目的 以生物相容性良好且活性位点丰富的生物材料为基底,接枝黏附基团与功能因子,构建口腔用复合纳米膜,研究其力学与生物学特性,为口腔黏膜创面治疗提供新途径。方法 通过溶液旋涂法制备以甲基丙烯酰化明胶(GelMA)、多巴胺(DA)、抗菌多肽(AMP)、钙离子(Ca2+)为基体材料的复合纳米膜;运用膨胀应力与拉伸应力测试评估力学性能,通过细胞活死染色、CCK-8增殖实验检测生物安全性,采用平板抑菌实验及扫描电镜测定复合膜的体外抗菌能力,采用凝血板法分析复合纳米膜的体外止血性能,开展体外黏附测试并考察其湿黏接能力。结果 选定GelMA、DA、AMP、Ca2+为基体材料,以溶液旋涂法制备出独立纳米薄膜。其耐受压力达(6.75±0.25)kPa,高于人体血压,最大耐拉伸应力 4 MPa,接近人体软组织;细胞实验证实具有良好生物安全性;2 h内杀菌效率超 99%;在模拟口腔湿润环境下展现湿黏接性能出色。结论 成功构建兼具湿黏接、抗菌及止血性能的口腔用复合纳米膜,为口腔黏膜创面封闭与修复提供创新方案。
Abstract
Objective To construct a composite nano-film for oral use based on biocompatible and bioactive materials with abundant active sites grafted with adhesion groups and functional factors, and to provide a new approach for the treatment of oral mucosal wounds through studying its mechanical and biological properties. Methods A composite nanofilm was prepared using methacrylated gelatin (GelMA), dopamine (DA), antimicrobial peptides (AMP), and calcium ions (Ca2+) as the base materials by solution spin coating. The mechanical properties were evaluated by tensile stress and swelling stress tests. The biocompatibility was detected by cell viability and CCK-8 proliferation assays. The in vitro antibacterial ability of the composite films was determined by plate inhibition tests and SEM. The in vitro hemostatic performance of the composite nanofilms was analyzed by the platelet method. The wet adhesion ability was investigated by in vitro adhesion tests. Results GelMA, DA, AMP and Ca2+ were selected as the base materials, and an independent nanofilm was fabricated by solution spin-coating method. The pressure tolerance reached (6.75±0.25) kPa, which was higher than human blood pressure. The maximum tensile stress was 4 MPa, close to that of human soft tissues. Cell experiments confirmed good biocompatibility. The bactericidal efficiency exceeded 99% within 2 h. It exhibited excellent wet adhesion performance in simulated oral moist environment. Conclusions A composite nanofilm with wet adhesion, antibacterial and hemostatic properties for oral use has been successfully constructed for oral use, providing an innovative solution for the closure and repair of oral mucosal wounds.
关键词
口腔用复合纳米膜 /
口腔黏膜创面 /
甲基丙烯酰化明胶 /
多巴胺 /
湿黏接
Key words
oral nanofilm /
oral mucosal wound /
methacrylated gelatin /
dopamine /
wet adhesion
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Toma A I, Fuller J M, Willett N J, et al. Oral wound healing models and emerging regenerative therapies[J]. Transl Res, 2021, 236:17-34.
[2] Nikoloudaki G, Creber K, Hamilton D W. Wound healing and fibrosis: a contrasting role for periostin in skin and the oral mucosa[J]. Am J Physiol Cell Physiol, 2020,318(6):C1065-C1077.
[3] 陈谦明.口腔黏膜病学[M].北京:人民卫生出版社,2016:12-197.
[4] Kong X, Fu J, Shao K, et al. Biomimetic hydrogel for rapid and scar-free healing of skin wounds inspired by the healing process of oral mucosa[J]. Acta Biomater,2019,100:255-269.
[5] Chen Y, Gao B, Cai W, et al. Oral mucosa: anti-inflammatory function, mechanisms, and applications[J]. J Mater Chem B, 2025,13(13):4059-4072.
[6] Kim Y J, Carvalho F C, Souza J A,et al. Topical application of the lectin artin M accelerates wound healing in rat oral mucosa by enhancing TGF-β and VEGF production[J]. Wound Repair Regen, 2013, 21(3):456-463.
