Zinc oxide and ellagic acid wound dressing enhances FGF-2 and VEGF expression during early excisional wound healing
DOI:
https://doi.org/10.1590/1678-7765-2026-0544Keywords:
Zinc oxide, Ellagic acid, Wound dressing, Fibroblast growth factor-2, Vascular endothelial growth factor, Wound healingAbstract
Introduction: Zinc oxide-based periodontal dressings are widely used to protect surgical wounds, but conventional formulations have limited anti-inflammatory activity. Ellagic acid is a natural polyphenol with antioxidant and anti-inflammatory properties that may improve local wound-healing response. Objective: This study evaluated the effect of a zinc oxide and ellagic acid wound dressing on fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) expression during early excisional wound healing. Methodology: Standardized 10×10 mm dorsal excision wounds were created in 20 male Wistar rats. Control wounds received a zinc oxide dressing, whereas treatment wounds received zinc oxide combined with ellagic acid and coconut fatty acids. Tissue samples were collected on days 3 and 7. FGF-2 and VEGF expression were evaluated using immunohistochemistry and quantified as the mean number of positively stained cells in ten microscopic fields. Data were assessed for normality and homogeneity of variance and analyzed using two-way ANOVA to evaluate the effects of dressing type, observation time, and their interaction, followed by Tukey's post hoc test. Results: FGF-2 and VEGF expression were higher in the zinc oxide and ellagic acid groups than in the corresponding control groups on both days 3 and 7, with the highest expression observed in the treatment group on day 7. Two-way ANOVA showed significant effects of dressing type and observation time, as well as significant dressing × time interactions for both FGF-2 and VEGF. Conclusions: These findings indicate that the treatment-associated increase in growth factor expression was more pronounced on day 7. Zinc oxide and ellagic acid wound dressing increased FGF-2 and VEGF expression during early excisional wound healing, particularly on day 7. These findings suggest that adding ellagic acid to a zinc oxide-based dressing may support fibroblast-related tissue repair and angiogenic activity during the proliferative phase of wound healing.
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1Goldberg SR, Diegelmann RF. Basic science of wound healing. In: Dieter R, Dieter R Jr, Dieter R III, Nanjundappa A, editors. Critical Limb Ischemia. Springer: Cham; 2017. p. 131-6. doi: 10.1007/978-3-319-31991-9_14
» https://doi.org/10.1007/978-3-319-31991-9_14
2Wallace HA, Basehore BM, Zito PM. Wound healing phases. [Updated 2023 Jun 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-.
3Cho YD, Kim KH, Lee YM, Ku Y, Seol YJ. Periodontal wound healing and tissue regeneration: a narrative review. Pharmaceuticals (Basel). 2021;14(5):456. doi: 10.3390/ph14050456
» https://doi.org/10.3390/ph14050456
4Bezawada NR, Bali S, Aggarwal P, Arora S. Periodontal dressings: a review. Santosh Univ J Health Sci. 2020;6(1):5–9. doi: 10.18231/j.sujhs.2020.002
» https://doi.org/10.18231/j.sujhs.2020.002
5Budisidharta Y, Syaify A, Lastianny SP. The effects of zinc oxide non-eugenol and cellulose as periodontal dressings on open wounds after periodontal surgery. Dent J (Majalah Kedokteran Gigi). 2020;53(1):45–9. doi: 10.20473/j.djmkg.v53.i1.p45-49
» https://doi.org/10.20473/j.djmkg.v53.i1.p45-49
6Mitra D, Kashid RV, Shetty G, Bhanushali N. Evaluation and comparison of postoperative healing with and without periodontal dressing in patients undergoing periodontal therapy: a systematic review. J Interdiscip Dent. 2024;14(3):147-56. doi: 10.4103/jid.jid_40_24
» https://doi.org/10.4103/jid.jid_40_24
7Ríos JL, Giner RM, Marín M, Recio MC. A pharmacological update of ellagic acid. Planta Med. 2018;84(15):1068–93. doi: 10.1055/a-0633-9492
» https://doi.org/10.1055/a-0633-9492
8Bhattacharjee A, Kulkarni VH, Chakraborty M, Habbu PV, Ray A. Ellagic acid restored lead-induced nephrotoxicity by anti-inflammatory, anti-apoptotic and free radical scavenging activities. Heliyon. 2021;7(1):e05921. doi: 10.1016/j.heliyon.2021.e05921
» https://doi.org/10.1016/j.heliyon.2021.e05921
9Tekin GG, Deveci B, Deveci E. Ellagic acid protected the gingival tissue via fibroblast and epidermal growth factors in rats. Acta Cir Bras. 2024;39:e391224. doi: 10.1590/acb391224
» https://doi.org/10.1590/acb391224
10Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci. 2016;73(20):3861–85. doi: 10.1007/s00018-016-2268-0
» https://doi.org/10.1007/s00018-016-2268-0
11Bao P, Kodra A, Tomic-Canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153(2):347–58. doi: 10.1016/j.jss.2008.04.023
» https://doi.org/10.1016/j.jss.2008.04.023
12Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care (New Rochelle). 2014;3(10):647–61. doi: 10.1089/wound.2013.0517
» https://doi.org/10.1089/wound.2013.0517
13Apte RS, Chen DS, Ferrara N. VEGF in signaling and disease: beyond discovery and development. Cell. 2019;176(6):1248–64. doi: 10.1016/j.cell.2019.01.021
» https://doi.org/10.1016/j.cell.2019.01.021
14Nirwana I, Alexandra MF, Nuraida TB, Bermani AT, Shahaniz Y, Rianti D, et al. Synergistic effects of zinc oxide and ellagic acid on macrophage infiltration, angiogenesis, and collagen deposition in excisional wounds healing. J Oral Biol Craniofac Res. 2026;16(2):101398. doi: 10.1016/j.jobcr.2026.01.002
» https://doi.org/10.1016/j.jobcr.2026.01.002
15Lansdown AB, Mirastschijski U, Stubbs N, Scanlon E, Ågren MS. Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound Repair Regen. 2007;15(1):2–16. doi: 10.1111/j.1524-475X.2006.00179.x
» https://doi.org/10.1111/j.1524-475X.2006.00179.x
16Li M, Hou Q, Zhong L, Zhao Y, Fu X. Macrophage related chronic inflammation in non-healing wounds. Front Immunol. 2021;12:681710. doi: 10.3389/fimmu.2021.681710
» https://doi.org/10.3389/fimmu.2021.681710
17Liu YL, Huang HJ, Sheu SY, Lee IJ, Chiang SC, Lin AM, et al. Oral ellagic acid attenuated LPS-induced neuroinflammation in rat brain: MEK1 interaction and M2 microglial polarization. Exp Biol Med (Maywood). 2023;248(7):656–64. doi: 10.1177/15353702231182230
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