负载VEGF@SFNP的微针用于加速口腔黏膜伤口愈合的实验研究

doi:10.19438/j.cjoms.2026.05.004

中国口腔颌面外科杂志 ›› 2026, Vol. 24 ›› Issue (5): 461-469.doi: 10.19438/j.cjoms.2026.05.004

负载VEGF@SFNP的微针用于加速口腔黏膜伤口愈合的实验研究

庞雪菲^1#, 蒋胜杰^2#, 王惠琳¹, 蔡鸣¹

1.上海交通大学医学院附属第九人民医院口腔颅颌面科,上海交通大学口腔医学院,国家口腔医学中心,口腔疾病国家临床医学研究中心,上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011;
2.厦门医学院附属口腔医院,厦门市口腔疾病诊疗重点实验室,福建厦门 361008

收稿日期:2026-03-10 修回日期:2026-05-06 出版日期:2026-09-20 发布日期:2026-10-10
通讯作者: 蔡鸣,E-mail: zidanecm500@126.com
作者简介:庞雪菲（1999—）,女,在读博士研究生,E-mail: pangxfcc@163.com;蒋胜杰（1995—）,男,博士,副主任医师,E-mail: jsj960419@163.com。^#共同第一作者
基金资助:
福建省自然科学基金（2026J0011806）

Experimental study on the use of VEGF@SFNP-loaded microneedles to accelerate oral mucosal wound healing

Pang Xuefei¹, Jiang Shengjie², Wang Huilin¹, Cai Ming¹

1. Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology. Shanghai 200011;
2. Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment. Xiamen 361008, Fujian Province, China

Received:2026-03-10 Revised:2026-05-06 Online:2026-09-20 Published:2026-10-10

摘要/Abstract

摘要： 目的：探讨负载包封血管内皮生长因子（vascular endothelial growth factor,VEGF）的丝素蛋白纳米粒（silk fibroin nanoparticles,SFNP）微针对口腔黏膜伤口的治疗效果。方法：采用甲基丙烯酰化透明质酸（hyaluronic acid methacryloyl,HAMA）制备微针,负载包封VEGF的丝素蛋白纳米粒（VEGF@SFNP）,通过细胞增殖、划痕及成管实验评估其体外促血管再生能力。随后建立大鼠口腔黏膜伤口模型,评价体内促愈合效果。结果：与空白组相比,VEGF@SFNP处理能显著促进细胞增殖能力。划痕实验表明,VEGF@SFNP处理后的细胞迁移能力增强。成管实验表明,VEGF@SFNP组的细胞成血管能力增强。动物实验表明,使用该微针贴片治疗后的大鼠口腔黏膜伤口愈合速度加快。结论：本研究制备的微针贴片可发挥促血管再生作用,显著促进血管再生并加快口腔黏膜伤口愈合速度。

关键词: 口腔黏膜, 微针, 血管内皮生长因子, 纳米颗粒, 血管生成能力

Abstract: PURPOSE: To investigate the therapeutic effect of microneedles loaded with silk fibroin nanoparticles (SFNP) encapsulating vascular endothelial growth factor (VEGF) for oral mucosal wound healing. METHODS: Microneedles were fabricated using methacrylated hyaluronic acid (HAMA) and loaded with VEGF encapsulated in silk fibroin nanoparticles (VEGF@SFNP). The pro-angiogenic capacity was evaluated in vitro through CCK-8 assays, wound healing and tube formation experiments. After that, a rat oral mucosal wound model was established to assess the wound healing efficacy in vivo. RESULTS: CCK-8 assay demonstrated that the proliferation of cells treated with VEGF@SFNP was significantly higher than that in the control group. Wound healing assays indicated enhanced cell migration ability following VEGF@SFNP treatment. Tube formation experiments showed that the VEGF@SFNP group exhibited improved angiogenic capacity. In vivo animal experiments revealed that the microneedle patch treatment accelerated the healing rate of oral mucosal wounds in rats. CONCLUSIONS: The microneedle patch can significantly promote angiogenesis, markedly enhance vascular regeneration, and accelerate the healing process of oral mucosal wounds.

Key words: Oral mucosa, Microneedle, Vascular endothelial growth factor, Nanoparticle, Angiogenic capacity

中图分类号:

R78
R318.08

庞雪菲, 蒋胜杰, 王惠琳, 蔡鸣. 负载VEGF@SFNP的微针用于加速口腔黏膜伤口愈合的实验研究[J]. 中国口腔颌面外科杂志, 2026, 24(5): 461-469.

Pang Xuefei, Jiang Shengjie, Wang Huilin, Cai Ming. Experimental study on the use of VEGF@SFNP-loaded microneedles to accelerate oral mucosal wound healing[J]. China J Oral Maxillofac Surg, 2026, 24(5): 461-469.

