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Rakhshan K, Marzban A, Haghighatian Z, Raisi A, Zarei L, Roshani A. Evaluation of Zinc Oxide Nanoparticles Coated with Acetylsalicylate on the Wound Healing Process in Male Rats. pbp 2026; 8
URL: http://pbp.medilam.ac.ir/article-1-326-en.html
URL: http://pbp.medilam.ac.ir/article-1-326-en.html
Kazem Rakhshan1 
, Abdolrazagh Marzban2 , Zahra Haghighatian3 , Abbas Raisi4 , Leila Zarei *5 , Asadollah Roshani6
, Abdolrazagh Marzban2 , Zahra Haghighatian3 , Abbas Raisi4 , Leila Zarei *5 , Asadollah Roshani6
1- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
2- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
3- Department of Pathology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
4- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
5- Palliative Care Research Center, Ur.C., Islamic Azad University, Urmia, Iran ,leilazarei652@yahoo.com
6- Department of Surgery, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
2- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
3- Department of Pathology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
4- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
5- Palliative Care Research Center, Ur.C., Islamic Azad University, Urmia, Iran ,
6- Department of Surgery, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
Abstract: (322 Views)
Objective: Wound healing is a vital physiological process that maintains the skin’s barrier function and prevents infection. The emergence of nanotechnology, particularly metallic nanoparticles, has introduced new strategies to enhance and accelerate wound repair. Among these, zinc oxide nanoparticles coated with acetylsalicylate have attracted attention due to their combined antibacterial and regenerative properties, positioning them as a promising therapeutic option in wound management. This study aimed to evaluate the effects of acetylsalicylate-coated zinc oxide nanoparticles on wound healing in male rats, with an emphasis on histopathological outcomes.
Methods: Wound repair involves a complex interplay of cellular and biochemical events leading to the restoration of tissue integrity. Forty-eight healthy male Wistar rats of uniform weight were randomly assigned to four groups (n=12 each) after standardized wound induction: Group I (control, no treatment), Group II (treated with standard phenytoin ointment), Group III (treated with base ointment), and Group IV (treated with acetylsalicylate-coated zinc oxide nanoparticles). Treatments were applied once daily for seven consecutive days. Histopathological assessments were conducted on days 7, 14, and 21 post-wounding.
Results: Group IV demonstrated significantly improved histopathological indices and accelerated wound healing compared with the other groups (P < 0.05). The findings indicate that acetylsalicylate-coated zinc oxide nanoparticles possess potent anti-inflammatory, antibacterial, and tissue-regenerative effects that substantially enhance wound repair in this animal model. Notably, epidermal and dermal regeneration across different healing phases was markedly improved, underscoring the efficacy of this nanocomposite.
Conclusion: Acetylsalicylate-coated zinc oxide nanoparticles may serve as a novel and effective therapeutic modality for wound management, particularly in infected wounds. Nevertheless, additional preclinical studies and clinical trials are required to confirm these effects and support their translation to human clinical applications.
Methods: Wound repair involves a complex interplay of cellular and biochemical events leading to the restoration of tissue integrity. Forty-eight healthy male Wistar rats of uniform weight were randomly assigned to four groups (n=12 each) after standardized wound induction: Group I (control, no treatment), Group II (treated with standard phenytoin ointment), Group III (treated with base ointment), and Group IV (treated with acetylsalicylate-coated zinc oxide nanoparticles). Treatments were applied once daily for seven consecutive days. Histopathological assessments were conducted on days 7, 14, and 21 post-wounding.
Results: Group IV demonstrated significantly improved histopathological indices and accelerated wound healing compared with the other groups (P < 0.05). The findings indicate that acetylsalicylate-coated zinc oxide nanoparticles possess potent anti-inflammatory, antibacterial, and tissue-regenerative effects that substantially enhance wound repair in this animal model. Notably, epidermal and dermal regeneration across different healing phases was markedly improved, underscoring the efficacy of this nanocomposite.
Conclusion: Acetylsalicylate-coated zinc oxide nanoparticles may serve as a novel and effective therapeutic modality for wound management, particularly in infected wounds. Nevertheless, additional preclinical studies and clinical trials are required to confirm these effects and support their translation to human clinical applications.
