The effect of combination therapy of ultrasound and Aloe Vera gel containing zinc oxide nanoparticles on skin wound healing in mice Combination therapy and wound healing
Iranian Journal of Pharmaceutical Sciences,
Vol. 22 No. 1 (2026),
26 January 2026
,
Page 476-487
https://doi.org/10.22037/ijps.v22i1.49829
Abstract
Wound healing is an intricate pathway of cellular and biochemical events that restore the architecture of cutaneous and subcutaneous tissue. This study investigates the effects of ultrasound (US) radiation combined with Aloe vera gel containing zinc oxide nanoparticles (ZnO NPs) on wound healing. The study was conducted on male mice, which were divided into five groups: control (A), US-treated (B), US + Aloe vera gel-treated (C), US + ZnO NPs-treated (D), and US + Aloe vera gel containing ZnO NPs-treated (E). After making a surgical wound of 1.5 cm on the back of the mice, the local use of gel and US radiation started promptly and proceeded for 15 days. After 15 days, the animals were euthanized for histological examination. US with ZnO NPs led to a substantial increase in collagen count compared with the control cohort. US with ZnO NPs, as well as US alone, significantly increased epithelial thickness and notably elevated collagen and elastin levels in the tissue. The study suggests that combining US radiation with ZnO NPs may significantly increase collagen and elastin levels in the skin's connective tissue and enhance epithelial thickness during wound healing in mice. Improved skin structure can help prevent wound infections by reducing the risk of microbial colonization and promoting faster recovery.
- Wound
- Zinc Oxide Nanoparticle
- Ultrasound Waves
- Aloe Vera
How to Cite
References
1. Tottoli, E.M., et al., Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics, 2020. 12(8): p. 735.
2. Dai, C., S. Shih, and A. Khachemoune, Skin substitutes for acute and chronic wound healing: an updated review. Journal of Dermatological Treatment, 2020. 31(6): p. 639-648.
3. Dixon, D. and M. Edmonds, Managing diabetic foot ulcers: pharmacotherapy for wound healing. Drugs, 2021. 81(1): p. 29-56.
4. Levoux, J., et al., Platelets facilitate the wound-healing capability of mesenchymal stem cells by mitochondrial transfer and metabolic reprogramming. Cell metabolism, 2021. 33(2): p. 283-299. e9.
5. Komi, D.E.A., K. Khomtchouk, and P.L. Santa Maria, A review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clinical reviews in allergy & immunology, 2020. 58: p. 298-312.
6. Masson‐Meyers, D.S., et al., Experimental models and methods for cutaneous wound healing assessment. International journal of experimental pathology, 2020. 101(1-2): p. 21-37.
7. Sajadimajd, S., et al., Herbal nano-ointment containing encapsulated polysaccharide in repairing of superficial ulcers. Nanomedicine Journal, 2024. 11(1).
8. Najafpour, F., et al., Evaluation of wound healing effect of Solanum nigrum L. leaf extract-loaded sodium alginate nanoparticles embedded in chitosan hydrogel, In vivo study. vivo study. Nanomed J, 2022. 9(1): p. 10.22038.
9. Menazea, A. and M. Ahmed, Wound healing activity of Chitosan/Polyvinyl Alcohol embedded by gold nanoparticles prepared by nanosecond laser ablation. Journal of Molecular Structure, 2020. 1217: p. 128401.
10. Ebrahiminia, A., et al., The combination effect of ultrasound and laser therapy on wound healing in diabetic rat model: histological and biomechanical evaluations. International Journal of Diabetes in Developing Countries, 2023. 43(6): p. 1015-1021.
11. Przystupski, D. and M. Ussowicz, Landscape of cellular bioeffects triggered by ultrasound-induced sonoporation. International journal of molecular sciences, 2022. 23(19): p. 11222.
12. Shi, X., et al., Ultrasound-activable piezoelectric membranes for accelerating wound healing. Biomaterials Science, 2022. 10(3): p. 692-701.
