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Microwaved bacterial cellulose-based hydrogel microparticles for the healing of partial thickness burn wounds

Abstract

Burn wound management is a complex process because the damage may extend as far as the dermis which has an acknowledged slow rate of regeneration. This study investigates the feasibility of using hydrogel microparticles composed of bacterial cellulose and polyacrylamide as a dressing material for coverage of partial-thickness burn wounds. The microparticulate carrier structure and surface morphology were investigated by Fourier transform infrared, X-ray diffraction, elemental analysis, and scanning electron microscopy. The cytotoxicity profile of the microparticles showed cytocompatibility with L929 cells. Dermal irritation test demonstrated that the hydrogel was non-irritant to the skin and had a significant effect on wound contraction compared to the untreated group. Moreover, histological examination of in vivo burn healing samples revealed that the hydrogel treatment enhanced epithelialization and accelerated fibroblast proliferation with wound repair and intact skin achieved by the end of the study. Both the in vitro and in vivo results proved the biocompatibility and efficacy of hydrogel microparticles as a wound dressing material.

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References

  1. 1.

    Church D, El Sayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev. 2006;19(2):403–34.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Mogoşanu GD, Grumezescu AM. Natural and synthetic polymers for wounds and burns dressing. Int J Pharm. 2014;463:127–36.

    Article  PubMed  Google Scholar 

  3. 3.

    Pham C, Greenwood J, Cleland H, Woodruff P, Maddern G. Bioengineered skin substitutes for the management of burns: a systematic review. Burns. 2007;33:946–57.

    Article  PubMed  Google Scholar 

  4. 4.

    Lootens L, Brusselaers N, Beele H, Monstrey S. Keratinocytes in the treatment of severe burn injury: an update. Int Wound J. 2012;10:6–12.

    Article  PubMed  Google Scholar 

  5. 5.

    Lin W, Lien C, Yeh H, Yu C, Hsu S. Bacterial cellulose and bacterial cellulose-chitosan membranes for wound dressing applications. Carbohydr Polym. 2013;94:603–11.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Kwak MH, Kim JE, Go J, Koh EK, Song SH, Son HJ, Kim HS, Yun YH, Jung YJ, Hwang DY. Bacterial cellulose membrane produced by Acetobacter sp. A10 for burn wound dressing applications. Carbohyd Polym. 2015;122:387–98.

    CAS  Article  Google Scholar 

  7. 7.

    Huang S, Fu X. Naturally derived materials-based cell and drug delivery systems in skin regeneration. J Control Release. 2010;142:149–59.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Silvestre AJD, Freire CSR, Neto CP. Do bacterial cellulose membranes have potential in drug-delivery systems? Expert Opin Drug Deliv. 2014;11:1113–24.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Czaja W, Krystynowicz A, Bielecki S, Brown Jr RM. Microbial cellulose—the natural power to heal wounds. Biomaterials. 2006;27:145–51.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Backdahl H, Risberg B, Gatenholm P. Observations on bacterial cellulose tube formation for application as vascular graft. Mater. Sci. Eng. C mater. Biol. Appl. 2011;31(1):14–21.

    Google Scholar 

  11. 11.

    Hennink WE, Van Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2012;64:223–36.

    Article  Google Scholar 

  12. 12.

    Jovanovic J, Adnadjevic B. Influence of microwave heating on the kinetics of acrylic acid polymerization and crosslinking. J Appl Poly Sci. 2010;116:55–63.

    CAS  Article  Google Scholar 

  13. 13.

    Zhao Z, Zhong L, Qibin X, Hongxia X, Yuesheng L. Fast synthesis of temperature-sensitive PNIPAAm hydrogels by microwave irradiation. Eur Poly J. 2008;44:1217–24.

    CAS  Article  Google Scholar 

  14. 14.

    Pandey M, Mohamad N, Amin MCIM. Bacterial cellulose/acrylamide pH-sensitive smart hydrogel: development, characterization, and toxicity studies in ICR mice model. Mol Pharm. 2014;11:3596–608.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Amin MCIM, Abadi AG, Katas H. Purification, characterization and comparative studies of spray-dried bacterial cellulose microparticles. Carbohydr Polym. 2014;99:180–9.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Ahmad N, Amin MCIM, Mahali SM, Ismail I, Chuang VTG. Biocompatible and mucoadhesive bacterial cellulose-g-poly (acrylic acid) hydrogels for oral protein delivery. Mol Pharm. 2014;11:4130–42.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Amjad MW, Amin MCI, Katas H, Butt AM. Doxorubicin-loaded cholic acid polyethyleneimine micelles for targeted delivery of antitumor drugs: synthesis, characterization, and evaluation of their in-vitro cytotoxicity. Nanoscale Res Lett. 2012;7:687–789.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Loo Y, Wong Y, Cai EZ, Ang C, Raju A, Lakshmanan A, Koh AG, Zhou HJ, Lim T, Moochhala SM, Hauser CAE. Ultrashort peptide nanofibrous hydrogels for the acceleration of healing of burn wounds. Biomaterials. 2014;35:1–10.

    Article  Google Scholar 

  19. 19.

    Alsarra IA. Chitosan topical gel formulation in the management of burn wounds. Int J Biol Macromol. 2009;45:16–21.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Amin MCIM, Ahmad N, Halib N, Ahmad I. Synthesis and characterization of thermo and pH responsive bacterial cellulose/acrylic acid hydrogel for drug delivery. Carbohydr Polym. 2012;88:465–73.