Type of Study: Research |
Subject:
Clinical
Received: 2025/04/6 | Accepted: 2025/08/6 | Published: 2025/12/1
Received: 2025/04/6 | Accepted: 2025/08/6 | Published: 2025/12/1
References
1. Wysocki AB. Skin anatomy, physiology, and pathophysiology. Nurs Clin North Am. 1999;34(4):777-97.
2. Hansbrough JF. Current status of skin replacements for coverage of extensive burn wounds. J Trauma Acute Care Surg. 1990;30:155-9.
3. Ben-Bassat H, Chaouat M, Segal N, Zumai E, Wexler M, Eldad A. How long can cryopreserved skin be stored to maintain adequate graft performance? Burns. 2001;27(5):425-31.
4. Gajiwala K, Gajiwala AL. Evaluation of lyophilised, gamma-irradiated amnion as a biological dressing. Cell Tissue Bank. 2004;5:73-80.
5. Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA. 2013;310(14):1462-72.
6. Baker P, Charlton A, Johnston C, Leahy JJ, Lindegaard K, Pisano I, et al. A review of Willow (Salix spp.) as an integrated biorefinery feedstock. Ind Crops Prod. 2022;189:115823.
7. Mathews KA, Binning A. Wound management using honey. Compend Contin Educ Nurs. 2002;24(1):53-9.
8. Oryan A, Alemzadeh E, Tashkhourian J, Ana SFN. Topical delivery of chitosan-capped silver nanoparticles speeds up healing in burn wounds: A preclinical study. Carbohydr Polym. 2018;200:82-92.
9. Colombo M, Carregal-Romero S, Casula MF, Gutiérrez L, Morales MP, Böhm IB, et al. Biological applications of magnetic nanoparticles. Chem Soc Rev. 2012;41(11):4306-34.
10. Kim JH, Hong YC, Uhm HS. Synthesis of oxide nanoparticles via microwave plasma decomposition of initial materials. Surf Coat Technol. 2007;201(9-11):5114-20.
11. Cheraghipour K, Azarhazine M, Zivdari M, Beiranvand M, Shakib P, Rashidipour M, et al. Evaluation of scolicidal potential of salicylate coated zinc nanoparticles against Echinococcus granulosus protoscoleces. Exp Parasitol. 2023;246:108456.
12. Rasmussen K, Rauscher H, Mech A, Sintes JR, Gilliland D, González M, et al. Physico-chemical properties of manufactured nanomaterials–Characterisation and relevant methods. An outlook based on the OECD Testing Programme. Regul Toxicol Pharmacol. 2018;92:8-28.
13. Haase H, Overbeck S, Rink L. Zinc supplementation for the treatment or prevention of disease: current status and future perspectives. Exp Gerontol. 2008;43(5):394-408.
14. Sharma H, Kumar K, Choudhary C, Mishra PK, Vaidya B. Development and characterization of metal oxide nanoparticles for the delivery of anticancer drug. Artif Cells Nanomed Biotechnol. 2016;44(2):672-9.
15. Baker P, Charlton A, Johnston C, Leahy JJ, Lindegaard K, Pisano I, et al. A review of Willow (Salix spp.) as an integrated biorefinery feedstock. Ind Crops Prod. 2022;189:115823.
16. Shara M, Stohs SJ. Efficacy and safety of white willow bark (Salix alba) extracts. Phytother Res. 2015;29(8):1112-6.
17. Li J, Yin Y, Wang L, Liang P, Li M, Liu X, et al. Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety. Molecules. 2016;21(11):1544.
18. Valverde JM, Giménez MJ, Guillen F, Valero D, Martinez-Romero D, Serrano M. Methyl salicylate treatments of sweet cherry trees increase antioxidant systems in fruit at harvest and during storage. Postharvest Biol Technol. 2015;109:106-13.
19. Boucher HW, Corey GR. Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2008;46(Suppl 5):S344-9.
20. Cheraghipour K, Azarhazine M, Zivdari M, Beiranvand M, Shakib P, Rashidipour M, et al. Evaluation of scolicidal potential of salicylate coated zinc nanoparticles against Echinococcus granulosus protoscoleces. Exp Parasitol. 2023;246:108456.