参考文献

[1] Xiang YJ, Zhuge P, Qi XL, et al.A cuttlefish ink nanoparticle-reinforced biopolymer hydrogel with robust adhesive and immunomodulatory features for treating oral ulcers in diabetes[J]. Bioact Mater, 2024, 39: 562-581.
[2] Zhang Z, Zhang Q, Gao S, et al.Antibacterial, anti-inflammatory and wet-adhesive poly(ionic liquid)-based oral patch for the treatment of oral ulcers with bacterial infection[J]. Acta Biomater, 2023, 166: 254-265.
[3] Fu H, Yang J, Shen Z, et al.Antibacterial, wet adhesive, and healing-promoting nanosheets for the treatment of oral ulcers[J]. Biomater Sci, 2023, 11(9): 3214-3226.
[4] Rogers RS 3rd. Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders[J]. Semin Cutan Med Surg, 1997, 16(4): 278-283.
[5] Zeng X, Jin X, Zhong L, et al.Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis[J]. Int J Oral Sci, 2022, 14(1): 28.
[6] Ge W, Gao Y, He L, et al.Combination therapy using multifunctional dissolvable hyaluronic acid microneedles for oral ulcers[J]. Int J Biol Macromol, 2023, 251: 126333.
[7] Maymone MBC, Greer RO, Burdine LK, et al.Benign oral mucosal lesions: clinical and pathological findings[J]. J Am Acad Dermatol, 2019, 81(1): 43-56.
[8] Guo X, Zhu T, Yu X, et al.Betamethasone-loaded dissolvable microneedle patch for oral ulcer treatment[J]. Colloids Surf B Biointerfaces, 2023, 222: 113100.
[9] Alaei S, Omidian H.Mucoadhesion and mechanical assessment of oral films[J]. Eur J Pharm Sci, 2021, 159: 105727.
[10] Suharyani I, Fouad Abdelwahab Mohammed A, Muchtaridi M, et al. Evolution of drug delivery systems for recurrent aphthous stomatitis[J]. Drug Des Devel Ther, 2021, 15: 4071-4089.
[11] Cui C, Mei L, Wang D, et al.A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer[J]. Nat Commun, 2023, 14(1): 7707.
[12] Su K, Li J, Wu X, et al.One-step synthesis of hydrogel adhesive with acid-responsive tannin release for diabetic oral mucosa defects healing[J]. Adv Healthc Mater, 2024, 13(9): e2303252.
[13] Meng Y, Li XJ, Li Y, et al.Novel double-layer dissolving microneedles for transmucosal sequential delivery of multiple drugs in the treatment of oral mucosa diseases[J]. ACS Appl Mater Interfaces, 2023, 15(11): 13892-13906.
[14] Li Y, Xiang Y, Chen Y, et al.A natural eumelanin-assisted pullulan/chitosan hydrogel for the management of diabetic oral ulcers[J]. Macromol Biosci, 2025, 25(3): e2400526.
[15] Shi W, Xi Y, Sheng X, et al. Injectable hydrogels for programmable nanoparticle release[J]. Adv Funct Mater, 2025, 35(1):10.1002/adfm.202409796.
[16] Lyu S, Dong Z, Xu X, et al.Going below and beyond the surface: microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration[J]. Bioact Mater, 2023, 27: 303-326.
[17] Xu J, Xu D, Xuan X, et al.Advances of microneedles in biomedical applications[J]. Molecules, 2021, 26(19): 5912.
[18] Li S, Xia D, Prausnitz MR.Efficient drug delivery into skin using a biphasic dissolvable microneedle patch with water-insoluble backing[J]. Adv Funct Mater, 2021, 31(44): 2103359.
[19] Moniz T, Costa Lima SA, Reis S.Marine polymeric microneedles for transdermal drug delivery[J]. Carbohydr Polym, 2021, 266: 118098.
[20] Li Y, Bi D, Hu Z, et al.Hydrogel-forming microneedles with applications in oral diseases management[J]. Materials (Basel), 2023, 16(13): 4805.
[21] Tan P, Chen X, Zhang H, et al.Artificial intelligence aids in development of nanomedicines for cancer management[J]. Semin Cancer Biol, 2023, 89: 61-75.
[22] Lee K, Xue Y, Lee J, et al.A patch of detachable hybrid microneedle depot for localized delivery of mesenchymal stem cells in regeneration therapy[J]. Adv Funct Mater, 2020, 30(23): 2000086.
[23] Wang J, Xu Y, Zheng A, et al.A microneedle platform Co-encapsulating chondral organoids and PpIX for spatiotemporally orchestrated tumor ablation and osteochondral regeneration[J]. Bioact Mater, 2026, 56: 335-352.
[24] Shen T, Xu H, Dai K, et al.Sulfated polysaccharide facilitates macrophage-Treg crosstalk to mitigate chronic inflammation in diabetic wound healing[J]. Bioact Mater, 2026, 55: 640-657.