    Article  Google Scholar 

  21. 21.

    Pandey M, Amin MCI, Ahmad N, Abeer MM. Rapid synthesis of superabsorbent smart-swelling bacterial cellulose/acrylamide-based hydrogels for drug delivery. Int J Polym Sci. 2013;2013:1–10.

    Article  Google Scholar 

  22. 22.

    Song Y, Zhou J, Zhang L, Wu X. Homogenous modification of cellulose with acrylamide in NaOH/urea aqueous solutions. Carbohydr Polym. 2008;73:18–25.

    CAS  Article  Google Scholar 

  23. 23.

    Marandi GB, Esfandiari K, Biranvand F, Babapour M, Sadeh S, Mahdavinia GR. pH sensitivity and swelling behavior of partially hydrolyzed formaldehyde-crosslinked poly (acrylamide) superabsorbent hydrogels. J App Polym Sci. 2008;109:1083–92.

    CAS  Article  Google Scholar 

  24. 24.

    Kumar A, Singh K, Ahuja M. Xanthan-g-poly (acrylamide): microwave assisted synthesis, characterization and in-vitro release behavior. Carbohydr Polym. 2009;76:261–7.

    CAS  Article  Google Scholar 

  25. 25.

    Sutar PB, Mishra RK, Pal K, Banthia AK. Development of pH sensitive polyacrylamide grafted pectin hydrogel for controlled drug delivery system. J Mater Sci Mater Med. 2008;19:2247–53.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Vijan V, Kaity S, Biswas S, Isaac J, Ghosh A. Microwave assisted synthesis and characterization of acrylamide grafted gellan, application in drug delivery. Carbohydr Polym. 2012;90:496–506.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Ibrahim M, El S, Mamdouh AM, Abdel AM, Dawidar AM, Hugh DCS. Biodegradable pH-responsive alginate-poly (lactic-co-glycolic acid) nano/micro hydrogel matrices for oral delivery of silymarin. Carbohydr Polym. 2011;83:1345–54.

    Article  Google Scholar 

  28. 28.

    Liu X, Tang M, Zhang T, Hu Y, Zhang S, Kong L, Xue Y. Determination of a threshold dose to reduce or eliminate cdte-induced toxicity in l929 cells by controlling the exposure dose. PLoS One. 2013;8:e59359. doi:10.1371/journal.pone.0059359.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Baek HS, Ja YY, Dong WH, Dong HL, Oh-Hun K, Jong-Chul P. Evaluation of the extraction method for the cytotoxicity testing of latex gloves. Yonsei Med J. 2005;46:579–83.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Almeida IF, Pereira T, Silva NHCS. Bacterial cellulose membranes as drug delivery systems: an in vivo skin compatibility study. Eur J Pharm Biopharm. 2014;106:264–9.

    Google Scholar 

  31. 31.

    Muangman P, Opasanon S, Suwanchot S, Thangthed O. Efficiency of microbial cellulose dressing in partial-thickness burn wounds. J Am Col Certif Wound Spec. 2011;27; 3(1):9–16.

    Google Scholar 

  32. 32.

    Cai Z, Kim J. Bacterial cellulose/poly(ethylene glycol) composite: characterization and first evaluation of biocompatibility. Cellulose. 2010;17(1):83–91.

    CAS  Article  Google Scholar 

  33. 33.

    Anon. Amended final report on the safety assessment of polyacrylamide and acrylamide residues in cosmetics. Int J Toxicol. 2005;2:21–50.

    Google Scholar 

  34. 34.

    Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci. 2008;97:2892–923.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Junker JPE, Kamel RA, Caterson EJ, Eriksson E. Clinical impact upon wound healing and inflammation in moist, wet, and dry environments. Adv Wound Care. 2013;2:348–56.

    Article  Google Scholar 

  36. 36.

    Mohamad N, Amin MCIM, Pandey M, Ahmad N, Rajab N. Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model. Carbohyd Polym. 2014;114:312–20.

    CAS  Article  Google Scholar 

  37. 37.

    Tepole AB, Kuhl E. Systems-based approaches toward wound healing. Pediatr Res. 2013;73:553–63.

    Article  Google Scholar 

  38. 38.

    Chen S, Tsao C, Chang C, Lai Y, Wu M, Chuang C, Chou H, Wang C, Hsieh K. Assessment of reinforced poly (ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model. Mater Sci Eng C, Mater Biol Appl. 2013;33:2584–94.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Ministry of Higher Education, Malaysia (UKM-Farmasi-02-FRGS0192-2010) and the Universiti Kebangsaan Malaysia (INOVASI-2013-005) for their financial assistance and support.

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Correspondence to Mohd Cairul Iqbal Mohd Amin.

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Pandey, M., Mohamad, N., Low, WL. et al. Microwaved bacterial cellulose-based hydrogel microparticles for the healing of partial thickness burn wounds. Drug Deliv. and Transl. Res. 7, 89–99 (2017). https://doi.org/10.1007/s13346-016-0341-8

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Keywords

  • Hydrogel microparticles
  • Bacterial cellulose
  • Cytotoxicity
  • Partial-thickness burn wound
  • Microwave irradiation