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Inflammatory reaction, clinical efficacy, and safety of bacterial cellulose wound dressing containing silk sericin and polyhexamethylene biguanide for wound treatment

  • Supamas Napavichayanun
  • Sumate Ampawong
  • Tavornchai Harnsilpong
  • Apichai Angspatt
  • Pornanong Aramwit
Original Paper
  • 7 Downloads

Abstract

Bacterial cellulose wound dressings containing silk sericin and PHMB (BCSP) were developed in our previous studies. It had good physical properties, efficacy, and safety. For further use as a medical material, this dressing was investigated for its efficacy and safety in split-thickness skin graft (STSG) donor-site wound treatment compared to Bactigras® (control). Moreover, the inflammatory responses to both dressings were also deeply investigated. For in vivo study, expressions of anti-inflammatory cytokines were intensely considered in the tissue interfacing area. The result showed that IL-4 and TGF-β from BCSP-treated tissue had advantages over Bactigras®-treated tissue at 14 and 21 days post-implantation. For clinical study, a single-blinded, randomized controlled study was generated. The half of STSG donor site wound was randomly assigned to cover with BCSP or Bactigras®. Twenty-one patients with 32 STSG donor site wounds were enrolled. The results showed that wound-healing time was not significantly different in both dressings. However, wound quality of BCSP was better than Bactigras® at healing time and after 1 month (p < 0.05). The pain scores of BCSP-treated wound were statistically significant lower than Bactigras®-treated wound (p < 0.05). No sign of infection or adverse event was observed after treatment with both dressings. In conclusion, the inflammation responses of the dressing were clearly clarified. The advantages of BCSP were wound-quality improvement, pain reduction, and infection protection without adverse events. It was fit to be used as the alternative treatment of STSG donor site wound.

Keywords

Bacterial cellulose Dressing Sericin PHMB STSG donor site Treatment 

Notes

Acknowledgements

This research is supported by the 90th Anniversary of Chulalongkorn University, Rachadapisek Sompote Fund to Supamas Napavichayanun.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

(Research involving Human Participants and/or Animals) All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethics Committee of the Faculty of Medicine, Chulalongkorn University (CUACUC 13/57). All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Review Committee for Research Involving Human Research Subjects, Institutional Review Board, Faculty of Medicine, Chulalongkorn University (COA No. 843/2015).

Informed consent

Informed written consent was obtained from all individual participants.

