Application of gelatin methacryloyl/minocycline-chitosan-nanoparticles composite hydrogel for the treatment of periodontitis

doi:10.7518/hxkq.2023.01.002

Abstract

Abstract:

Objective This study aimed to investigate the feasibility of gelatin methacryloyl (GelMA) hydrogel loa-ded with minocycline-chitosan-nanoparticles (MCN) for the treatment of periodontitis in vitro and vivo. Methods MCN were synthesized by ionic gel method. GelMA/MCN composite hydrogels were prepared by compounding MCN with GelMA hydrogel. The materials were characterized by transmission electron microscope, scanning electron microscopy, and Fourier transform infrared spectroscopy. The degradation behavior and drug release rates of hydrogels were evaluated. The antibacterial activity of GelMA/MCN hydrogel against Porphyromonas gingivalis was detected, and the minimum antibacterial concentration was determined. Biocompatibility and osteogenic experiments were conducted under a simulated periodontitis environment. A rat model of periodontitis was constructed to observe the therapeutic effects of GelMA/MCN hydrogel. Results MCN was successfully synthesized with a particle size of about 80 nm, while the structures of GelMA/MCN had no significant differences from GelMA. MCN and GelMA/MCN released minocycline slowly and steadily. Bacterial growth was completely inhibited when the MCN concentration was higher than or equal to 0.2 mg·mL^-1. GelMA/MCN hydrogels exhibited good biocompatibility at effective antimicrobial concentrations under the simulated periodontitis environment with the enzyme. The in vivo results showed that GelMA/MCN prevented the progression of periodontitis and promoted the repair of bone defects. Conclusion GelMA/MCN composite hydrogel can release minocycline slowly and steadily and has good antibacterial activity and biocompatibility to promote the repair of periodontitis bone defects.

Key words: minocycline, chitosan, hydrogel, sustained drug release, periodontitis

CLC Number:

R 318.08

You Ziying, Wu Yanlin, Sun Yimin, Wang Zhenming, Ye Ling.. Application of gelatin methacryloyl/minocycline-chitosan-nanoparticles composite hydrogel for the treatment of periodontitis[J]. West China Journal of Stomatology, 2023, 41(1): 11-20.

