Sliver nanoparticles accelerate skin wound healing in mice (Mus musculus) through suppression of innate immune system

Authors

1 Research Institute of Biotechnology, Shahrekord University, Iran

2 Department of Biology, Shahrekord University, Iran

3 Department of Genetics, Shahrekord University, Iran

4 Deptarment of Biology, Islamic Azad University of Shahrekord, Iran

Abstract

Objective(s):
This study aimed to find the effects of silver nanoparticles (Ag-NPs) (40 nm) on skin wound healing in mice Mus musculus when innate immune system has been suppressed.
Materials and Methods:
A group of 50 BALB/c mice of about 8 weeks (weighting 24.2±3.0 g) were randomly divided into two groups: Ag-NPs and control group, each with 25 mice. Once a day at the same time, a volume of 50 microliters from the nanosilver solution (10ppm) was applied to the wound bed in the Ag-NPs group while in the untreated (control) group no nanosilver solution was used but the wound area was washed by a physiological solution. The experiment lasted for 14. Transforming growth factor beta (TGF-β), complement component C3, and two other immune system factors involving in inflammation, namely C-reactive protein (CRP) and rheumatoid factor (RF) in sera of both groups were assessed and then confirmed by complement CH50 level of the blood.
Results:
The results show that wound healing is a complex process involving coordinated interactions between diverse immunological and biological systems and that Ag-NPs significantly accelerated wound healing and reduce scar appearance through suppression of immune system as indicated by decreasing levels of all inflammatory factors measured in this study.
Conclusion:
Exposure of mice to Ag-NPs can result in significant changes in innate immune function at the molecular levels. The study improves our understanding of nanoparticle interaction with components of the immune system and suggests that Ag-NPs have strong anti-inflammatory effects on skin wound healing and reduce scarring.

Keywords


1. Chen X, Schluesener HJ. Nanosilver: a nanoproduct in medical application. Toxicol Lett. 2008; 176: 1–12.
2. Mei N, Zhang YB, Chen Y, Guo XQ, Ding W., Ali SF, et al. Silver nanoparticle-induced mutations and oxidative stress in mouse lymphoma cells. Environ Mol Mutagen. 2012; 53: 409-419.
3. Nadworny PL, Wang J, Tredget EE, Burrell RE. Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Nanomed. 2008; 4: 241–251.
4. Sibbald, RG, Contreras-Ruiz, J, Coutts P, Fierheller M, Rothman A, Woo K. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Ad Skin Wound Care. 2007; 20: 549–558.
5. Tian J, Wong KK, Ho CM, Lok CN, Yu, WY, Che CM, et al. Topical delivery of silver nanoparticles promotes wound healing. Chem Med Chem 2007; 2: 129–136.
6. Wright JB, Lam K, Buret AG, Olson, ME, Burrell RE. Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing. Wound Rep Regen. 2002; 10: 141–151.
7. Huang Y, Li X, Liao Z, Zhang G, Liu Q, Tang J, et al. A randomized comparative trial between Acticoat and SD-Ag in the treatment of residual burn wounds, including safety analysis. Burns 2007; 33: 161-166.
8. Hendi A. Silver nanoparticles mediate differential responses in some of liver and kidney functions during skin wound healing. J King Saud Uni. 2011; 23: 47-52.
9. Atiyeh BS, Costagliola M, Hayek SN, Dibo SA. Effect of silver on burn wound infection control and healing: Review of the literature. Burns 2007; 33: 139: 148.
10. Cordeiro MF. Beyond mitomycin: TGF- β and wound healing. Prog. Retin. Eye Res. 2002; 21: 75–89.
11. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003; 83: 835–870.
12. Faler BJ, Macsata RA, Plummer D, Mishra L, Sidawy AN. Transforming growth factor-beta and wound healing. Perspect Vasc Surg Endovasc Ther. 2006; 18: 55–62.
13. Bonaparte BS, Hair PS, Banthia D, Marshall DM, Krishna NK. Human astrovirus coat protein inhibits serum complement activation via C1, the first component of the classical pathway. J Virol. 2008;82: 817-827.
14. RAS; Rheumatoid Arthritis Symptoms". Retrieved 2011.
15. Karodi R, Jadhav M, Rub R, Bafna A. Evaluation of the wound healing activity of a crude extract of Rubia cordifolia L. (Indian madder) in mice. Inter J Appl Res Nat Prod. 2009; 2: 12-18
16. Booth NA, Campbell RD, Fothergill JE. The purification and characterization of bovine C4, the fourth component of complement. Biochem J. 1979; 177: 959–965.
17. Goodman G. "Postacne scarring: A review of its pathophysiology and treatment". Dermatologic surgery: official publication for American Society for Dermatologic Surgery. 2000; 26 (9): 857–871.
18. Zolnik BS, Gonzalez-Fernandez A, Sadrieh N, Dobrovolskaia MA. Minireview: Nanoparticles and the Immune System. Endocrinol. 2010;151: 458– 465.
19. Faunce T, Watal A. Nanosilver and global public health: international regulatory issues. Nanomed. 2010; 5: 617–632.
20. Lara HH, Garza-Treviño EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnol. 2011; 9: 1-8.
21. Danilczuk M, Lund A, Sadlo J, Yamada H, Michalik J. Conduction electron spin resonance of small silver particles. Spectrochim Acta A Mol Biomol Spectrosc. 2006; 63: 189-191.
22. Martin P. Wound healing–aiming for perfect skin regeneration. Science 1997; 276:75–81.
23. Chaloupka K, Malam Y, Seifalian AM. Nanosilver as a new generation of nanoproduct in biomedical applications. Trends Biotechnol. 2010; 28: 580-588. 
24. Chanan-Khan A, Szebeni J, Savay S, Liebes L, Rafique NM, Alving CR, et al. Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Ann Oncol. 2003; 14: 1430–1437.
25. Szebeni J. Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. Toxicol. 2005; 216: 106–121.
26. Szebeni. J, Alving CR, Rosivall L, Bunger R, Baranyi L, Bedocs P, et al. 2007. Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles. J Liposome Res. 2007;17: 107–117.
27. Wright BI, Lam K, Buret AG. Early healing events in a porcine model of contaminated wounds: Effect of nanosilver in MMP’s cell apoptosis and healing, J Dermatol. 1991; 124: 519–526.
28. Frank S, Madlener M, Werner S. Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing. J Biol Chem. 1996; 271: 10188–10193.
29. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, et al. TGF-beta receptor-mediated signalling through Smad2, Smad3, and Smad4. EMBO J. 1997; 16: 5353–5362.
30. Lambris JD. The multifunctional role of C3, the third component of complement. Immunol Today. 1998; 9: 387- 393.
31. Barbul A, Shawe T, Rotter SM. Wound healing in nude mice: a study on the regulatory role of lymphocytes fibroplasia. Surgery 1989; 105: 764-769.