References

  1. 1.
    Alvarez OM, Patel M, Booker J, Markowitz L (2004) Effectiveness of a biocellulose wound dressing for the treatment of chronic venous leg ulcers: results of a single center randomized study involving 24 patients. Wounds 16(7):224–233Google Scholar
  2. 2.
    Aramwit P, Kanokpanont S, De-Eknamkul W, Kamei K, Srichana T (2009) The effect of sericin with variable amino-acid content from different silk strains on the production of collagen and nitric oxide. J Biomater Sci Polym Ed 20(9):1295–1306CrossRefGoogle Scholar
  3. 3.
    Aramwit P, Kanokpanont S, De-Eknamkul W, Srichana T (2009) Monitoring of inflammatory mediators induced by silk sericin. J Biosci Bioeng 107(5):556–561CrossRefGoogle Scholar
  4. 4.
    Aramwit P, Kanokpanont S, Nakpheng T, Srichana T (2010) The effect of sericin from various extraction methods on cell viability and collagen production. Int J Mol Sci 11(5):2200–2211CrossRefGoogle Scholar
  5. 5.
    Aramwit P, Keongamaroon O, Siritientong T, Bang N, Supasyndh O (2012) Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study. BMC Nephrol 13:119–119CrossRefGoogle Scholar
  6. 6.
    Aramwit P, Palapinyo S, Srichana T, Chottanapund S, Muangman P (2013) Silk sericin ameliorates wound healing and its clinical efficacy in burn wounds. Arch Dermatol Res 305(7):585–594CrossRefGoogle Scholar
  7. 7.
    Aramwit P, Sangcakul A (2007) The effects of sericin cream on wound healing in rats. Biosci Biotechnol Biochem 71(10):2473–2477CrossRefGoogle Scholar
  8. 8.
    Aramwit P, Towiwat P, Srichana T (2013) Anti-inflammatory potential of silk sericin. Nat Prod Commun 8(4):501–504PubMedGoogle Scholar
  9. 9.
    Atiyeh BS, El-Musa KA, Dham R (2003) Scar quality and physiologic barrier function restoration after moist and moist-exposed dressings of partial-thickness wounds. Dermatol Surg 29(1):14–20PubMedGoogle Scholar
  10. 10.
    Barnea Y, Amir A, Leshem D, Zaretski A, Weiss J, Shafir R, Gur E (2004) Clinical comparative study of aquacel and paraffin gauze dressing for split-skin donor site treatment. Ann Plast Surg 53(2):132–136CrossRefGoogle Scholar
  11. 11.
    Brandt EB, Sivaprasad U (2011) Th2 Cytokines and atopic dermatitis. J Clin Cell Immunol 2(3):110CrossRefGoogle Scholar
  12. 12.
    Chen L, Arbieva ZH, Guo S, Marucha PT, Mustoe TA, DiPietro LA (2010) Positional differences in the wound transcriptome of skin and oral mucosa. BMC Genom 11:471CrossRefGoogle Scholar
  13. 13.
    Coban YK, Aytekin AH, Tenekeci G (2011) Skin graft harvesting and donor site selection. Skin grafts—indications, applications and current research. InTech.  https://doi.org/10.5772/21957 CrossRefGoogle Scholar
  14. 14.
    Daeschlein G, Assadian O, Bruck JC, Meinl C, Kramer A, Koch S (2007) Feasibility and clinical applicability of polihexanide for treatment of second-degree burn wounds. Skin Pharmacol Physiol 20(6):292–296CrossRefGoogle Scholar
  15. 15.
    Davis EC, Callender VD (2010) Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol 3(7):20–31PubMedPubMedCentralGoogle Scholar
  16. 16.
    Eberlein T, Assadian O (2010) Clinical use of polihexanide on acute and chronic wounds for antisepsis and decontamination. Skin Pharmacol Physiol 23:45–51CrossRefGoogle Scholar
  17. 17.
    Eberlein T, Haemmerle G, Signer M, Gruber Moesenbacher U, Traber J, Mittlboeck M, Abel M, Strohal R (2012) Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds. J Wound Care 21(1):12CrossRefGoogle Scholar
  18. 18.
    Elzinga G, van Doorn J, Wiersema AM, Klicks RJ, Andriessen A, Alblas JG, Spits H, Post A, van Gent M (2011) Clinical evaluation of a PHMB-impregnated biocellulose dressing on paediatric lacerations. J Wound Care 20(6):280–284CrossRefGoogle Scholar
  19. 19.
    Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA (1989) Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci USA 86(10):3803–3807CrossRefGoogle Scholar
  20. 20.
    Hasatsri S, Angspatt A, Aramwit P (2015) Randomized clinical trial of the innovative bilayered wound dressing made of silk and gelatin: safety and efficacy tests using a split-thickness skin graft model. Evid Based Complement Alternat Med 5:8Google Scholar
  21. 21.
    Innes ME, Umraw N, Fish JS, Gomez M, Cartotto RC (2001) The use of silver coated dressings on donor site wounds: a prospective, controlled matched pair study. Burns 27(6):621–627CrossRefGoogle Scholar
  22. 22.
    Kaehn K (2010) Polihexanide: a safe and highly effective biocide. Skin Pharmacol Physiol 23:7–16CrossRefGoogle Scholar
  23. 23.
    Klinkert K, Whelan D, Clover AJP, Leblond AL, Kumar AHS, Caplice NM (2017) Selective M2 macrophage depletion leads to prolonged inflammation in surgical wounds. Eur Surg Res 58(3–4):109–120CrossRefGoogle Scholar
  24. 24.
    Lenselink E, Andriessen A (2011) A cohort study on the efficacy of a polyhexanide-containing biocellulose dressing in the treatment of biofilms in wounds. J Wound Care 20(11):534CrossRefGoogle Scholar
  25. 25.
    McNally AK, Anderson JM (2011) Macrophage fusion and multinucleated giant cells of inflammation. Adv Exp Med Biol 713:97–111CrossRefGoogle Scholar
  26. 26.
