Document Type : Original Article

Authors

1 Department of Clinical Studies, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

2 Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

Abstract

Treatment of infected burn wounds remains a challenge in burn units. Silver-sulfadiazine (SSD) is the most commonly used topical antimicrobial agent in managing these wounds. We aimed to accelerate the healing of burn wounds by combined application of ovine acellular peritoneal matrix (OAPM), honey (H), and ovine fetal skin extract (OFSE). Sixty-four standardized burn wounds were created on the dorsum of 16 rats and were subsequently inoculated with Staphyloccocus aureus and Pseudomonas aeruginosa. After 48 hr, the wounds were surgically debrided and received either physiologic saline (control group) or SSD, OAPM+SSD, OAPM+H+SSD, OAPM+H+OFSE+SSD. The healing wounds were evaluated for size, bacterial counts, histopathology, and biomechanical properties on days 3, 7, 14, 21, and 28 after surgery. All treatments had effectively reduced the level of S. aureus and P. aeruginosa on wounds compared to the control group by day 3 and 7. The wounds treated with combined application of OAPM+H+OFSE+SSD demonstrated considerable inflammation reduction, fibroplasia, complete re-epithelialization, and wound contraction together with significantly lesser scar tissue formation. Treatment with OAPM+H+OFSE+SSD showed superior biomechanical properties of the healing wounds. The findings suggested that the synergistic effect of dressing the wounds with OAPM, H, and OFSE was a very effective approach in accelerating the healing process of the experimentally induced infected full-thickness burn wounds in rats.