21. Short WD, Olutoye OO, Padon BW, Parikh UM, Colchado D, Vangapandu H, et al. Advances in non-invasive biosensing measures to monitor wound healing progression. Front Bioeng Biotechnol. 2022;10:952198.
22. Bodo M, Settle T, Royal J, Lombardini E, Sawyer E, Rothwell SW. Multimodal noninvasive monitoring of soft tissue wound healing. J Clin Monit Comput. 2013;27(6):677-88.
23. Islam NU, Jalil K, Shahid M, Rauf A, Muhammad N, Khan A, et al. Green synthesis and biological activities of gold nanoparticles functionalized with Salix alba. Arab J Chem. 2019;12(8):2914-25.
24. Golbui Daghdari S, Ahmadi M, Dastmalchi Saei H, Tehrani AAJNJ. The effect of ZnO nanoparticles on bacterial load of experimental infectious wounds contaminated with Staphylococcus aureus in mice. 2017;4(4):232-6.
25. Siddiqi KS, ur Rahman A, Husen A. Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res Lett. 2018;13(1):141.
26. Ebrahimi R, Roudbari H, Parivor K, Badiei. Evaluation of the effects of zinc oxide nanoparticles on burn wounds in female Syrian mice. Q J Med Sci. 2015;25(4):257-62.
27. Abbaszadeh A, Tehmasebi-Foolad A, Rajabzadeh A, Beigi-Brojeni N, Zarei L. Effects of chitosan/nano selenium biofilm on infected wound healing in rats; an experimental study. Bull Emerg Trauma. 2019;7(3):284.
28. Qiu Z, Kwon AH, Kamiyama Y. Effects of plasma fibronectin on the healing of full-thickness skin wounds in streptozotocin-induced diabetic rats. J Surg Res. 2007;138(1):64-70.
29. Yasin H, Mahmud S, Rizwani GH, Perveen R, Abrar H, Fatima K. Effects of aqueous leaves extract of Holoptelea integrifolia (Roxb) Planch on liver and kidney histopathology of albino rats. Pak J Pharm Sci. 2019;32(2).
30. Cheraghipour K, Azarhazine M, Zivdari M, Beiranvand M, Shakib P, Rashidipour M, et al. Evaluation of scolicidal potential of salicylate coated zinc nanoparticles against Echinococcus granulosus protoscoleces. Exp Parasitol. 2023;246:108456.
31. Jain PK, Huang X, El-Sayed IH, El-Sayed MA. Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008;41(12):1578-86.
32. Gamer A, Leibold E, Van Ravenzwaay B. The in vitro absorption of microfine zinc oxide and titanium dioxide through porcine skin. Toxicol In Vitro. 2006;20(3):301-7.
33. Rezaie A, Mohajeri D, Zarkhah A, Nazeri M. Comparative assessment of Matricaria chamomilla and zinc oxide on healing of experimental skin wounds on rats. 2012.
34. Arslan K, Karahan O, Okus A, Unlu Y, Eryilmaz MA, Ay S, et al. Comparison of topical zinc oxide and silver sulfadiazine in burn wounds: an experimental study. Ulus Travma Acil Cerrahi Derg. 2012;18(5):376-83.
35. Li J, Yin Y, Wang L, Liang P, Li M, Liu X, et al. Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety. Molecules. 2016;21(11):1544.
36. Valverde JM, Giménez MJ, Guillen F, Valero D, Martinez-Romero D, Serrano M. Methyl salicylate treatments of sweet cherry trees increase antioxidant systems in fruit at harvest and during storage. Postharvest Biol Technol. 2015;109:106-13.
37. Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007;127(3):514-25.
38. Dorsett-Martin WA. Rat models of skin wound healing: a review. Wound Repair Regen. 2004;12(6):591-9.
39. Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. Skin wound healing: an update on the current knowledge and concepts. Eur Surg Res. 2017;58(1-2):81-94.
40. Rajakumari K. Skin wound healing: an update on the current knowledge and concepts. Res J Pharm Technol. 2019;12(3):1448-52.
