating the METTL3/LINC01444/HSPD1 axis. Fundam Res. 2026;6(3):1948-1965.

[DOI]
54. You J, Wu Q, Tang S, Kang J, Li D, Wang Q, et al. Microenvironment-heterogeneity-driven self-adaptive CuMo diatomic nanozyme hydrogel for NIR-II photoacoustic imaging-assisted periodontitis theranostics. Adv Funct Mater. 2026;36(80):e78028.

[DOI]
55. Usui M, Onizuka S, Sato T, Kokabu S, Ariyoshi W, Nakashima K. Mechanism of alveolar bone destruction in periodontitis - Periodontal bacteria and inflammation. Jpn Dent Sci Rev. 2021;57:201-208.

[DOI] [PubMed] [PMC]
56. Jacho D, Babaniamansour P, Osorio R, Toledano M, Rabino A, Garcia-Mata R, et al. Deciphering the cell-specific effect of osteoblast-macrophage crosstalk in periodontitis. Tissue Eng Part A. 2023;29(21-22):579-593.

[DOI] [PubMed] [PMC]
57. Yu Z, Li Y, Zhang S, Cao R, Liu K, Deng J, et al. A ZIF90-tungsten-based nanoparticle hydrogel system with antibacterial and antioxidant properties promotes periodontal bone regeneration by modulating the ROS/Plagl1/Wnt pathway. Biomaterials. 2026;334:124307.

[DOI] [PubMed]
58. Zhang X, Jiang Y, Mao J, Ren X, Ji Y, Mao Y, et al. Hydroxytyrosol prevents periodontitis-induced bone loss by regulating mitochondrial function and mitogen-activated protein kinase signaling of bone cells. Free Radic Biol Med. 2021;176:298-311.

[DOI] [PubMed]
59. Cheng J, Tao D, Wang W, Wang H, Wang H, Liang Y, et al. CKAP4 regulates ERS-induced apoptosis in osteoclasts through FOXO3 in periodontitis. Cell Prolif. 2026;59(9):e70208.

[DOI] [PubMed] [PMC]
60. Abulaiti G, Qin X, Chen L, Zhu G. Mitophagy and its significance in periodontal disease. Oral Dis. 2025;31(7):2001-2018.

[DOI]
61. Gou H, Wang T, Chen Y, Zhou Y, Li J, Xu Y. Role of Pink1 in regulating osteoclast differentiation during periodontitis. J Dent Res. 2025;104(7):753-762.

[DOI]
62. Jang JS, Hong SJ, Mo S, Kim MK, Kim YG, Lee Y, et al. PINK1 restrains periodontitis-induced bone loss by preventing osteoclast mitophagy impairment. Redox Biol. 2024;69:103023.

[DOI] [PubMed] [PMC]
63. Jiang Y, Chen J, Guo S, Cui W, Zhou Y, Chen X, et al. Role of TRPM2 in oxidative stress-mediated bone loss in periodontitis. J Dent Res. 2025;104(10):1105-1115.

[DOI] [PubMed]
64. Ma Y, Han X, Yan K, Yang Y, Zhang K, Wang Y, et al. M2 macrophage-derived mitochondrial transplantation promotes periodontal bone regeneration by regulating metabolic homeostasis via activating p38-MAPK signaling pathway. Stem Cell Res Ther. 2025;16(1):315.

[DOI] [PubMed] [PMC]
65. Zhou P, Ma X, Hu Y, Chen Y, Wang H, Wang T, et al. Sericin-based dual-module microspheres promote periodontal regeneration through four-dimensional microenvironment remodeling. Biomaterials. 2026;328:123843.

[DOI]
66. Liang Y, Harris FL, Brown LAS. Alcohol induced mitochondrial oxidative stress and alveolar macrophage dysfunction. Biomed Res Int. 2014;2014:371593.

[DOI] [PubMed] [PMC]
67. Silwal P, Kim JK, Kim YJ, Jo EK. Mitochondrial reactive oxygen species: Double-edged weapon in host defense and pathological inflammation during infection. Front Immunol. 2020;11:1649.

[DOI]
68. Wise AD, TenBarge EG, Mendonça JDC, Mennen EC, McDaniel SR, Reber CP, et al. Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps. Cell Host Microbe. 2025;33(3):341-357.e9.

