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In vivo evaluation of bacterial cellulose/acrylic acid wound dressing hydrogel containing keratinocytes and fibroblasts for burn wounds

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Abstract

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.

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References

  1. Sen S, Greenhalgh D, Palmieri T. Review of burn injury research for the year 2009. J Burn Care Res. 2010;31(6):836–48. https://doi.org/10.1097/BCR.0b013e318200ccb6.

    Article  PubMed  Google Scholar 

  2. Fagenholz PJ, Sheridan RL, Harris NS, Pelletier AJ, Camargo CA. National study of emergency department visits for burn injuries, 1993 to 2004. J Burn Care Res. 2007;28(5):681–90. https://doi.org/10.1097/BCR.0B013E318148C9AC.

    Article  PubMed  Google Scholar 

  3. Gibran NS, Wiechman S, Meyer W, Edelman L, Fauerbach J, Gibbons L, et al. Summary of the 2012 ABA Burn Quality Consensus Conference. J Burn Care Res. 2013;34(4):361–85. https://doi.org/10.1097/BCR.0b013e31828cb249.

    Article  PubMed  Google Scholar 

  4. Oryan A, Jalili M, Kamali A. Tissue engineering in burn wound healing: current modalities and future directions. Int Clin Pathol J. 2017;4(1):00085.

    Article  Google Scholar 

  5. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Crit Care. 2015;19(1):243. https://doi.org/10.1186/s13054-015-0961-2.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kumar RJ, Kimble RM, Boots R, Pegg SP. Treatment of partial-thickness burns: a prospective, randomized trial using Transcyte. ANZ J Surg. 2004;74(8):622–6. https://doi.org/10.1111/j.1445-1433.2004.03106.x.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 2007;127(5):998–1008. https://doi.org/10.1038/sj.jid.5700786.

    Article  CAS  PubMed  Google 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

  11. Takei T, Nakahara H, Ijima H, Kawakami K. Synthesis of a chitosan derivative soluble at neutral pH and gellable by freeze thawing, and its application in wound care. Acta Biomater. 2012;8(2):686–93. https://doi.org/10.1016/j.actbio.2011.10.005.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  13. Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. 2003;24(24):4337–51. https://doi.org/10.1016/S0142-9612(03)00340-5.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google Scholar 

  16. Cacicedo ML, Castro MC, Servetas I, Bosnea L, Boura K, Tsafrakidou P, et al. Progress in bacterial cellulose matrices for biotechnological applications. Bioresour Technol. 2016;213:172–80. https://doi.org/10.1016/j.biortech.2016.02.071.

    Article  CAS  PubMed  Google Scholar 

  17. Fu L, Zhang J, Yang G. Present status and applications of bacterial cellulose-based materials for skin tissue repair. Carbohydr Polym. 2013;92(2):1432–42. https://doi.org/10.1016/j.carbpol.2012.10.071.

    Article  CAS  PubMed  Google 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.

    Article  CAS  Google 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.

    Article  CAS  PubMed  Google 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

  22. Klemm D, Schumann D, Udhardt U, Marsch S. Bacterial synthesized cellulose—artificial blood vessels for microsurgery. Prog Polym Sci. 2001;26(9):1561–603. https://doi.org/10.1016/S0079-6700(01)00021-1.

    Article  CAS  Google Scholar 

  23. Mohamad N, Mohd Amin MC, Pandey M, Ahmad N, Rajab NF. Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model. Carbohydr Polym. 2014;114:312–20. https://doi.org/10.1016/j.carbpol.2014.08.025.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.1999.8.8.25910

  30. Qiu Y, Qiu L, Cui J, Wei Q. Bacterial cellulose and bacterial cellulose-vaccarin membranes for wound healing. Mater Sci Eng C Mater Biol Appl. 2016;59:303–9. https://doi.org/10.1016/j.msec.2015.10.016.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  32. Arai M, Matsuzaki T, Ihara S. Wound closure on the neonatal rat skin I. The modulation of the thickness of epidermis at the closing incisional wounds. CellBio. 2013;2(4):248–56. https://doi.org/10.4236/cellbio.2013.24027.

    Article  Google Scholar 

  33. Boateng JS, Matthews KH, Stevens HN, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci. 2008;97(8):2892–923. https://doi.org/10.1002/jps.21210.

    Article  CAS  PubMed  Google Scholar 

  34. Lorenti A. Wound healing: from epidermis culture to tissue engineering. CellBio. 2012;1(02):17–29. https://doi.org/10.4236/cellbio.2012.12003.

    Article  CAS  Google Scholar 

  35. Madaghiele M, Demitri C, Sannino A, Ambrosio L. Polymeric hydrogels for burn wound care: advanced skin wound dressings and regenerative templates. Burns Trauma. 2014;2(4):153–61. https://doi.org/10.4103/2321-3868.143616.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005;6(4):328–40. https://doi.org/10.1038/nrm1619.

    Article  CAS  PubMed  Google Scholar 

  37. Smiley AK, Klingenberg JM, Boyce ST, Supp DM. Keratin expression in cultured skin substitutes suggests that the hyperproliferative phenotype observed in vitro is normalized after grafting. Burns. 2006;32(2):135–8. https://doi.org/10.1016/j.burns.2005.08.017.

    Article  PubMed  Google Scholar 

  38. Byrne C, Tainsky M, Fuchs E. Programming gene expression in developing epidermis. Development. 1994;120(9):2369–83.

    CAS  PubMed  Google Scholar 

  39. Kumar V, Cotran RZ, Robbins SL. Basic pathology. 7th ed. Philadelphia: Saunders; 2003. p. 873.

    Google Scholar 

  40. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314–21. https://doi.org/10.1038/nature07039.

    Article  CAS  PubMed  Google Scholar 

  41. Darby I, Skalli O, Gabbiani G. Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Investig. 1990;63(1):21–9.

    CAS  PubMed  Google Scholar 

  42. Desmouliere A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 2004;48(5–6):509–17. https://doi.org/10.1387/ijdb.041802ad.

    Article  CAS  PubMed  Google Scholar 

  43. Serini G, Gabbiani G. Mechanisms of myofibroblast activity and phenotypic modulation. Exp Cell Res. 1999;250(2):273–83. https://doi.org/10.1006/excr.1999.4543.

    Article  CAS  PubMed  Google Scholar 

  44. Darby IA, Laverdet B, Bonte F, Desmouliere A. Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014;7:301–11. https://doi.org/10.2147/CCID.S50046.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Desmouliere A, Redard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol. 1995;146(1):56–66.

    CAS  PubMed  PubMed Central  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.

    CAS  Google Scholar 

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Funding

This work was supported by funding from Universiti Kebangsaan Malaysia (GP-K007818 and DIP-2015-026).

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Correspondence to Mohd Cairul Iqbal Mohd Amin.

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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.

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Mohamad, N., Loh, E.Y.X., Fauzi, M.B. et al. In vivo evaluation of bacterial cellulose/acrylic acid wound dressing hydrogel containing keratinocytes and fibroblasts for burn wounds. Drug Deliv. and Transl. Res. 9, 444–452 (2019). https://doi.org/10.1007/s13346-017-0475-3

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