41. Ågren MS, Ostenfeld U, Kallehave F, Gong Y, Raffn K, Crawford ME, et al. A randomized, double-blind, placebo-controlled multicenter trial evaluating topical zinc oxide for acute open wounds following pilonidal disease excision. Wound Repair Regen. 2006;14(5):526-35.
42. Bodnar RJ. Epidermal growth factor and epidermal growth factor receptor: the Yin and Yang in the treatment of cutaneous wounds and cancer. Adv Wound Care (New Rochelle). 2013;2(1):24-9.
43. Martin JM, Zenilman JM, Lazarus GS. Molecular microbiology: new dimensions for cutaneous biology and wound healing. J Invest Dermatol. 2010;130(1):38-48.
44. Brigelius-Flohe R, Aumann KD, Blöcker H, Gross G, Kiess M, Klöppel K, et al. Phospholipid-hydroperoxide glutathione peroxidase. Genomic DNA, cDNA, and deduced amino acid sequence. J Biol Chem. 1994;269(10):7342-8.
45. Bucknall T. The effect of local infection upon wound healing: an experimental study. Br J Surg. 1980;67(12):851-5.
46. Agar OT, Dikmen M, Ozturk N, Yilmaz MA, Temel H, Turkmenoglu FP. Comparative studies on phenolic composition, antioxidant, wound healing and cytotoxic activities of selected Achillea L. species growing in Turkey. Molecules. 2015;20(10):17976-8000.
47. Phan TT, Wang L, See P, Grayer RJ, Chan SY, Lee ST. Phenolic compounds of Chromolaena odorata protect cultured skin cells from oxidative damage: implication for cutaneous wound healing. Biol Pharm Bull. 2001;24(12):1373-9.
48. Lodhi S, Singhai AK. Wound healing effect of flavonoid rich fraction and luteolin isolated from Martynia annua Linn. on streptozotocin induced diabetic rats. Asian Pac J Trop Med. 2013;6(4):253-9.
49. Li J, Yin Y, Wang L, Liang P, Li M, Liu X, et al. Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety. Molecules. 2016;21(11):1544.
50. Barui AK, Veeriah V, Mukherjee S, Manna J, Patel AK, Patra S, et al. Zinc oxide nanoflowers make new blood vessels. Nanoscale. 2012;4(24):7861-9.
51. Bartczak D, Muskens OL, Sanchez-Elsner T, Kanaras AG, Millar TM. Manipulation of in vitro angiogenesis using peptide-coated gold nanoparticles. ACS Nano. 2013;7(6):5628-36.
52. Mukherjee S, Sriram P, Barui AK, Nethi SK, Veeriah V, Chatterjee S, et al. Graphene oxides show angiogenic properties. Adv Healthc Mater. 2015;4(11):1722-32.
53. Augustine R, Dominic EA, Reju I, Kaimal B, Kalarikkal N, Thomas S. Electrospun polycaprolactone membranes incorporated with ZnO nanoparticles as skin substitutes with enhanced fibroblast proliferation and wound healing. RSC Adv. 2014;4(47):24777-85.
54. Raghupathi KR, Koodali RT, Manna AC. Size-dependent bacterial growth inhibition and mechanism of antibacterial activity of zinc oxide nanoparticles. Langmuir. 2011;27(7):4020-8.
55. Seil JT, Webster TJ. Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomedicine. 2012:2767-81.
56. Rahimi Kalateh Shah Mohammad G, Homayouni Tabrizi M, Ardalan T, Yadamani S, Safavi E. Green synthesis of zinc oxide nanoparticles and evaluation of anti-angiogenesis, anti-inflammatory and cytotoxicity properties. J Biosci. 2019;44:1-9.
57. Rea S, Giles NL, Webb S, Adcroft KF, Evill LM, Strickland DH, et al. Bone marrow-derived cells in the healing burn wound—more than just inflammation. Burns. 2009;35(3):356-64.
58. Chan B, Leong K. Scaffolding in tissue engineering: general approaches and tissue-specific considerations. Eur Spine J. 2008;17(4):467-79.
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