[DOI] [PubMed] [PMC]
69. Fretes A, Lara B, Calo G, Rojas Campión I, Materazzi L, Sabbione F, et al. Porphyromonas gingivalis outer membrane vesicles induce an activated but permissive neutrophil phenotype. Front Immunol. 2026;17:1896511.

[DOI] [PubMed] [PMC]
70. Fleetwood AJ, Lee MKS, Singleton W, Achuthan A, Lee MC, O’Brien-Simpson NM, et al. Metabolic remodeling, inflammasome activation, and pyroptosis in macrophages stimulated by Porphyromonas gingivalis and its outer membrane vesicles. Front Cell Infect Microbiol. 2017;7:351.

[DOI] [PubMed] [PMC]
71. Wu J, Guo Z, Wang L, Shen Y, Li X, Zhang Z, et al. Porphyromonas gingivalis induces Zbp1-mediated macrophages PANoptosis in periodonitis pathophysiology. Exp Mol Med. 2025;57(5):964-978.

[DOI] [PubMed] [PMC]
72. Yang Y, Zeng Y, Liu Z, Huang JA. Pathogen-induced mitochondrial dysfunction: Mechanistic insights, immune crosstalk, and therapeutic opportunities. Front Cell Infect Microbiol. 2025;15:1714998.

[DOI] [PubMed] [PMC]
73. Zhao D, Du B, Xu J, Xie Q, Lu Z, Kang Y. Baicalin promotes antibacterial defenses by modulating mitochondrial function. Biochem Biophys Res Commun. 2022;621:130-136.

[DOI] [PubMed]
74. Ma S, He H, Ren X. Single-cell and transcriptome analysis of periodontitis: Molecular subtypes and biomarkers linked to mitochondrial dysfunction and immunity. J Inflamm Res. 2024;17:11659-11678.

[DOI]
75. Yang K, Zhao Q, Sun Y, Lin L, Han X. Mitochondrial immunometabolism in sepsis: Orchestrating macrophage polarization and dysfunction. Eur J Med Res. 2025;31(1):36.

[DOI] [PubMed] [PMC]
76. Zhang X, Zhang D, Guo J, Shi C, Gong Z. Mitochondrial transfer as a driver of immune microenvironment remodeling. Front Immunol. 2026;17:1743261.

[DOI] [PubMed] [PMC]
77. Gonzalez-Menendez P, Sainz RM, Evelson P. Editorial: Oxidative metabolism in inflammation. Front Immunol. 2024;15:1507700.

[DOI] [PubMed] [PMC]
78. Van den Bossche J, Baardman J, Otto NA, van der Velden S, Neele AE, van den Berg SM, et al. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages. Cell Rep. 2016;17(3):684-696.

[DOI]
79. Mao X, Wang C, Yu S, Zhang K, Wang Z, Du J, et al. Mitochondria-targeted co-assembled nanosystem with multimodal mitochondrial DNA level control to alleviate inflammation and promote chronic wound healing. Biomaterials. 2026;329:123981.

[DOI]
80. Ma S, He H, Ren X, Chen R, Zhao R, Dong K, et al. Luteolin ameliorates periodontitis by modulating mitochondrial dynamics and macrophage polarization via the JAK2/STAT3 pathway. Int Immunopharmacol. 2025;144:113612.

[DOI] [PubMed]
81. Li Y, Li S, Wu J, Li J, Chen H, Jia J, et al. Bioengineered apoptotic vesicles overcome energy crisis in bone regeneration through mitochondrial metabolic activation. Bioact Mater. 2026;56:115-135.

[DOI] [PubMed] [PMC]
82. Huang X, Zheng L, Li P, Lin Z, Huang S, Zhou C. Fabrication of 3D printed trabecular bone-templated scaffolds modified with rare earth europium (III)-based complex for enhancing mitochondrial function in bone regeneration. Appl Mater Today. 2024;37:102130.

[DOI]
83. Qiu Y, Tian J, Lou Y, Yang X, Liu H, Pang C, et al. Calcium silicate induces mitophagy-mediated metabolic shifts toward oxidative phosphorylation in BMSCs to facilitate osteogenesis and bone regeneration. Regen Biomater. 2025;12:rbaf101.