    Mia S, Warnecke A, Zhang XM, Malmstrom V, Harris RA (2014) An optimized protocol for human M2 macrophages using M-CSF and IL-4/IL-10/TGF-beta yields a dominant immunosuppressive phenotype. Scand J Immunol 79(5):305–314CrossRefGoogle Scholar
  27. 27.
    Muangman P, Opasanon S, Suwanchot S, Thangthed O (2011) Efficiency of microbial cellulose dressing in partial-thickness burn wounds. J Am Col Certif Wound Spec 3(1):16–19PubMedPubMedCentralGoogle Scholar
  28. 28.
    Muller G, Kramer A (2008) Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. J Antimicrob Chemother 61(6):1281–1287CrossRefGoogle Scholar
  29. 29.
    Napavichayanun S, Amornsudthiwat P, Pienpinijtham P, Aramwit P (2015) Interaction and effectiveness of antimicrobials along with healing-promoting agents in a novel biocellulose wound dressing. Mater Sci Eng C Mater Biol Appl 55:95–104CrossRefGoogle Scholar
  30. 30.
    Napavichayanun S, Yamdech R, Aramwit P (2016) The safety and efficacy of bacterial nanocellulose wound dressing incorporating sericin and polyhexamethylene biguanide: in vitro, in vivo and clinical studies. Arch Dermatol Res 308(2):123–132CrossRefGoogle Scholar
  31. 31.
    Napavichayanun S, Yamdech R, Aramwit P (2018) Development of bacterial cellulose incorporating silk sericin, polyhexamethylene biguanide, and glycerin with enhanced physical properties and antibacterial activities for wound dressing application. Int J Polym Mater Po 67(2):61–67CrossRefGoogle Scholar
  32. 32.
    Oliveira CMBD, Sakata RK, Issy AM, Gerola LR, Salomão R (2011) Cytokines and Pain. Braz J Anesthesiol 61(2):255–265CrossRefGoogle Scholar
  33. 33.
    Padamwar MN, Pawar AP, Daithankar AV, Mahadik KR (2005) Silk sericin as a moisturizer: an in vivo study. J Cosmet Dermatol 4(4):250–257CrossRefGoogle Scholar
  34. 34.
    Pakyari M, Farrokhi A, Maharlooei MK, Ghahary A (2013) Critical role of transforming growth factor beta in different phases of wound healing. Adv Wound Care 2(5):215–224CrossRefGoogle Scholar
  35. 35.
    Roth B, Brill FH (2010) Polihexanide for wound treatment–how it began. Skin Pharmacol Physiol 23:4–6CrossRefGoogle Scholar
  36. 36.
    Salmon-Ehr V, Ramont L, Godeau G, Birembaut P, Guenounou M, Bernard P, Maquart F-X (2000) Implication of interleukin-4 in wound healing. Lab Invest 80:1337CrossRefGoogle Scholar
  37. 37.
    Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA (2009) Anti-inflammatory and pro-inflammatory roles of TGF-beta, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol 9(4):447–453CrossRefGoogle Scholar
  38. 38.
    Siritientong T, Angspatt A, Ratanavaraporn J, Aramwit P (2014) Clinical potential of a silk sericin-releasing bioactive wound dressing for the treatment of split-thickness skin graft donor sites. Pharm Res 31(1):104–116CrossRefGoogle Scholar
  39. 39.
    Terada S, Nishimura T, Sasaki M, Yamada H, Miki M (2002) Sericin, a protein derived from silkworms, accelerates the proliferation of several mammalian cell lines including a hybridoma. Cytotechnology 40(1–3):3–12CrossRefGoogle Scholar
  40. 40.
    Torres F, Commeaux S, Troncoso O (2012) Biocompatibility of Bacterial Cellulose Based Biomaterials. J Funct Biomater 3(4):864–878CrossRefGoogle Scholar
  41. 41.
    Tsubouchi K, Igarashi Y, Takasu Y, Yamada H (2005) Sericin enhances attachment of cultured human skin fibroblasts. Biosci Biotechnol Biochem 69(2):403–405CrossRefGoogle Scholar
  42. 42.
    Velnar T, Bailey T, Smrkolj V (2009) The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 37(5):1528–1542CrossRefGoogle Scholar
  43. 43.
    Verschuren PG, Cardona TD, Nout MJ, De Gooijer KD, Van den Heuvel JC (2000) Location and limitation of cellulose production by Acetobacter xylinum established from oxygen profiles. J Biosci Bioeng 89(5):414–419CrossRefGoogle Scholar
  44. 44.
    Voineskos SH, Ayeni OA, McKnight L, Thoma A (2009) Systematic review of skin graft donor-site dressings. Plast Reconstr Surg 124(1):298–306CrossRefGoogle Scholar
  45. 45.
    Wang W, Huang XR, Li AG, Liu F, Li JH, Truong LD, Wang XJ, Lan HY (2005) Signaling mechanism of TGF-beta1 in prevention of renal inflammation: role of Smad7. J Am Soc Nephrol 16(5):1371–1383CrossRefGoogle Scholar
  46. 46.
    Wang XJ, Han G, Owens P, Siddiqui Y, Li AG (2006) Role of TGF beta-mediated inflammation in cutaneous wound healing. J Investig Dermatol Symp Proc 11(1):112–117CrossRefGoogle Scholar
  47. 47.
    Wiechula R (2003) The use of moist wound-healing dressings in the management of split-thickness skin graft donor sites: a systematic review. Int J Nurs Pract 9(2):S9–S17CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Bioactive Resources for Innovative Clinical Applications Research UnitChulalongkorn UniversityBangkokThailand
  2. 2.Department of Pharmacy Practice, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand
  3. 3.Department of Tropical Pathology, Faculty of Tropical MedicineMahidol UniversityBangkokThailand
  4. 4.Division of Plastic and Reconstructive Surgery, Department of Surgery, Faculty of MedicineChulalongkorn UniversityBangkokThailand

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