Abstract
The socket preservation requires special structures for tissue engineering scaffolds. In this study, we developed a kind of Janus nanocomposite hydrogels with antibacterial property, soft tissue barrier function and bone repairing ability using a penetration cross-linking method. The hydrogels were constructed by permeating oxidized sodium alginate solution into a highly viscous nano-hydroxyapatite-contained carboxymethyl chitosan suspension. Through this process, the Janus structure was fabricated. The dense, smooth top-surface showed a significant barrier function against fibroblast cells, while its loose, porous bottom-surface could support bone regeneration with nano hydroxyapatite. And in order to inhibit periodontitis-related bacteria, an antibacterial agent, metronidazole, was combined into the hydrogels. The CAH4M hydrogel showed antibacterial efficiencies of 82% against S. mutans and 93% against P. gingivalis. The hemolysis ratio was less than 5%, and there was no evident cytotoxicity, demonstrating the good biocompatibility. The in vivo anti-infection and bone repairing properties of the hydrogels were verified by a rat model of infected extraction socket. Based on the above results, this study provided a promising strategy to prepare tissue engineering scaffolds that meet clinical requirements for socket preservation and prevention of infection.
摘要
拔牙窝位点保存需要特殊的组织工程支架. 在本研究中, 我们采 用渗透交联的方法开发了一种具有抵抗成纤维细胞入侵、牙槽骨保存 和抗菌的多功能Janus结构复合水凝胶. 通过将氧化的海藻酸钠溶液渗 透到含有羧甲基壳聚糖的高黏性纳米羟基磷灰石悬浮液中来构建水凝 胶. 通过这个过程制备出的Janus结构水凝胶, 其致密、光滑的上表面 对成纤维细胞显示出显著的屏障功能, 而其疏松、多孔的下表面可以 在纳米羟基磷灰石的作用下进行有效的牙槽骨保存, 并且在水凝胶中 加入了一种抗菌剂甲硝唑, 有效抑制了牙周炎相关细菌. 其中最优组 CAH4M水凝胶对变形链球菌和牙龈卟啉单胞菌的抗菌效率分别为 82%和93%, 溶血率小于5%, 没有明显的细胞毒性.
Article PDF
Similar content being viewed by others
References
Buser D, Chappuis V, Belser UC, et al. Implant placement post extraction in esthetic single tooth sites: When immediate, when early, when late? Periodontol 2000, 2000, 73: 84–102
Moran IJ, Richardson L, Heliotis M, et al. A bleeding socket after tooth extraction. BMJ, 2017, 357: j1217
Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet, 2005, 366: 1809–1820
Araújo MG, Silva CO, Souza AB, et al. Socket healing with and without immediate implant placement. Periodontol 2000, 2019, 79: 168–177
Araújo MG, Dias DR, Matarazzo F. Anatomical characteristics of the alveolar process and basal bone that have an effect on socket healing. Periodontol 2000, 2023, 93: 277–288
Johnson K. A study of the dimensional changes occurring in the maxilla following tooth extraction. Aust Dent J, 1969, 14: 241–244
Araújo MG, Lindhe J. Ridge alterations following tooth extraction with and without flap elevation: An experimental study in the dog. Clin Oral ImPlants Res, 2009, 20: 545–549
Cardaropoli G, Araújo M, Hayacibara R, et al. Healing of extraction sockets and surgically produced—augmented and non-augmented—defects in the alveolar ridge. An experimental study in the dog. J Clinic Periodontol, 2005, 32: 435–440
Fickl S, Zuhr O, Wachtel H, et al. Tissue alterations after tooth extraction with and without surgical trauma: A volumetric study in the beagle dog. J Clinic Periodontol, 2008, 35: 356–363
Schropp L, Wenzel A, Kostopoulos L, et al. Bone healing and soft tissue contour changes following single-tooth extraction: A clinical and radiographic 12-month prospective study. Int J Periodon Rest Dent, 2003, 23: 313–323
Avila-Ortiz G, Chambrone L, Vignoletti F. Effect of alveolar ridge preservation interventions following tooth extraction: A systematic review and meta-analysis. J Clinic Periodontol, 2019, 46: 195–223
Alfonsi F, Borgia V, Iezzi G, et al. Molecular, cellular and pharmaceutical aspects of filling biomaterials during the management of extraction sockets. Curr Pharm Biotechnol, 2017, 18: 64–75
Yamamichi N, Itose T, Neiva R, et al. Long-term evaluation of implant survival in augmented sinuses: A case series. Int J Periodon Rest Dent, 2008, 28: 163–169