[DOI] [PubMed] [PMC]
84. Suh J, Kim NK, Shim W, Lee SH, Kim HJ, Moon E, et al. Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis. Cell Metab. 2023;35(2):345-360.e7.

[DOI] [PubMed]
85. Nie S, Yu Y, Yan R, Liu T, Du Y, Luo Z, et al. Bone-targeted mitochondrial delivery via magnetic-temperature responsive artificial cells for repairing age-related fractures. Front Pharmacol. 2025;16:1725973.

[DOI] [PubMed] [PMC]
86. Wang L, Huang X, Dai T, Xie J, Lv QX, Hou Y, et al. The role of mitochondrial dynamics in the TiO₂ nanotube-accelerated osteogenic differentiation of MC3T3-E1 cells. Biochem Biophys Res Commun. 2021;535:33-38.

[DOI]
87. Fukai T, Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: Role in ROS signaling and angiogenesis. Cells. 2020;9(8):1849.

[DOI]
88. Reichard A, Asosingh K. The role of mitochondria in angiogenesis. Mol Biol Rep. 2019;46(1):1393-1400.

[DOI] [PubMed] [PMC]
89. Luo Z, Yao J, Wang Z, Xu J. Mitochondria in endothelial cells angiogenesis and function: Current understanding and future perspectives. J Transl Med. 2023;21(1):441.

[DOI]
90. Szewczyk A, Jarmuszkiewicz W, Koziel A, Sobieraj I, Nobik W, Lukasiak A, et al. Mitochondrial mechanisms of endothelial dysfunction. Pharmacol Rep. 2015;67(4):704-710.

[DOI]
91. Pang B, Dong G, Pang T, Sun X, Liu X, Nie Y, et al. Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: Focus on mitochondrial dysfunction. Angiogenesis. 2024;27(4):623-639.

[DOI] [PubMed] [PMC]
92. Cannito S, Giardino I, D’Apolito M, Pettoello-Mantovani M, Scaltrito F, Mangieri D, et al. The multifaceted role of mitochondria in angiogenesis. Int J Mol Sci. 2025;26(16):7960.

[DOI] [PubMed] [PMC]
93. Shen Y, Wang H, Xie H, Zhang J, Ma Q, Wang S, et al. L-arginine promotes angio-osteogenesis to enhance oxidative stress-inhibited bone formation by ameliorating mitophagy. J Orthop Translat. 2024;46:53-64.

[DOI] [PubMed] [PMC]
94. Zhao Y, Xiong R, Jin S, Li Y, Dong T, Wang W, et al. MitoQ alleviates H₂O₂-induced mitochondrial dysfunction in keratinocytes through the Nrf2/PINK1 pathway. Biochem Pharmacol. 2025;234:116811.

[DOI]
95. Mitchell ES, Lemke S, Woodhead B, Coleman D. Oral subchronic toxicity study and genetic toxicity evaluation of mitoquinone mesylate. J Appl Toxicol. 2024;44(10):1555-1571.

[DOI]
96. Li X, Zhao Y, Peng H, Gu D, Liu C, Ren S, et al. Robust intervention for oxidative stress-induced injury in periodontitis via controllably released nanoparticles that regulate the ROS-PINK1-Parkin pathway. Front Bioeng Biotechnol. 2022;10:1081977.

[DOI] [PubMed] [PMC]
97. Xie W, Wang Y, Wu J, Wang X, Wu J, Cheng B, et al. Hierarchically targeting and ROS-responsive platform for diabetic periodontitis treatment through mitochondrial repair in M1 macrophages. ACS Appl Mater Interfaces. 2026;18(1):566-587.

[DOI] [PubMed]
98. Wieland JG, Naskar N, Reess K, dos Santos DNS, Weise JM, Blatt T, et al. Impact of coenzyme Q₁₀ on mitochondrial metabolism: A complementary study using fluorescence lifetime imaging and electron microscopy. Front Biosci. 2024;29(11):383.

