Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Graphical Abstract
Abstract
Keywords
Electronic Supplementary Material
References
Show full outline
Hide outline
Research Article

Ectopic mineralization-inspired cell membrane-based matrix vesicle analogs for in-depth remineralization of dentinal tubules for treating dentin hypersensitivity

Mingjing Li1, Xiaoran Zheng1, Zhiyun Dong1, Yuyue Zhang1, Wei Wu2, Xingyu Chen3, Chunmei Ding1, Jiaojiao Yang4, Jun Luo1(), Jianshu Li1,4,5()
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China
Key Laboratory for Biorheological Science and Technology of Ministry of Education State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China
College of Medicine, Southwest Jiaotong University, Chengdu 610003, China
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology and Med-X Center for Material, Sichuan University, Chengdu 610041, China
Med-X Center for Material, Sichuan University, Chengdu 610041, China
Show Author Information

Graphical Abstract

View original image Download original image
Ectopic mineralization-inspired matrix vesicle analogs are prepared by employing natural cell membranes to endow mineral precursor nanoparticles with integrated functions for dentin remineralization. The analogs penetrate deep into the interior of dentinal tubules (an unprecedented ~ 200 μm) and efficiently seal exposed dentin via biomineralization to achieve a superior deep occlusion effect for treating dentin hypersensitivity.

Abstract

The invasion of etched dentinal tubules (DTs) by external substances induces dentin hypersensitivity (DH). The deep and compact occlusion of DTs is highly desirable for treating DH but still challenging due to the limited penetrability and mineralization capacities of most current desensitizers. Matrix vesicles (MVs) participate in the regulation of ectopic mineralization. Herein, ectopic MV analogs are prepared by employing natural cell membranes to endow mineral precursors with natural biointerfaces and integrated biofunctions for stimulating dentin remineralization. The analogs quickly access DTs (> 20 μm) in only 5 min and further penetrate deep into the interior of DTs (an extraordinary ~ 200 μm) in 7 days. Both in vitro and in vivo studies confirm that the DTs are efficiently sealed by the newly formed minerals (> 50 μm) with excellent resistance to wear and acid erosion, which is significantly deeper than most reported values. After repair, the microhardness of the damaged dentin can be recovered to those of healthy dentin. For the first time, cell membrane coating nanotechnology is used as a facile and efficient therapy for in-depth remineralization of DTs in treating DH with thorough and long-term effects, which provides insights into their potential for hard tissue repair.

Keywords

bioinspirationdentin remineralizationcell membrane coating nanotechnologyectopic matrix vesiclesmineral precursors

Electronic Supplementary Material

Download File(s)
12274_2022_5376_MOESM1_ESM.pdf (2 MB)

References

[1]

Cui, L.; Houston, D. A.; Farquharson, C.; MacRae, V. E. Characterisation of matrix vesicles in skeletal and soft tissue mineralisation. Bone 2016, 87, 147–158.

Crossref Google Scholar
[2]

Golub, E. E. Biomineralization and matrix vesicles in biology and pathology. Semin. Immunopathol. 2011, 33, 409–417.

Crossref Google Scholar
[3]

Ansari, S.; de Wildt, B. W. M.; Vis, M. A. M.; de Korte, C. E.; Ito, K.; Hofmann, S.; Yuana, Y. Matrix vesicles: Role in bone mineralization and potential use as therapeutics. Pharmaceuticals 2021, 14, 289.

Crossref Google Scholar
[4]

Iwayama, T.; Okada, T.; Ueda, T.; Tomita, K.; Matsumoto, S.; Takedachi, M.; Wakisaka, S.; Noda, T.; Ogura, T.; Okano, T. et al. Osteoblastic lysosome plays a central role in mineralization. Sci. Adv. 2019, 5, eaax0672.

Crossref Google Scholar
[5]

Chen, N. X.; Kircelli, F.; O'Neill, K. D.; Chen, X. M.; Moe, S. M. Verapamil inhibits calcification and matrix vesicle activity of bovine vascular smooth muscle cells. Kidney Int. 2010, 77, 436–442.

Crossref Google Scholar
[6]

Garcia, A. F.; Simão, A. M. S.; Bolean, M.; Hoylaerts, M. F.; Millán, J. L.; Ciancaglini, P.; Costa-Filho, A. J. Effects of GPI-anchored TNAP on the dynamic structure of model membranes. Phys. Chem. Chem. Phys. 2015, 17, 26295–26301.

Crossref Google Scholar
[7]

Hessle, L.; Johnson, K. A.; Anderson, H. C.; Narisawa, S.; Sali, A.; Goding, J. W.; Terkeltaub, R.; Millán, J. L. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc. Natl. Acad. Sci. USA 2002, 99, 9445–9449.