Pikdöken L, Gürbüzer Bı, Küçükodacı Z, et al. Scintigraphic, histologic, and histomorphometric analyses of bovine bone mineral and autogenous bone mixture in sinus floor augmentation: A randomized controlled trial—Results after 4 months of healing. J Oral Maxillofac Surg, 2011, 69: 160–169
Maria Soardi C, Spinato S, Zaffe D, et al. Atrophic maxillary floor augmentation by mineralized human bone allograft in sinuses of different size: An histologic and histomorphometric analysis. Clin Oral ImPlants Res, 2011, 22: 560–566
Kühl S, Götz H, Hansen T, et al. Three-dimensional analysis of bone formation after maxillary sinus augmentation by means of micro-computed tomography: A pilot study. Int J Oral Maxill Implan, 2010, 25: 930–938
Gu J, Jiao K, Li J, et al. Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction. Bioactive Mater, 2022, 15: 68–81
Ou M, Huang X. Influence of bone formation by composite scaffolds with different proportions of hydroxyapatite and collagen. Dent Mater, 2021, 37: e231–e244
Tian B, Li X, Zhang J, et al. A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair. Int J Oral Sci, 2022, 14: 1–8
Li X, Li S, Qi H, et al. Early healing of alveolar bone promoted by microRNA-21-loaded nanoparticles combined with Bio-Oss particles. Chem Eng J, 2020, 401: 126026
Rosenquist B, Grenthe B. Immediate placement of implants into extraction sockets: Implant survival. ImPlant Dent, 1996, 5: 297
Quirynen M, Gijbels F, Jacobs R. An infected jawbone site compromising successful osseointegration. Periodontol 2000, 2003, 33: 129–144
Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers, 2017, 3: 17038
Wu Y, Lin Y, Cong Z, et al. Peptide polymer-doped cement acting as an effective treatment of MRSA-infected chronic osteomyelitis. Adv Funct Mater, 2022, 32: 2107942
Vellayappan MV, Duarte F, Sollogoub C, et al. Fabrication of architectured biomaterials by multilayer co-extrusion and additive manufacturing. Adv Funct Mater, 2023, 33: 2301547
Ko KW, Park SY, Lee EH, et al. Integrated bioactive scaffold with polydeoxyribonucleotide and stem-cell-derived extracellular vesicles for kidney regeneration. ACS Nano, 2021, 15: 7575–7585
Ovsianikov A, Khademhosseini A, Mironov V. The synergy of scaffold-based and scaffold-free tissue engineering strategies. Trends Biotechnol, 2018, 36: 348–357
Wu Y, Chen K, Wang J, et al. Host defense peptide mimicking antimicrobial amino acid polymers and beyond: Design, synthesis and biomedical applications. Prog Polym Sci, 2023, 141: 101679
Zhong C, Wu Y, Lin H, et al. Advances in the antimicrobial treatment of osteomyelitis. Compos Part B-Eng, 2023, 249: 110428
Lee SS, Du X, Kim I, et al. Scaffolds for bone-tissue engineering. Matter, 2022, 5: 2722–2759
Zhang L, Hu C, Sun M, et al. Bodipy-functionalized natural polymer coatings for multimodal therapy of drug-resistant bacterial infection. Adv Sci, 2023, 10: 2300328
Zhang L, Yang Y, Xiong YH, et al. Infection-responsive long-term antibacterial bone plates for open fracture therapy. Bioactive Mater, 2023, 25: 1–12
Wu J, Pan Z, Zhao ZY, et al. Anti-swelling, robust, and adhesive extracellular matrix-mimicking hydrogel used as intraoral dressing. Adv Mater, 2022, 34: 2200115
Liu F, Liu X, Chen F, et al. Mussel-inspired chemistry: A promising strategy for natural polysaccharides in biomedical applications. Prog Polym Sci, 2021, 123: 101472
Upadhyaya L, Singh J, Agarwal V, et al. Biomedical applications of carboxymethyl chitosans. Carbohydrate Polyms, 2013, 91: 452–466
Chen L, Peng M, Zhou J, et al. Supramolecular photothermal cascade nano-reactor enables photothermal effect, cascade reaction, and in situ hydrogelation for biofilm-associated tooth-extraction wound healing. Adv Mater, 2023, 35: 2301664
Emami Z, Ehsani M, Zandi M, et al. Controlling alginate oxidation conditions for making alginate-gelatin hydrogels. Carbohydrate Polyms, 2018, 198: 509–517
Xiong YH, Zhang L, Xiu Z, et al. Derma-like antibacterial polysaccharide gel dressings for wound care. Acta Biomater, 2022, 148: 119–132
Jiang SJ, Wang MH, Wang ZY, et al. Radially porous nanocomposite scaffolds with enhanced capability for guiding bone regeneration in vivo. Adv Funct Mater, 2022, 32: 2110931