[DOI]
99. Huang N, Cao L, Xu Y, Pan L, Zheng A, Wang X, et al. A mitochondria-targeted nanoantioxidant restores alveolar bone homeostasis in periodontitis by quenching ROS and suppressing the cGAS-STING pathway. Bioact Mater. 2026;60:574-589.

[DOI] [PubMed] [PMC]
100. Zheng Y, Mao L, Wang Q, Hu H, Xarpidin B, Luo Z, et al. Mitochondria-targeted ROS scavenging natural enzyme cascade nanogels for periodontitis treatment via hypoxia alleviation and immunomodulation. Adv Sci. 2025;12(29):e07481.

[DOI] [PubMed] [PMC]
101. Deng Y, Jiang X, Che Z, Shang Y, Hu M, Wang W, et al. Fisetin carbon dots alleviate periodontitis by enhancing mitophagy through regulation of sirtuin 3 SUMOylation. J Nanobiotechnology. 2025;23(1):767.

[DOI] [PubMed] [PMC]
102. Xin X, Liu J, Liu X, Xin Y, Hou Y, Xiang X, et al. Melatonin-derived carbon dots with free radical scavenging property for effective periodontitis treatment via the Nrf2/HO-1 pathway. ACS Nano. 2024;18(11):8307-8324.

[DOI] [PubMed]
103. Yang Y, Zhu Y, Yuan H, Yang Z, Zhou J. Asiatic acid-loaded hydrogel ameliorates diabetic periodontitis via mitophagy-mediated M2 macrophage polarization. ACS Omega. 2026;11(7):12229-12241.

[DOI] [PubMed] [PMC]
104. He XT, Li X, Zhang M, Tian BM, Sun LJ, Bi CS, et al. Role of molybdenum in material immunomodulation and periodontal wound healing: Targeting immunometabolism and mitochondrial function for macrophage modulation. Biomaterials. 2022;283:121439.

[DOI] [PubMed]
105. Shan Y, Zhong J, Sun Q, Gao W, Zhang C, Chen H, et al. Dual nanozymes-loaded core-shell microneedle patches with antibacterial and NETs-degradation bifunctional properties for periodontitis treatment. Bioact Mater. 2025;53:161-177.

[DOI] [PubMed] [PMC]
106. Hu Z, Chen G, Long Z. Research progress on mitochondria in bone defect repair: Mechanisms and therapeutic implications. Front Bioeng Biotechnol. 2026;14:1763027.

[DOI] [PubMed] [PMC]
107. Yao Y, Lei X, Li X, Ge Y, Wang Y, Qin X, et al. A trackable mitochondria-targeting nanosystem for mitochondrial redox and mitophagy regulation in diabetic retinopathy management. Chem Eng J. 2025;505:159618.

[DOI]
108. Tan YJ, Li X, Zhang WJ, Cao YM, Zou JK, Jing L, et al. Mitochondria-targeted delivery of zinc-coordinated resveratrol nanoparticles rescues the osteogenic potential of periodontal ligament stem cells compromised by inflammation for periodontal wound healing. Chem Eng J. 2025;503:158296.

[DOI]
109. Hu C, Shi J, Zhang F, Lv M, Ge Z, Feng M, et al. Ginsenoside rd-loaded antioxidant polymersomes to regulate mitochondrial homeostasis for bone defect healing in periodontitis. Adv Healthc Mater. 2025;14(4):2403817.

[DOI]
110. Zhu C, Huang K, Li T, Li Y, Jin Y, Li R, et al. Manganese dioxide coupled metal-organic framework as mitophagy regulator alleviates periodontitis through SIRT1-FOXO₃^-BNIP3 signaling axis. Biomaterials. 2025;319:123179.

[DOI]
111. Lam W, Yao Y, Tang C, Wang Y, Yuan Q, Peng L. Bifunctional mesoporous HMUiO-66-NH2 nanoparticles for bone remodeling and ROS scavenging in periodontitis therapy. Biomaterials. 2025;314:122872.

[DOI]
112. Wang X, Ban C, Li X, Wang J, Cao B, Wu W, et al. Bioinspired lipid droplets nanoplatform for periodontitis therapy: Integrated antibacterial, mitochondrial repair, and immunomodulatory functions. Mater Today Bio. 2026;37:102808.