[25] Xu ZH, Bratlie KM.Click chemistry and material selection for fabrication of hydrogels in tissue engineering applications[J]. ACS Biomater Sci Eng, 2018, 4(7): 2276-2291.
[26] Yu M, Lu Z, Shi Y, et al.Systematic comparisons of dissolving and swelling hyaluronic acid microneedles in transdermal drug delivery[J]. Int J Biol Macromol, 2021, 191: 783-791.
[27] Li W, Li CM, Lu ZF.Vascular endothelial growth factor and its receptor may be one molecular mechanism for androgenetic alopecia[J]. Med Hypotheses, 2009, 72(3): 366-367.
[28] Nguyen NY, Nguyen TNP, Huyen NN, et al.Onto the differences in formulating micro-/nanoparticulate drug delivery system from Thai silk and Vietnamese silk: a critical comparison[J]. Heliyon, 2023, 9(6): e16966.
[29] Li ZB, Liu QQ, Wang HS, et al.Bladder acellular matrix graft reinforced silk fibroin composite scaffolds loaded VEGF with aligned electrospun fibers in multiple layers[J]. ACS Biomater Sci Eng, 2015, 1(4): 238-246.
[30] Du Y, Shi J, Duan R, et al.cRGD peptide incorporated with patchouli alcohol loaded silk fibroin nanoparticles for enhanced targeting of inflammatory sites in colitis[J]. Biomater Adv, 2022, 140: 213069.
[31] Bao L, Hong FF, Li G, et al.Improved performance of bacterial nanocellulose conduits by the introduction of silk fibroin nanoparticles and heparin for small-caliber vascular graft applications[J]. Biomacromolecules, 2021, 22(2): 353-364.
[32] Pham DT, Nguyen DXT, Nguyen NY, et al.Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system[J]. PLoS One, 2024, 19(5): e0303177.
[33] Liu L, Zheng CX, Zhao N, et al.Mesenchymal stem cell aggregation-released extracellular vesicles induce CD31+ EMCN+ vessels in skin regeneration and improve diabetic wound healing[J]. Adv Healthc Mater, 2023, 12(20): e2300019.
[34] Zhu D, Johnson TK, Wang Y, et al.Macrophage M2 polarization induced by exosomes from adipose-derived stem cells contributes to the exosomal proangiogenic effect on mouse ischemic hindlimb[J]. Stem Cell Res Ther, 2020, 11(1): 162.
[35] Cébe-Suarez S, Zehnder-Fjällman A, Ballmer-Hofer K.The role of VEGF receptors in angiogenesis; complex partnerships[J]. Cell Mol Life Sci, 2006, 63(5): 601-615.
[36] Alshehri S, Musleh A.Comparative efficacy of different therapeutic interventions in eustachian tube dysfunctions: a cross-sectional analysis[J]. Diagnostics (Basel), 2024, 14(12): 1229.
[37] Cheng YO, Veettil SK, Syeed MS, et al.Comparative efficacy of therapeutic interventions for the management of recurrent aphthous ulcers: a systematic review and network meta-analysis[J]. J Evid Based Dent Pract, 2023, 23(4): 101918.
[38] Rosa DE, Hapid MH, Hidayat W.Non-healing chronic traumatic ulcer, an entity that can resemble other chronic ulcers[J]. Int Med Case Rep J, 2023, 16: 585-590.
[39] Güneri P, Epstein JB, Bolukbasi G, et al.Neutropenic ulcers in oncology: terminology, diagnosis, and management[J]. Support Care Cancer, 2023, 31(12): 716.
[40] Iglesias-Bartolome R, Uchiyama A, Molinolo AA, et al. Transcriptional signature primes human oral mucosa for rapid wound healing[J]. Sci Transl Med, 2018, 10(451): eaap8798.
[41] Pan Z, Zhang X, Xie W, et al.Revisited and innovative perspectives of oral ulcer: from biological specificity to local treatment[J]. Front Bioeng Biotechnol, 2024, 12: 1335377.
[42] Ma W, Zhang X, Liu Y, et al.Polydopamine decorated microneedles with Fe-MSC-Derived nanovesicles encapsulation for wound healing[J]. Adv Sci (Weinh), 2022, 9(13): e2103317.
[43] Ding YW, Li Y, Zhang ZW, et al.Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment[J]. Bioact Mater, 2024, 38: 95-108.
[44] Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum[J]. Pharmaceutics, 2015, 7(4): 438-470.
[45] Yang J, Liu X, Fu Y, et al.Recent advances of microneedles for biomedical applications: drug delivery and beyond[J]. Acta Pharm Sin B, 2019, 9(3): 469-483.

负载VEGF@SFNP的微针用于加速口腔黏膜伤口愈合的实验研究

Experimental study on the use of VEGF@SFNP-loaded microneedles to accelerate oral mucosal wound healing

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