13. de Oliveira Perrucini, P.D., et al., Anti-inflammatory and healing effects of pulsed ultrasound therapy on fibroblasts. American journal of physical medicine & rehabilitation, 2020. 99(1): p. 19-25.
14. Li, Y., et al., Effects of Low‐Intensity Pulsed Ultrasound in Tendon Injuries. Journal of Ultrasound in Medicine, 2023. 42(9): p. 1923-1939.
15. Dam, P., et al., Wound healing strategies based on nanoparticles incorporated in hydrogel wound patches. RSC advances, 2023. 13(31): p. 21345-21364.
16. Gültekin, H.E., et al., Advancements and applications of upconversion nanoparticles in wound dressings. Materials Horizons, 2024.
17. Lansdown, A.B., et al., Zinc in wound healing: theoretical, experimental, and clinical aspects. Wound repair and regeneration, 2007. 15(1): p. 2-16.
18. Blinov, A.V., et al., Synthesis and characterization of zinc oxide nanoparticles stabilized with biopolymers for application in wound-healing mixed gels. Gels, 2023. 9(1): p. 57.
19. de Moura, F.B.R., et al., Antioxidant, anti-inflammatory, and wound healing effects of topical silver-doped zinc oxide and silver oxide nanocomposites. International Journal of Pharmaceutics, 2022. 617: p. 121620.
20. Kachare, K., et al., Bio-mediated synthesized zinc oxide coated on cotton fabric for antibacterial and wound healing application. Surface and Coatings Technology, 2024: p. 131171.
21. Oryan, A., et al., Topical Application of Aloe vera Accelerated Wound Healing, Modeling, and Remodeling: An Experimental Study. Annals of Plastic Surgery, 2016. 77(1): p. 37-46.
22. Meza-Valle, K.Z., et al., Characterization and topical study of Aloe vera hydrogel on wound-healing process. Polymers, 2021. 13(22): p. 3958.
23. Hanifa, D., A. Armenia, and A. Djamaan, Preparation and characterization of silver nanoparticles using surian (Toona sinensis) leaf extract and the wound healing efficacy in mice. Nanomedicine Journal, 2024. 11(1).
24. Riaz, S., et al., Chemical characteristics and therapeutic potentials of Aloe vera. RADS Journal of Biological Research & Applied Sciences, 2021. 12(2): p. 160-166.
25. Liang, J., et al., Aloe vera: a medicinal plant used in skin wound healing. Tissue Engineering Part B: Reviews, 2021. 27(5): p. 455-474.
26. Bialik-Wąs, K. and K. Pielichowski, Bio-hybrid acrylic hydrogels containing metronidazole–loaded poly (acrylic acid-co-methyl methacrylate) nanoparticles and Aloe vera as natural healing agent. International Journal of Polymeric Materials and Polymeric Biomaterials, 2019.
27. Wei, Q., et al., Preparation, characterization and application of functional polyethersulfone membranes blended with poly (acrylic acid) gels. Journal of Membrane Science, 2009. 337(1-2): p. 266-273.
28. Serinçay, H., et al., PVA/PAA-based antibacterial wound dressing material with aloe vera. Polymer-Plastics Technology and Engineering, 2013. 52(13): p. 1308-1315.
29. Gergye, C.H., et al., A comparison of ketamine or etomidate combined with xylazine for intraperitoneal anesthesia in four mouse strains. Journal of the American Association for Laboratory Animal Science, 2020. 59(5): p. 519-530.
30. Rezvanipour, M., et al., The effect of mummy on some indices of wound healing in mice. Journal of Kerman University of Medical Sciences, 2007. 14(2): p. 267-277.
31. Kostić, A., et al., Comparison of the swelling kinetics of a partially neutralized poly (acrylic acid) hydrogel in distilled water and physiological solution. Journal of the Serbian Chemical Society, 2007. 72(11): p. 1139-1153.