Figures/Tables 7

Fig 1

Fig 2

Fig 3

Fig 4

Fig 5

Fig 6

Fig 7

References 26

1	Jiao J, Jing W, Si Y, et al. The prevalence and severity of periodontal disease in Mainland China: data from the Fourth National Oral Health Survey (2015-2016)[J]. J Clin Periodontol, 2021, 48(2): 168-179.
2	Lu HX, Tao DY, Lo ECM, et al. The 4th national oral health survey in the mainland of China: background and methodology[J]. Chin J Dent Res, 2018, 21(3): 161-165.
3	Zenobia C, Hajishengallis G. Porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis[J]. Virulence, 2015, 6(3): 236-243.
4	Rathnayake N, Gieselmann DR, Heikkinen AM, et al. Salivary Diagnostics-Point-of-Care diagnostics of MMP-8 in dentistry and medicine[J]. Diagnostics (Basel), 2017, 7(1): E7.
5	Mysak J, Podzimek S, Sommerova P, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview[J]. J Immunol Res, 2014, 2014: 476068.
6	Li M, Lv J, Yang Y, et al. Advances of hydrogel therapy in periodontal regeneration—a materials perspective review[J]. Gels, 2022, 8(10): 624.
7	Liu Y, Li T, Sun M, et al. ZIF-8 modified multifunctio-nal injectable photopolymerizable GelMA hydrogel for the treatment of periodontitis[J]. Acta Biomater, 2022, 146: 37-48.
8	Amani H, Mostafavi E, Arzaghi H, et al. Three-dimensional graphene foams: synthesis, properties, biocompa-tibility, biodegradability, and applications in tissue engineering[J]. ACS Biomater Sci Eng, 2019, 5(1): 193-214.
9	Goto R, Nishida E, Kobayashi S, et al. Gelatin methacryloyl-riboflavin (GelMA-RF) hydrogels for bone regene-ration[J]. Int J Mol Sci, 2021, 22(4): 1635.
10	Ma Y, Ji Y, Zhong T, et al. Bioprinting-based PDLSC-ECM screening for in vivo repair of alveolar bone defect using cell-laden, injectable and photocrosslinkable hydrogels[J]. ACS Biomater Sci Eng, 2017, 3(12): 3534-3545.
11	Li N, Xie L, Wu Y, et al. Dexamethasone-loaded zeolitic imidazolate frameworks nanocomposite hydrogel with antibacterial and anti-inflammatory effects for periodontitis treatment[J]. Mater Today Bio, 2022, 16: 100360.
12	Xeroudaki M, Thangavelu M, Lennikov A, et al. A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery[J]. Sci Rep, 2020, 10(1): 16936.
13	Liu S, Jiang N, Chi Y, et al. Injectable and self-healing hydrogel based on chitosan-tannic acid and oxidized hyaluronic acid for wound healing[J]. ACS Biomater Sci Eng, 2022, 8(9): 3754-3764.
14	Ali A, Ahmed S. A review on chitosan and its nanocomposites in drug delivery[J]. Int J Biol Macromol, 2018, 109: 273-286.
15	Yu S, Xu X, Feng J, et al. Chitosan and chitosan coating nanoparticles for the treatment of brain disease[J]. Int J Pharm, 2019, 560: 282-293.
16	Gao P, Xia G, Bao Z, et al. Chitosan based nanoparticles as protein carriers for efficient oral antigen delivery[J]. Int J Biol Macromol, 2016, 91: 716-723.
17	Mohammed MA, Syeda JTM, Wasan KM, et al. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery[J]. Pharmaceutics, 2017, 9(4): E53.
18	朱林, 王聿栋, 董艳梅, 等. 缓释米诺环素的介孔纳米生物玻璃载药系统[J]. 北京大学学报(医学版), 2018, 50(2): 249-255.
	Zhu L, Wang YD, Dong YM, et al. Mesoporous nano-bioactive glass microspheres as a drug delivery system of mino-cycline[J]. J Peking Univ Heal Sci, 2018, 50(2): 249-255.
19	Pan J, Deng J, Luo Y, et al. Thermosensitive hydrogel delivery of human periodontal stem cells overexpressing platelet-derived growth factor-BB enhances alveolar bone defect repair[J]. Stem Cells Dev, 2019, 28(24): 1620-1631.
20	Gupta N, Gupta ND, Goyal L, et al. The influence of smoking on the levels of matrix metalloproteinase-8 and periodontal parameters in smoker and nonsmoker patients with chronic periodontitis: a clinicobiochemical study[J]. J Oral Biol Craniofac Res, 2016, 6(): S39-S43.
21	Guo J, Sun H, Lei W, et al. MMP-8-responsive polyethylene glycol hydrogel for intraoral drug delivery[J]. J Dent Res, 2019, 98(5): 564-571.
22	Imayoshi R, Cho T, Kaminishi H. NO production in RAW264 cells stimulated with Porphyromonas gingivalis extracellular vesicles[J]. Oral Dis, 2011, 17(1): 83-89.
23	Abbas N, Shao GN, Haider MS, et al. Inexpensive Sol-gel synthesis of multiwalled carbon nanotube-TiO₂ hybrids for high performance antibacterial materials[J]. Mater Sci Eng C Mater Biol Appl, 2016, 68: 780-788.
24	Chiappe VB, Gómez MV, Rodríguez C, et al. Subgingivally applied minocycline microgranules in subjects with chronic periodontitis: a randomized clinical and microbiological trial[J]. Acta Odontol Latinoam, 2015, 28(2): 122-131.
25	Deng S, Wang Y, Sun W, et al. Scaling and root planning, and locally delivered minocycline reduces the load of Prevotella intermedia in an interdependent pattern, correlating with symptomatic improvements of chronic periodontitis: a short-term randomized clinical trial[J]. Ther Clin Risk Manag, 2015, 11: 1795-1803.
26	Marchesan J, Girnary MS, Jing L, et al. An experimental murine model to study periodontitis[J]. Nat Protoc, 2018, 13(10): 2247-2267.