Wei S, Ma JX, Xu L, et al. Biodegradable materials for bone defect repair. Military Med Res, 2020, 7: 54
Kong HJ, Alsberg E, Kaigler D, et al. Controlling degradation of hydrogels via the size of crosslinked junctions. Adv Mater, 2004, 16: 1917–1921
Lockhart PB, Brennan MT, Sasser HC, et al. Bacteremia associated with toothbrushing and dental extraction. Circulation, 2008, 117: 3118–3125
Sun Z, Ma L, Sun X, et al. The overview of antimicrobial peptide-coated implants against oral bacterial infections. Aggregate, 2023, 4: e309
Kuboniwa M, Houser JR, Hendrickson EL, et al. Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection. Nat Microbiol, 2017, 2: 1493–1499
Acknowledgements
This work was supported by the National Key Research and Development Program of China (2022YFC2403200), the National Natural Science Foundation of China (52221006, 52293382, 52122304, and 52073024), the National High Level Hospital Clinical Research Funding (2023-NHLHCRF-YGJH-ZR-02), and Beijing Outstanding Young Scientist Program (BJJWZYJH01201910010024).
Author information
Authors and Affiliations
Contributions
Author contributions Xu FJ, Duan S, and Sun Q proposed the idea of this work. Shi T wrote the manuscript with support from Song W, Sun M, and Wu R. Xiong YH and Song W performed the experiments and organized the figures. The manuscript was discussed and revised by all authors.
Corresponding authors
Ethics declarations
Conflict of interest The authors declare that they have no conflict of interest.
Additional information
Supplementary information Experimental details and supporting data are available in the online version of the paper.
Tailong Shi received his BS degree in functional materials from Beijing University of Chemical Technology (2022). He is currently a master candidate at Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology under the supervision of Prof. Fu-Jian Xu. His research activities focus on antibacterial dressings.
Yan-Hua Xiong received his PhD degree in materials science and engineering from Beijing University of Chemical Technology (2022). He is currently a technical manager at IMEIK Technology Development Co., Ltd. His research activities focus on the construction of tissue scaffolds and the regeneration of soft tissues.
Qiang Sun graduated from the Dental School of China Medical University and is an associate professor of Peking University. He attended the international postdoc scholarship at the University of Pennsylvania Program. His research interests include but not limited to bone osteogenesis with innovative methods and antibiotic therapy with medical dressings loaded by medicine.
Shun Duan graduated from Qingdao University of Science and Technology, majoring in pharmaceutical engineering/English, with a bachelor’s degree of engineering and a bachelor’s degree of arts. In 2014, he graduated from Beijing University of Chemical Technology with a PhD degree majoring in materials science and engineering. His main research interest is antibacterial materials, which combines active polymerization with natural polymers. He performs a series of researches in novel antimicrobial materials, controllable surface functionalization of medical materials and industrialization of antimicrobial materials.
Fu-Jian Xu obtained PhD degree in biomolecular engineering in 2006 from the National University of Singapore (NUS). After two-years of post-doctoral work as a Lee Kuan Yew Postdoctoral Fellow in NUS, he joined Beijing University of Chemical Technology in 2009. His research interests focus on functional biomacromolecules.
Supporting Information
40843_2023_2721_MOESM1_ESM.pdf
Polysaccharide-based antibacterial nanocomposite hydrogels with Janus structure for treatment of infected extraction socket
Rights and permissions
About this article
Cite this article
Shi, T., Xiong, YH., Song, W. et al. Polysaccharide-based antibacterial nanocomposite hydrogels with Janus structure for treatment of infected extraction socket. Sci. China Mater. (2024). https://doi.org/10.1007/s40843-023-2721-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s40843-023-2721-5