32. Tamburic, S. and D.Q. Craig, An investigation into the rheological, dielectric and mucoadhesive properties of poly (acrylic acid) gel systems. Journal of Controlled Release, 1995. 37(1-2): p. 59-68.
33. Batool, M., et al., Adsorption, antimicrobial and wound healing activities of biosynthesised zinc oxide nanoparticles. Chemical Papers, 2021. 75: p. 893-907.
34. Osumi, K., et al., Acceleration of wound healing by ultrasound activation of TiO2 in Escherichia coli‐infected wounds in mice. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2017. 105(8): p. 2344-2351.
35. Lyu, W., et al., Flexible ultrasonic patch for accelerating chronic wound healing. Advanced Healthcare Materials, 2021. 10(19): p. 2100785.
36. Radhika, B., et al., Comparative evaluation of thermal impact of 980nm diode laser on soft tissue using irrigation and non-irrigation systems: A histomorphometric study. Journal of Indian Society of Periodontology, 2024. 28(1): p. 91-98.
37. Vander Horst, M.A., et al., Time-and dose-dependent effects of pulsed ultrasound on dermal repair in diabetic mice. Ultrasound in medicine & biology, 2021. 47(4): p. 1054-1066.
38. Shindo, T. and H. Shimokawa, Therapeutic angiogenesis with sound waves. Annals of Vascular Diseases, 2020. 13(2): p. 116-125.
39. Kong, Y., et al., Wireless localized electrical stimulation generated by an ultrasound‐driven piezoelectric discharge regulates proinflammatory macrophage polarization. Advanced Science, 2021. 8(13): p. 2100962.
40. Goshchynsky, V., et al., Radiofrequency ablation of varicose veins in combination with ultrasonic-assisted wound debridement and platelet-rich plasma as well as platelet-rich fibrin technologies in treatment of lower extremity venous ulcers in office-based surgery. Pan African Medical Journal, 2022. 42(1).
41. Fernández-Guarino, M., et al., The role of physical therapies in wound healing and assisted scarring. International Journal of Molecular Sciences, 2023. 24(8): p. 7487.
42. Weng, Z., et al., Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications. Biomaterials Science, 2023. 11(1): p. 76-95.
43. Rao, K.M., et al., Hemostatic, biocompatible, and antibacterial non-animal fungal mushroom-based carboxymethyl chitosan-ZnO nanocomposite for wound-healing applications. International journal of biological macromolecules, 2020. 155: p. 71-80.
44. Oliveira, A., et al., Therapeutic advances in wound healing. Journal of Dermatological Treatment, 2022. 33(1): p. 2-22.
45. Ahmadi, M. and M. Adibhesami, The effect of silver nanoparticles on wounds contaminated with Pseudomonas aeruginosa in mice: an experimental study. Iranian journal of pharmaceutical research: IJPR, 2017. 16(2): p. 661.
46. Atik, N., M.A.R. Sururi, and R.A. Kartiwa, Comparison of TGF-β1 in corneal laceration with or without Aloe vera gel treatment. Journal of Advanced Pharmacy Education and Research, 2021. 11(1-2021): p. 120-124.
47. Elbialy, Z.I., et al., Healing potential of Spirulina platensis for skin wounds by modulating bFGF, VEGF, TGF-ß1 and α-SMA genes expression targeting angiogenesis and scar tissue formation in the rat model. Biomed Pharmacother, 2021. 137(111349): p. 10.1016.
48. Jamil, M., et al., Review Effect of Aloe vera on Wound Healing: Review: Effect of Aloe vera on Wound Healing. Biological Sciences-PJSIR, 2020. 63(1): p. 48-61.
49. Verma, R., et al., A review of wound healing activity on different wound models. Journal of Applied Pharmaceutical Research, 2019. 7(1): p. 01-07.
- Abstract Viewed: 13 times
- IJPS_Volume22_Issue1_Pages476-487 Downloaded: 3 times