Crossref Google Scholar
[8]

Bäck, M.; Michel, J. B. From organic and inorganic phosphates to valvular and vascular calcifications. Cardiovasc. Res. 2021, 117, 2016–2029.

Crossref Google Scholar
[9]

Li, T. T.; Yu, H. C.; Zhang, D. M.; Feng, T.; Miao, M.; Li, J. W.; Liu, X. H. Matrix vesicles as a therapeutic target for vascular calcification. Front. Cell Dev. Biol. 2022, 10, 825622.

Crossref Google Scholar
[10]

Jing, L. L.; Li, L. H.; Sun, Z.; Bao, Z. Y.; Shao, C.; Yan, J. C.; Pang, Q. W.; Geng, Y.; Zhang, L. L.; Wang, X. D. et al. Role of matrix vesicles in bone-vascular cross-talk. J. Cardiovasc. Pharmacol. 2019, 74, 372–378.

Crossref Google Scholar
[11]

Yan, J. F.; Qin, W. P.; Xiao, B. C.; Wan, Q. Q.; Tay, F. R.; Niu, L. N.; Jiao, K. Pathological calcification in osteoarthritis: An outcome or a disease initiator? Biol. Rev. 2020, 95, 960–985.

Crossref Google Scholar
[12]

Kapustin, A. N.; Shanahan, C. M. Calcium regulation of vascular smooth muscle cell-derived matrix vesicles. Trends Cardiovasc. Med. 2012, 22, 133–137.

Crossref Google Scholar
[13]

Wang, D. Y.; Wang, X. M.; Huang, L.; Pan, Z. Y.; Liu, K. X.; Du, B. B.; Xue, Y.; Li, B.; Zhang, Y.; Wang, H. et al. Unraveling an innate mechanism of pathological mineralization-regulated inflammation by a nanobiomimetic system. Adv. Healthcare Mater. 2021, 10, 2101586.

Crossref Google Scholar
[14]

Zazzeroni, L.; Faggioli, G.; Pasquinelli, G. Mechanisms of arterial calcification: The role of matrix vesicles. Eur. J. Vasc. Endovasc. Surg. 2018, 55, 425–432.

Crossref Google Scholar
[15]

Willems, B. A.; Furmanik, M.; Caron, M. M. J.; Chatrou, M. L. L.; Kusters, D. H. M.; Welting, T. J. M.; Stock, M.; Rafael, M. S.; Viegas, C. S. B.; Simes, D. C. et al. Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling. Sci. Rep. 2018, 8, 4961.

Crossref Google Scholar
[16]

Garcés-Ortíz, M.; Ledesma-Montes, C.; Reyes-Gasga, J. Presence of matrix vesicles in the body of odontoblasts and in the inner third of dentinal tissue: A scanning electron microscopic study. Med. Oral Patol. Oral Cir. Bucal 2013, 18, e537–e541.

Crossref Google Scholar
[17]

Ismail, N. F. A.; Rostam, M. A.; Jais, M. F. M.; Mohd Shafri, M. A.; Ismail, A. F.; Arzmi, M. H. Review: Exploring the potential of nigella sativa for tooth mineralization and periodontitis treatment and its additive effect with doxycycline. IIUM J. Orofacial Health Sci. 2022, 3, 136–146.

Crossref Google Scholar
[18]

Bucchi, C.; Ohlsson, E.; de Anta, J. M.; Woelflick, M.; Galler, K.; Manzanares-Cespedes, M. C.; Widbiller, M. Human amnion epithelial cells: A potential cell source for pulp regeneration? Int. J. Mol. Sci. 2022, 23, 2830.

Crossref Google Scholar
[19]

Yan, W. S.; Jiang, E.; Renteria, C.; Paranjpe, A.; Arola, D. D.; Liao, L.; Ren, X. Y.; Zhang, H. Odontoblast apoptosis and intratubular mineralization of sclerotic dentin with aging. Arch. Oral Biol. 2022, 136, 105371.

Crossref Google Scholar
[20]

West, N.; Seong, J.; Davies, M. Dentine hypersensitivity. Monogr. Oral Sci. 2014, 25, 108–122.

Crossref Google Scholar
[21]

Saeki, K.; Marshall, G. W.; Gansky, S. A.; Parkinson, C. R.; Marshall, S. J. Strontium effects on root dentin tubule occlusion and nanomechanical properties. Dent. Mater. 2016, 32, 240–251.

Crossref Google Scholar
[22]

Chen, Z.; Duan, Y. Y.; Shan, S. Z.; Sun, K. D.; Wang, G.; Shao, C. Y.; Tang, Z. H.; Xu, Z. K.; Zhou, Y. Y.; Chen, Z. et al. Deep and compact dentinal tubule occlusion via biomimetic mineralization and mineral overgrowth. Nanoscale 2022, 14, 642–652.

