In vivo evaluation of bacterial cellulose/acrylic acid wound dressing hydrogel containing keratinocytes and fibroblasts for burn wounds
The healing of wounds, including those from burns, currently exerts a burden on healthcare systems worldwide. Hydrogels are widely used as wound dressings and in the field of tissue engineering. The popularity of bacterial cellulose-based hydrogels has increased owing to their biocompatibility. Previous study demonstrated that bacterial cellulose/acrylic acid (BC/AA) hydrogel increased the healing rate of burn wound. This in vivo study using athymic mice has extended the use of BC/AA hydrogel by the addition of human epidermal keratinocytes and human dermal fibroblasts. The results showed that hydrogel loaded with cells produces the greatest acceleration on burn wound healing, followed by treatment with hydrogel alone, compared with the untreated group. The percentage wound reduction on day 13 in the mice treated with hydrogel loaded with cells (77.34 ± 6.21%) was significantly higher than that in the control-treated mice (64.79 ± 6.84%). Histological analysis, the expression of collagen type I via immunohistochemistry, and transmission electron microscopy indicated a greater deposition of collagen in the mice treated with hydrogel loaded with cells than in the mice administered other treatments. Therefore, the BC/AA hydrogel has promising application as a wound dressing and a cell carrier.
KeywordsCell carrier Tissue regeneration Skin injury Wound healing
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval and consent to participate
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
All institutional and national guidelines for the care and use of laboratory animals were followed.
- 7.Wojtowicz AM, Oliveira S, Carlson MW, Zawadzka A, Rousseau CF, Baksh D. The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing. Wound Repair Regen. 2014;22(2):246–55. https://doi.org/10.1111/wrr.12154.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Hassan A, Halim AS, Hilmi ABMA. Bilayer engineered skin substitute for wound repair in an irradiation-impeded healing model on rat. Adv Wound Care (New Rochelle). 2015;4(5):312–20. https://doi.org/10.1089/wound.2014.0551
- 10.Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;54(1):3–12. https://doi.org/10.1016/S0169-409X(01)00239-3
- 12.Balakrishnan B, Mohanty M, Umashankar PR, Jayakrishnan A. Evaluation of an in situ forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials. 2005;26(32):6335–42. https://doi.org/10.1016/j.biomaterials.2005.04.012.CrossRefPubMedGoogle Scholar
- 14.Sun G, Zhang X, Shen Y, Sebastian R, Dickinson LE, Talbot KF, et al. Dextran hydrogel scaffolds enhance angiogenic responses and promote complete skin regeneration during burn wound healing. Proc Natl Acad Sci. 2011;108(52):20976–81. https://doi.org/10.1073/pnas.1115973108.CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Varkey M, Ding J, Tredget EE, Wound-Healing-Research-Group. The effect of keratinocytes on the biomechanical characteristics and pore microstructure of tissue engineered skin using deep dermal fibroblasts. Biomaterials. 2014;35(36):9591–8. https://doi.org/10.1016/j.biomaterials.2014.07.048.CrossRefPubMedGoogle Scholar
- 18.Wippermann J, Schumann D, Klemm D, Kosmehl H, Salehi-Gelani S, Wahlers T. Preliminary results of small arterial substitute performed with a new cylindrical biomaterial composed of bacterial cellulose. Eur J Vasc Endovasc. 2009;37(5):592–6. https://doi.org/10.1016/j.ejvs.2009.01.007.CrossRefGoogle Scholar
- 19.Czaja W, Krystynowicz A, Bielecki S, Brown RM. Microbial cellulose—the natural power to heal wounds. Biomaterials. 2006;27(2):145–51. https://doi.org/10.1016/j.biomaterials.2005.07.035.CrossRefPubMedGoogle Scholar
- 20.Kwak MH, Kim JE, Go J, Koh EK, Song SH, Son HJ, et al. Bacterial cellulose membrane produced by Acetobacter sp. A10 for burn wound dressing applications. Carbohydr Polym. 2015;122:387–98. https://doi.org/10.1016/j.carbpol.2014.10.049
- 21.Muangman P, Opasanon S, Suwanchot S, Thangthed O. Efficiency of microbial cellulose dressing in partial-thickness burn wounds. J Am Coll Certif Wound Spec. 2011;3(1):16–9. https://doi.org/10.1016/j.jcws.2011.04.001
- 24.Mohamad N, Buang F, Mat Lazim A, Ahmad N, Martin C, Mohd Amin MC. Characterization and biocompatibility evaluation of bacterial cellulose-based wound dressing hydrogel: effect of electron beam irradiation doses and concentration of acrylic acid. J Biomed Mater Res B Appl Biomater. 2017;105(8):2553–64. https://doi.org/10.1002/jbm.b.33776.CrossRefPubMedGoogle Scholar
- 25.Seet WT, Manira M, Khairul Anuar K, Chua KH, Ahmad Irfan AW, Ng MH, et al. Shelf-life evaluation of bilayered human skin equivalent, MyDerm™. PLoS One. 2012;7:e40978. https://doi.org/10.1371/journal.pone.0040978
- 26.Loo Y, Wong YC, Cai EZ, Ang CH, Raju A, Lakshmanan A, et al. Ultrashort peptide nanofibrous hydrogels for the acceleration of healing of burn wounds. Biomaterials. 2014;35:1–10. https://doi.org/10.1016/j.biomaterials.2014.02.047
- 27.Busra MF, Chowdhury SR, Ismail F, Saim A, Idrus RH. Tissue-engineered skin substitute enhances wound healing after radiation therapy. Adv Skin Wound Care. 2016;29(3):120–9. https://doi.org/10.1097/01.ASW.0000480556.78111.e4.CrossRefPubMedGoogle Scholar
- 28.Idrus RB, Rameli MA, Low KC, Law JX, Chua KH, Latiff MB, et al. Full-thickness skin wound healing using autologous keratinocytes and dermal fibroblasts with fibrin: bilayered versus single-layered substitute. Adv Skin Wound Care. 2014;27(4):171–80. https://doi.org/10.1097/01.ASW.0000445199.26874.9d.CrossRefPubMedGoogle Scholar
- 29.Rogers AA, Walmsley RS, Rippon MG, Bowler PG. Adsorption of serum-derived proteins by primary dressings: implications for dressing adhesion to wounds. J Wound Care. 2016;8:403–6. https://doi.org/10.12968/jowc.1922.214.171.124910
- 31.Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clin Dermatol. 2007;25(1):9–18. https://doi.org/10.1016/j.clindermatol.2006.09.007.CrossRefPubMedGoogle Scholar
- 39.Kumar V, Cotran RZ, Robbins SL. Basic pathology. 7th ed. Philadelphia: Saunders; 2003. p. 873.Google Scholar
- 46.Brandner JM, Haftek M, Niessen CM. Adherens junctions, desmosomes and tight junctions in epidermal barrier function. Open Dermatol J. 2010;4:14–20.Google Scholar