[7] Lau C B, Smith G P. Recurrent aphthous stomatitis: a comprehensive review and recommendations on therapeutic options[J]. Dermatol Ther,2022,35(6):e15500.
[8] Liu H, Tan L, Fu G,et al. Efficacy of topical intervention for recurrent aphthous stomatitis: a network meta-analysis[J]. Medicina (Kaunas),2022,58(6):771.
[9] Bayda S, Adeel M, Tuccinardi T, et al. The history of nanoscience and nanotechnology: from chemical-physical applications to nanomedicine[J]. Molecules, 2019,25(1):112.
[10] Blanco-F B, Castaño O, Mateos M Á, et al. Nanotechnology approaches in chronic wound healing[J]. Adv Wound Care (New Rochelle),2021,234-256.
[11] 杨汇尚.用于难愈伤口修复的功能化纳米膜的制备及其性能研究[D].广州:华南理工大学, 2020.
[12] Tripathy D B, Gupta A. Nanomembranes-affiliated water remediation: chronology, properties, classification, challenges and future prospects[J]. Membranes (Basel),2023,13(8):713.
[13] Krysztofik A, Warzajtis M, Pochylski M. Multi-responsive poly-catecholamine nanomembranes[J]. Nanoscale,2024,16(34):16227-16237.
[14] Deng Daokun,Li Xuan,Zhang JiuJiu,et al. Biotin-avidin system-based delivery enhances the therapeutic performance of MSC-derived exosomes.[J].ACS Nano,2023,17(9):8530-8550.
[15] Fu Y, Yang L, Zhang J, et al. Polydopamine antibacterial materials[J]. Mater Horiz, 2021, 8(6):1618-1633.
[16] Yazdi M K, Zare M, Khodadadi A, et al. Polydopamine biomaterials for skin regeneration[J]. ACS Biomater Sci Eng,2022,8(6):2196-2219.
[17] Zheng P, Ding B, Li G. Polydopamine-incorporated nanoformulations for biomedical applications[J]. Macromol Biosci,2020,20(12):e2000228.
[18] El Yakhlifi S, Ball V. Polydopamine as a stable and functional nanomaterial[J]. Colloids Surf B Biointerfaces,2020,186:110719.
[19] Xu Z, Wang T, Liu J. Recent development of polydopamine anti-bacterial nanomaterials[J]. Int J Mol Sci,2022,23(13):7278.
[20] Moreira J, Vale A C, Alves NM. Spin-coated freestanding films for biomedical applications[J]. J Mater Chem B,2021,9(18):3778-3799.
[21] Powojska A, Mystkowski A, Gundabattini E, et al. Spin-coating fabrication method of PDMS/NdFeB composites using chitosan/PCL coating[J]. Materials (Basel),2024,17(9):1973.
[22] Yin Z, Tian B, Zhu Q, Duan C. Characterization and application of PVDF and its copolymer films prepared by spin-coating and langmuir-blodgett method[J]. Polymers (Basel), 2019, 11(12):2033.
[23] Hernandez G, Messina A, Kattan E. Invasive arterial pressure monitoring: much more than mean arterial pressure[J]. Intensive Care Med,2022,48(10):1495-1497.
[24] Han L, Lu X, Liu K, et al. Mussel-inspired adhesive and tough hydrogel based on nanoclay confined dopamine polymerization[J]. ACS Nano,2017,11(3):2561-2574.
[25] Li Y, Yu P, Wen J, et al.Nanozyme-based stretchable hydrogel of low hysteresis with antibacterial and antioxidant dual functions for closely fitting and wound healing in movable parts[J].Adv Funct Mater,2022, 32(13): 2110720.
[26] He Y, Liu K, Guo S, et al. Multifunctional hydrogel with reactive oxygen species scavenging and photothermal antibacterial activity accelerates infected diabetic wound healing[J]. Acta Biomater,2023,155:199-217.
[27] Chen Z, Luo L, Luo K, et al. Bioactive materials in periodontal regeneration[J]. Chin J Biotechnol, 2024, 40(2): 378-390.
PDF(4504 KB)