Crossref Google Scholar
[23]

Akram, Z.; Daood, U.; Aati, S.; Ngo, H.; Fawzy, A. S. Formulation of pH-sensitive chlorhexidine-loaded/mesoporous silica nanoparticles modified experimental dentin adhesive. Mater. Sci. Eng. C 2021, 122, 111894.

Crossref Google Scholar
[24]

de Carvalho, M. A.; Lazari-Carvalho, P. C.; Polonial, I. F.; de Souza, J. B.; Magne, P. Significance of immediate dentin sealing and flowable resin coating reinforcement for unfilled/lightly filled adhesive systems. J. Esthet. Restor. Dent. 2021, 33, 88–98.

Crossref Google Scholar
[25]

Li, C.; Lu, D. Y.; Deng, J. J.; Zhang, X.; Yang, P. Amyloid-like rapid surface modification for antifouling and in-depth remineralization of dentine tubules to treat dental hypersensitivity. Adv. Mater. 2019, 31, 1903973.

Crossref Google Scholar
[26]

Bandarra, S.; Mascarenhas, P.; Luís, A. R.; Catrau, M.; Bekman, E.; Ribeiro, A. C.; Félix, S.; Caldeira, J.; Barahona, I. In vitro and in silico evaluations of resin-based dental restorative material toxicity. Clin. Oral Invest. 2020, 24, 2691–2700.

Crossref Google Scholar
[27]

Bae, J. H.; Kim, Y. K.; Myung, S. K. Desensitizing toothpaste versus placebo for dentin hypersensitivity: A systematic review and meta-analysis. J. Clin. Periodontol. 2015, 42, 131–141.

Crossref Google Scholar
[28]

Fang, R. H.; Kroll, A. V.; Gao, W. W.; Zhang, L. F. Cell membrane coating nanotechnology. Adv. Mater. 2018, 30, 1706759.

Crossref Google Scholar
[29]

Wang, Y.; Zhang, K.; Qin, X.; Li, T. H.; Qiu, J. H.; Yin, T. Y.; Huang, J. L.; McGinty, S.; Pontrelli, G.; Ren, J. et al. Biomimetic nanotherapies: Red blood cell based core–shell structured nanocomplexes for atherosclerosis management. Adv. Sci. 2019, 6, 1900172.

Crossref Google Scholar
[30]

Sun, L. Z.; He, L. B.; Wu, W.; Luo, L.; Han, M. Y.; Liu, Y. F.; Shi, S. J.; Zhong, K. J.; Yang, J. J.; Li, J. Y. Fibroblast membrane-camouflaged nanoparticles for inflammation treatment in the early stage. Int. J. Oral Sci. 2021, 13, 39.

Crossref Google Scholar
[31]

Luk, B. T.; Hu, C. M.; Fang, R. H.; Dehaini, D.; Carpenter, C.; Gao, W. W.; Zhang, L. F. Interfacial interactions between natural RBC membranes and synthetic polymeric nanoparticles. Nanoscale 2014, 6, 2730–2737.

Crossref Google Scholar
[32]

Narain, A.; Asawa, S.; Chhabria, V.; Patil-Sen, Y. Cell membrane coated nanoparticles: Next-generation therapeutics. Nanomedicine 2017, 12, 2677–2692.

Crossref Google Scholar
[33]

Yan, H. Z.; Shao, D.; Lao, Y. H.; Li, M. Q.; Hu, H. Z.; Leong, K. W. Engineering cell membrane-based nanotherapeutics to target inflammation. Adv. Sci. 2019, 6, 1900605.

Crossref Google Scholar
[34]

Dong, Z. Y.; Ke, X.; Tang, S. X.; Wu, S.; Wu, W.; Chen, X. Y.; Yang, J. J.; Xie, J.; Luo, J.; Li, J. S. A stable cell membrane-based coating with antibiofouling and macrophage immunoregulatory properties for implants at the macroscopic level. Chem. Mater. 2021, 33, 7994–8006.

Crossref Google Scholar
[35]

Kaestner, L.; Bogdanova, A.; Egee, S. Calcium channels and calcium-regulated channels in human red blood cells. Adv. Exp. Med. Biol. 2020, 1131, 625–648.

Crossref Google Scholar
[36]

Bogdanova, A.; Makhro, A.; Wang, J.; Lipp, P.; Kaestner, L. Calcium in red blood cells—A perilous balance. Int. J. Mol. Sci. 2013, 14, 9848–9872.

