Abstract
In our previous work, we have attempted to develop a novel bacterial nanocellulose wound dressing which composed of both polyhexamethylene biguanide (PHMB) as an antimicrobial agent and sericin as an accelerative wound healing component. The loading sequence and concentration of PHMB and sericin were optimized to provide the wound dressing with the most effective antimicrobial activity and enhanced collagen production. In this study, further in vitro, in vivo, and clinical studies of this novel wound dressing were performed to evaluate its safety, efficacy, and applicability. For the in vitro cytotoxic test with L929 mouse fibroblast cells, our novel dressing was not toxic to the cells and also promoted cell migration as good as the commercially available dressing, possibly due to the component of sericin released. When implanted subcutaneously in rats, the lower inflammation response was observed for the novel dressing implanted, comparing to the commercially available dressing. This might be that the antimicrobial PHMB component of the novel dressing played a role to reduce infection and inflammation reaction. The clinical trial patch test was performed on the normal skin of healthy volunteers to evaluate the irritation effect of the dressing. Our novel dressing did not irritate the skin of any volunteers, as characterized by the normal levels of erythema and melanin and the absence of edema, papule, vesicle, and bullae. Then, the novel dressing was applied for the treatment of full-thickness wounds in rats. The wounds treated with our novel dressing showed significantly lower percentage of wound size and higher extent of collagen formation mainly due to the activity of sericin. We concluded that our novel bacterial nanocellulose incorporating PHMB and sericin was a safe and efficient wound dressing material for further investigation in the wound healing efficacy in clinic.
Similar content being viewed by others
References
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):224–233
Aramwit P, Bang N (2014) The characteristics of bacterial nanocellulose gel releasing silk sericin for facial treatment. BMC Biotechnol 14:104
Aramwit P, Bang N, Ratanavaraporn J, Nakpheng T, Srichana T (2014) An anti-cancer cordycepin produced by Cordyceps militaris growing on the dead larva of Bombyx mori Silkworm. J Agr Sci 6(6):41–53
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):1295–1306
Aramwit P, Kanokpanont S, De-Eknamkul W, Srichana T (2009) Monitoring of inflammatory mediators induced by silk sericin. J Biosci Bioeng 107(5):556–561
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):2200–2211
Aramwit P, Sangcakul A (2007) The effects of sericin cream on wound healing in rats. Biosci Biotechnol Biochem 71(10):2473–2477
Chaby G, Viseux V, Poulain JF, De Cagny B, Denoeux JP, Lok C (2005) Topical silver sulfadiazine-induced acute renal failure. Ann Dermatol Venereol 132(11 Pt 1):891–893
Cuttle L, Kempf M, Phillips GE, Mill J, Hayes MT, Fraser JF, Wang XQ, Kimble RM (2006) A porcine deep dermal partial thickness burn model with hypertrophic scarring. Burns 32(7):806–820
Czaja W, Krystynowicz A, Bielecki S, Brown RM Jr (2006) Microbial cellulose—the natural power to heal wounds. Biomaterials 27(2):145–151
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):12, 14–16, 18–20
Gibran NS, Boyce S, Greenhalgh DG (2007) Cutaneous wound healing. J Burn Care Res 28(4):577–579
Hasatsri S, Yamdech R, Chanvorachote P, Aramwit P (2015) Physical and biological assessments of the innovative bilayered wound dressing made of silk and gelatin for clinical applications. J Biomater Appl 29(9):1304–1313
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):534, 536–539
Lin W, Truong N, Grossman WJ, Haribhai D, Williams CB, Wang J, Martin MG, Chatila TA (2005) Allergic dysregulation and hyperimmunoglobulinemia E in Foxp3 mutant mice. J Allergy Clin Immunol 116(5):1106–1115
Loddenkemper C, Schernus M, Noutsias M, Stein H, Thiel E, Nagorsen D (2006) In situ analysis of FOXP3+ regulatory T cells in human colorectal cancer. J Transl Med 4:52
Maenthaisong R, Chaiyakunapruk N, Warnnissorn P, Viyoch J (2009) Cleansing lotion containing tamarind fruit pulp extract. III. Study of lightening efficacy and skin irritation on Asian skin type. ScienceAsia 35:24–30
Moore K, Gray D (2007) Using PHMB antimicrobial to prevent wound infection. Wounds UK 3(2):96–102
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):16–19
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 55:95–104
Nouri-Aria KT (2009) Foxp3 expressing regulatory T-cells in allergic disease. Adv Exp Med Biol 665:180–194
Roth B, Brill FH (2010) Polyhexanide for wound treatment—how it began. Skin Pharmacol Physiol 23(Suppl):4–6
Sakaguchi S, Wing K, Miyara M (2007) Regulatory T cells—a brief history and perspective. Eur J Immunol 37(Suppl 1):S116–S123
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):104–116
Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21:685–711
Sullivan PK, Conner-Kerr TA, Hamilton H, Smith EP, Tefertiller C, Webb A (2004) Assessment of wound bioburden development in a rat acute wound model: quantitative swab versus tissue biopsy. Wounds 16(4):115–123
Takahashi H, Ruiz P, Ricordi C, Delacruz V, Miki A, Mita A, Misawa R, Barker S, Burke GW, Tzakis AG, Ichii H (2012) Quantitative in situ analysis of FoxP3+ T regulatory cells on transplant tissue using laser scanning cytometry. Cell Transplant 21(1):113–125
Tateosian NL, Reiteri RM, Amiano NO, Costa MJ, Villalonga X, Guerrieri D, Maffia PC (2011) Neutrophil elastase treated dendritic cells promote the generation of CD4(+)FOXP3(+) regulatory T cells in vitro. Cell Immunol 269(2):128–134
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):414–419
Vorobjova T, Uibo O, Heilman K, Uibo R (2015) Increased density of tolerogenic dendritic cells in the small bowel mucosa of celiac patients. World J Gastroenterol 21(2):439–452
Wang J, Ioan-Facsinay A, van der Voort EI, Huizinga TW, Toes RE (2007) Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 37(1):129–138
Acknowledgments
The authors gratefully acknowledge all supports from the Faculty of Pharmaceutical Sciences, Chulalongkorn University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Napavichayanun, S., Yamdech, R. & Aramwit, P. 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, 123–132 (2016). https://doi.org/10.1007/s00403-016-1621-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-016-1621-3