Keywords

  1. Atalay S, Coruh A, Deniz K. Stromal vascular fraction improves deep partial thickness burn wound healing. Burns 2014;40(7):1375-1383.
  2. Tsai DM, Tracy LE, Lee CCY, et al. Full‐thickness porcine burns infected with Staphylococcus aureus or Pseudomonas aeruginosa can be effectively treated with topical antibiotics. Wound Repair Regen 2016;24(2):356-365.
  3. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Microbiol Rev 2001;14(2): 244-269.
  4. Alp E, Coruh A, Gunay GK, et al. Risk factors for nosocomial infection and mortality in burn patients: 10 years of experience at a university hospital. J Burn Care Res 2012;33(3):379-385.
  5. Church D, Elsayed S, Reid O, et al. Burn wound infections. Clin Microbiol Rev. 2006;19(2):403-434.
  6. Gallagher JJ, Williams-Bouyer N, Villarreal C, et al. Treatment of infection in burns: Total Burn Care. Philadelphia, USA: Elsevier 2007:136-176.
  7. Tiwari VK. Burn wound: How it differs from other wounds? Indian J Plast Surg 2012;45(2):364-373.
  8. Muller MJ, Hollyoak MA, Moaveni Z, et al. Retardation of wound healing by silver sulfadiazine is reversed by Aloe vera and nystatin. Burns 2003;29(8):834-836.
  9. Shahzad MN, Ahmed N. Effectiveness of Aloe Vera gel compared with 1% silver sulphadiazine cream as burn wound dressing in second degree burns. J Pak Med Assoc 2013;63(2):225-230.
  10. Chen X, Shi Y, Shu B, et al. The effect of porcine ADM to improve the burn wound healing. Int J Clin Exp Pathol 2013;6(11):2280-2291.
  11. Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res 2012;49(1):35-43.
  12. Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 2009;17(2):153-162.
  13. Zhong S, Zhang YZ, Lim CT. Tissue scaffolds for skin wound healing and dermal reconstruction. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2010;2(5): 510-525.
  14. Chen RN, Ho HO, Tsai YT, et al. Process development of an acellular dermal matrix (ADM) for biomedical applications. Biomaterials 2004;25(13):2679-2686.
  15. Shukla AK, Dey N, Nandi P et al. Acellular dermis as a dermal matrix of tissue engineered skin substitute for burns treatment. Ann Public Health Res 2015;2(3): 1023. 1-17.
  16. Wu Z, Fan L, Xu B, et al. Use of decellularized scaffolds combined with hyaluronic acid and basic fibroblast growth factor for skin tissue engineering. Tissue Eng Part A 2015;21(1-2):390-402.
  17. Meimandi-Parizi A, Oryan A, Moshiri A. Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study. PLoS ONE 2013;8(9):e73016. doi:10.1371/journal.pone.0073016.
  18. Rizzi SC, Upton Z, Bott K, et al. Recent advances in dermal wound healing: biomedical device approaches. Expert Rev Med Devices 2010;7(1):143-154.
  19. Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials 2011;32(12):3233-3243.
  20. Hasan A, Kumar N, Gopinathan A, et al. Bovine reticulum derived extracellular matrix (b-REM) for reconstruction of full thickness skin wounds in rats. Wound Medicine 2016;12:19-31.
  21. Headon H, Kasem A, Manson A, et al. Clinical outcome and patient satisfaction with the use of bovine-derived acellular dermal matrix (SurgiMendTM) in implant based immediate reconstruction following skin sparing mastectomy: A prospective observational study in a single centre. Surg Oncol 2016;25(2):104-110.
  22. Sahin I, Ozturk S, Deveci M, et al. Experimental assessment of the neo-vascularisation of acellular dermal matrix in the wound bed pretreated with mesenchymal stem cell under subatmospheric pressure. J Plast Reconstr Aesthet Surg 2014; 67(1):107-114.
  23. Salzberg CA, Dunavant C, Nocera N. Immediate breast reconstruction using porcine acellular dermal matrix (Strattice™): Long-term outcomes and complications. J Plast Reconstr Aesthet Surg 2013;66(3):323-328.
  24. Al-Waili N, Salom K, Al-Ghamdi AA. Honey for wound healing, ulcers, and burns; data supporting its use in clinical practice. Sci World J 2011;11:766-787.
  25. Oryan A, Zaker S. Effects of topical application of honey on cutaneous wound healing in rabbits. J Vet Med 1998;45(1‐10):181-188.
  26. Oryan A, Alemzadeh E, Moshiri A. Biological properties and therapeutic activities of honey in wound healing: a narrative review and meta-analysis. J Tissue Viability 2016;25(2):98-118.
  27. Mogoşanu GD, Grumezescu AM. Natural and synthetic polymers for wounds and burns dressing. Int J Pharm 2014;463(2):127-136.
  28. Aziz Z, Hassan BAR. The effects of honey compared to silver sulfadiazine for the treatment of burns: A systematic review of randomized controlled trials. Burns 2017;43(1):50-57.
  29. Cooper RA, Halas E, Molan PC. The efficacy of honey in inhibiting strains of Pseudomonas aeruginosa from infected burns. J Burn Care Rehabil 2002;23(6):366-370.
  30. Cooper RA, Molan PC, Harding KG. Antibacterial activity of honey against strains of Staphylococcus aureus from infected wounds. J R Soc Med 1999;92(6):283-285.
  31. Mohamed SH, Attia GM. A comparison between the effects of topical application of honey and that of amino acids on improving wound healing in aged rats: A histological and immunohistochemical study. Egypt J Histol 2013;36(2):354-564.
  32. Lapp A, Furrer P, Ramelet AA, et al. Cellular derivatives and efficacy in wound and scar manage-ment. J Chem Dermatol Sci Appl 2013;03(01):36-45.
  33. Leung A, Crombleholme TM, Keswani SG. Fetal wound healing: implications for minimal scar formation. Curr Opin Pediatr 2012;24(3):371-378.
  34. Dublet B, van der Rest M. Type XIV collagen, a new homotrimeric molecule extracted from fetal bovine skin and tendon, with a triple helical disulfide-bonded domain homologous to type IX and type XII collagens. J Biol Chem 1991;266(11):6853-6858.
  35. Habuchi H, Kimata K, Suzuki S. Changes in proteo glycan composition during development of rat skin. The occurrence in fetal skin of a chondroitin sulfate proteoglycan with high turnover rate. J Biol Chem 1986;261(3):1031-1040.
  36. Hohlfeld J, De Buys Roessingh AS, Hirt-Burri N, et al. Tissue engineered fetal skin constructs for paediatric burns. Lancet 2005;366(9488):840-842.
  37. De Buys Roessingh AS, Hohlfeld J, Scaletta C et al. Development, characterization, and use of a fetal skin cell bank for tissue engineering in wound healing. Cell Transplant 2006;15(8-9):823-834.
  38. Ramelet AA, Hirt-Burri N, Raffoul W, et al. Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells. Exp Gerontol 2009;44(3):208-218.
  39. Quintin A, Hirt-Burri N, Scaletta C, et al. Consistency and safety of cell banks for research and clinical use: preliminary analysis of fetal skin banks. Cell Transplant 2007;16(7):675-684.
  40. Skehel JM. Preparation of extracts from animal tissues. In: Cutler P (Ed). Protein purification protocols. California, USA: Springer 2004; 15-20.
  41. Cai EZ, Ang CH, Raju A, et al. Creation of consistent burn wounds: a rat model. Arch Plast Surg 2014;41(4):317-324.
  42. Oryan A, Jalili M, Kamali A, et al. The concurrent use of probiotic microorganism and collagen hydrogel/ scaffold enhances burn wound healing: An in vivo evaluation. Burns 2018; 44(7):1775-1786
  43. Edwards C, Marks R. Evaluation of biomechanical properties of human skin. Clin Dermatol 1995;13(4):375-380.
  44. Lu WW, Ip WY, Jing WM, et al. Biomechanical properties of thin skin flap after basic fibroblast growth factor (bFGF) administration. Br J Plast Surg 2000;53(3):225-229.
  45. Atiyeh BS, Costagliola M, Hayek SN, et al. Effect of silver on burn wound infection control and healing: review of the literature. Burns 2007;33(2):139-148.
  46. Vingsbo Lundberg C, Frimodt-Møller N. Efficacy of topical and systemic antibiotic treatment of meticillin-resistant Staphylococcus aureus in a murine superficial skin wound infection model. Int J Antimicrob Agents 2013;42(3):272-275.
  47. Clark RAF, Ghosh K, Tonnesen MG. Tissue engineering for cutaneous wounds. J Invest Dermatol 2007;127(5): 1018-1029.
  48. Salzberg CA, Ashikari AY, Berry C, et al. Acellular dermal matrix-assisted direct-to-implant breast reconstruction and capsular contracture: a 13-year experience. Plast Reconstr Surg 2016;138(2):329-337.