Crossref Google Scholar
[37]

Tziakas, D. N.; Chalikias, G.; Pavlaki, M.; Kareli, D.; Gogiraju, R.; Hubert, A.; Böhm, E.; Stamoulis, P.; Drosos, I.; Kikas, P. et al. Lysed erythrocyte membranes promote vascular calcification: Possible role of erythrocyte-derived nitric oxide. Circulation 2019, 139, 2032–2048.

Crossref Google Scholar
[38]

Yao, W.; Ma, L.; Chen, R. H.; Xie, Y. M.; Li, B., Zhao, B. Guided tissue remineralization and its effect on promoting dentin bonding. Front. Mater. 2022, 9, 1026522.

Crossref Google Scholar
[39]

Tang, S. X.; Dong, Z. Y.; Ke, X.; Luo, J.; Li, J. S. Advances in biomineralization-inspired materials for hard tissue repair. Int. J. Oral Sci. 2021, 13, 42.

Crossref Google Scholar
[40]

Lotsari, A.; Rajasekharan, A. K.; Halvarsson, M.; Andersson, M. Transformation of amorphous calcium phosphate to bone-like apatite. Nat. Commun. 2018, 9, 4170.

Crossref Google Scholar
[41]

Mu, Z.; Kong, K. R.; Jiang, K.; Dong, H. L.; Xu, X. R.; Liu, Z. M.; Tang, R. K. Pressure-driven fusion of amorphous particles into integrated monoliths. Science 2021, 372, 1466–1470.

Crossref Google Scholar
[42]

He, L. B.; Hao. Y.; Zhen, L.; Liu, H. L.; Shao, M. Y.; Xu, X.; Liang, K. N.; Gao, Y.; Yuan, H.; Li, J. S. et al. Biomineralization of dentin. J. Struct. Biol. 2019, 207, 115–122.

Crossref Google Scholar
[43]

Sun, X. Y.; Xu, C.; Wu, G.; Ye, Q. S.; Wang, C. N. Poly(lactic-co-glycolic acid): Applications and future prospects for periodontal tissue regeneration. Polymers 2017, 9, 189.

Crossref Google Scholar
[44]

Tjäderhane, L.; Carrilho, M. R.; Breschi, L.; Tay, F. R.; Pashley, D. H. Dentin basic structure and composition—An overview. Endod. Top. 2009, 20, 3–29.

Crossref Google Scholar
[45]

Shapiro, I. M.; Landis, W. J.; Risbud, M. V. Matrix vesicles: Are they anchored exosomes? Bone 2015, 79, 29–36.

Crossref Google Scholar
[46]

Carda, C.; Peydró, A. Ultrastructural patterns of human dentinal tubules, odontoblasts processes and nerve fibres. Tissue Cell 2006, 38, 141–150.

Crossref Google Scholar
[47]

Tan, S. W.; Wu, T. T.; Zhang, D.; Zhang, Z. P. Cell or cell membrane-based drug delivery systems. Theranostics 2015, 5, 863–881.

Crossref Google Scholar
[48]

Wang, Z.; Ouyang, Y.; Wu, Z. F.; Zhang, L. Q.; Shao, C. Y.; Fan, J. Y.; Zhang, L.; Shi, Y.; Zhou, Z. H.; Pan, H. H. et al. A novel fluorescent adhesive-assisted biomimetic mineralization. Nanoscale 2018, 10, 18980–18987.

Crossref Google Scholar
[49]

Priante, G.; Mezzabotta, F.; Cristofaro, R.; Quaggio, F.; Ceol, M.; Gianesello, L.; Del Prete, D.; Anglani, F. Cell death in ectopic calcification of the kidney. Cell Death Dis. 2019, 10, 466.

Crossref Google Scholar
[50]

Wu, C. Y.; Martel, J.; Young, J. D. Ectopic calcification and formation of mineralo-organic particles in arteries of diabetic subjects. Sci. Rep. 2020, 10, 8545.

Crossref Google Scholar
[51]

Liang, K. N.; Weir, M. D.; Xie, X. J.; Wang, L.; Reynolds, M. A.; Li, J. Y.; Xu, H. H. K. Dentin remineralization in acid challenge environment via PAMAM and calcium phosphate composite. Dent. Mater. 2016, 32, 1429–1440.

Crossref Google Scholar
Nano Research
Volume 16 Issue 5,
May 2023
Pages 7269-7279
DOI: 10.1007/s12274-023-5376-1
Cite this article:
Li M, Zheng X, Dong Z, et al. Ectopic mineralization-inspired cell membrane-based matrix vesicle analogs for in-depth remineralization of dentinal tubules for treating dentin hypersensitivity. Nano Research, 2023, 16(5): 7269-7279. https://doi.org/10.1007/s12274-023-5376-1
Topics:
Biomaterials Cell membranes
Metrics & Citations  
Article History
Copyright
Return