[DOI] [PubMed] [PMC]
113. Ren H, Liu P, Sun Z, Yu Z, Guo H, Cai X, et al. Combined strategy of dual-module cerium nanosystem composite extracellular vesicles regulate ROS in the tissue microenvironment to promote periodontitis recovery. Mater Today Bio. 2026;36:102625.

[DOI] [PubMed] [PMC]
114. Zhang J, Gao B, Ye B, Sun Z, Qian Z, Yu L, et al. Mitochondrial-targeted delivery of polyphenol-mediated antioxidases complexes against pyroptosis and inflammatory diseases. Adv Mater. 2023;35(11):2208571.

[DOI]
115. Gupta M, Dey S, Marbaniang D, Pal P, Ray S, Mazumder B. Grape seed extract: Having a potential health benefits. J Food Sci Technol. 2020;57(4):1205-1215.

[DOI] [PubMed] [PMC]
116. Su K, Yan Y, Huang J, Chen Y, Shang X, Wang X, et al. Mitochondrial-targeted injectable hydrogel for periodontitis therapy via oral immunity and flora regulation. Bioact Mater. 2026;58:348-369.

[DOI] [PubMed] [PMC]
117. Yang S, Zhu Y, Ji C, Zhu H, Lao A, Zhao R, et al. A five-in-one novel MOF-modified injectable hydrogel with thermo-sensitive and adhesive properties for promoting alveolar bone repair in periodontitis: Antibacterial, hemostasis, immune reprogramming, pro-osteo-/ angiogenesis and recruitment. Bioact Mater. 2024;41:239-256.

[DOI]
118. Li S, Chen X, Zhao H, Ma R, Wang Y, Wang G, et al. Targeted antibacterial and mesenchymal stem cell-modulatory hydrogel for periodontitis treatment. Mater Today Bio. 2026;38:103043.

[DOI] [PubMed] [PMC]
119. Yan J, Cui C, Zhou L, Xu Y, Zhang K, Liu K, et al. Mitochondria-targeted nanozyme hydrogel remodels the microenvironment to enhance bone regeneration in diabetes-associated periodontitis. J Nanobiotechnology. 2026;24(1):677.

[DOI] [PubMed] [PMC]
120. Zhang Y, Chen L, Sun R, Lv R, Du T, Li Y, et al. Multienzymatic antioxidant activity of manganese-based nanoparticles for protection against oxidative cell damage. ACS Biomater Sci Eng. 2022;8(2):638-648.

[DOI] [PubMed]
121. Li L, Wu RX, Wang J, Jin R, Zhang XY, Xu M, et al. A multirisk-rescued biomimetic nanozyme against periodontitis via inflammation targeting and microenvironment reprogramming. Chem Eng J. 2025;506:160119.

[DOI]
122. Li T, Shu M, Zhu C, Liu Q, Li Y, Wang R, et al. Triple-combination therapy with a multifunctional yolk–shell nanozyme Au@CeO₂ loaded with dimethyl fumarate for periodontitis. Adv Sci. 2025;12(7):2413891.

[DOI]
123. Tang R, Ren Y, Zhang Y, Yin M, Ren X, Zhu Q, et al. Glucose-driven transformable complex eliminates biofilm and alleviates inflamm-aging for diabetic periodontitis therapy. Mater Today Bio. 2023;20:100678.

[DOI] [PubMed] [PMC]
124. He P, Liu F, Li M, Ren M, Wang X, Deng Y, et al. Mitochondrial calcium ion nanogluttons alleviate periodontitis via controlling mPTPs. Adv Healthc Mater. 2023;12(15):2203106.

[DOI]
125. Bai X, Peng W, Tang Y, Wang Z, Guo J, Song F, et al. An NIR-propelled Janus nanomotor with enhanced ROS-scavenging, immunomodulating and biofilm-eradicating capacity for periodontitis treatment. Bioact Mater. 2024;41:271-292.

[DOI] [PubMed] [PMC]

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Yan X, Hu X, Wei J. Mitochondria-regulating biomaterials for periodontitis therapy: From dysfunction mechanisms to tissue regeneration. BME Horiz. 2027;5:202631. https://doi.org/10.70401/bmeh.2026.0039