[1]	Ye Changchang, Yang He, Huang Ping. Application of intentional replantation in advanced periodontitis involving teeth preservation [J]. West China Journal of Stomatology, 2024, 42(1): 12-18.
[2]	Wang Jun.. Vital pulp therapy of permanent teeth with irreversible pulpitis [J]. West China Journal of Stomatology, 2023, 41(6): 622-627.
[3]	Wang Qintao, Ma Zhiwei, Wang Jinjin.. Personal understanding of the extraction or rescue on severe periodontitis teeth [J]. West China Journal of Stomatology, 2023, 41(6): 635-640.
[4]	Zhang Yanbiao, Wei Meirong, Xia Tianyong, Yin Wenting, Mao Shumei. Association between serum Galectin-3 and periodontitis in patients with type 2 diabetes mellitus [J]. West China Journal of Stomatology, 2023, 41(6): 653-661.
[5]	Cai Hongxuan, Wang Zheng’an, Zhang Zan, Dai Jingyi, Si Weixing, Fu Qiya, Yang Jingwen, Tian Yaguang. Morinda officinalis polysaccharides inhibit the expression and activity of NOD-like receptor thermal protein domain associated protein 3 in inflammatory periodontal ligament cells by upregulating silent information regulator sirtuin 1 [J]. West China Journal of Stomatology, 2023, 41(6): 662-670.
[6]	Jiang Jianhong, Shi Xinglian, He Quanmin, Gao Li, Yang Kun, Wang Taiping, Li Zhezhen, Liu Mei. Correlation between health literacy and life quality in elderly patients with chronic periodontitis [J]. West China Journal of Stomatology, 2023, 41(6): 694-700.
[7]	Lin Li, Li Zhaorong, Jin Yining, Yin Shou-cheng.. Treatment strategies for periodontitis patients with systemic disease [J]. West China Journal of Stomatology, 2023, 41(5): 502-511.
[8]	Zhang Chen, Hou Zhenzhen, Zong Yingrui.. Exploratory research on the probable shared molecular mechanism and transcription factors between chronic periodontitis and chronic obstructive pulmonary disease [J]. West China Journal of Stomatology, 2023, 41(5): 533-540.
[9]	Yang Jingmei, Zhou Ziliang, Wu Yafei, Nie Min. Study on the mechanism of curcumin in the treatment of periodontitis through network pharmacology and mole-cular docking [J]. West China Journal of Stomatology, 2023, 41(2): 157-164.
[10]	Tan Zhongjuan, Luo Yuanyuan, Yang Li. Basic fibroblast growth factor/chitosan derivatives/collagen composite thermosensitive hydrogel promotes perio-dontal tissue regeneration in rats [J]. West China Journal of Stomatology, 2023, 41(1): 21-28.
[11]	Cao Niuben, Liu Xiaomeng, Deng Yu, Liu Xinchan, Xin Yu, Yu Weixian. Reactive oxygen species/c-Jun N-terminal kinase/nuclear factor kappa-B signaling molecules are involved in pe-riodontitis-induced liver injury by regulating apoptosis [J]. West China Journal of Stomatology, 2022, 40(5): 532-540.
[12]	Tao Yufei, He Mengna, Hu Hongyan, Gao Ziwen, Huang Ziang, Li Hui, Li Yuqing, Li Xiaoshu. Correlation study of periodontitis with cognitive impairment [J]. West China Journal of Stomatology, 2022, 40(5): 549-553.
[13]	Qian Jun, Ma Rui, Qu Yan, Deng Shaochun, Duan Yao, Zuo Feifei, Wang Yajie, Wu Yuwei. Use and performance of artificial intelligence applications in the diagnosis of chronic apical periodontitis based on cone beam computed tomography imaging [J]. West China Journal of Stomatology, 2022, 40(5): 576-581.
[14]	Dai Zhenning, Zheng Weihan, Li Shiyu. Receptor activator of nuclear factor-κB ligand and tumor necrosis factor-α promotes osteoclast differentiation through the exosomes of inflammatory periodontal ligament stem cells [J]. West China Journal of Stomatology, 2022, 40(4): 377-385.
[15]	Zeng Xiaoli, Li Shengjiao, Shan Zhengnan, Yin Junhao, Jiang Jirui, Zheng Zhanglong, Li Jia. Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis [J]. West China Journal of Stomatology, 2021, 39(6): 633-641.