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Development of Responsive Chitosan–Genipin Hydrogels for the Treatment of Wounds

  • Abitha M. Heimbuck
    Abitha M. Heimbuck
    Department of Biomedical Engineering, Louisiana Tech University, Ruston, Louisiana 71272, United States
  • Tyler R. Priddy-Arrington
    Tyler R. Priddy-Arrington
    Department of Biomedical Engineering, Louisiana Tech University, Ruston, Louisiana 71272, United States
  • Madison L. Padgett
    Madison L. Padgett
    Department of Biomedical Engineering, Louisiana Tech University, Ruston, Louisiana 71272, United States
  • Claire B. Llamas
    Claire B. Llamas
    Department of Pharmacology, Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70118, United States
  • Haley H. Barnett
    Haley H. Barnett
    School of Biological Sciences, Louisiana Tech University, Ruston, Louisiana 71272, United States
  • Bruce A. Bunnell
    Bruce A. Bunnell
    Department of Pharmacology, Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70118, United States
  • , and 
  • Mary E. Caldorera-Moore*
    Mary E. Caldorera-Moore
    Department of Biomedical Engineering, Louisiana Tech University, Ruston, Louisiana 71272, United States
    *E-mail: [email protected]. Tel: +1(318)257-2207. Fax: +1(318)257-4000.
Cite this: ACS Appl. Bio Mater. 2019, 2, 7, 2879–2888
Publication Date (Web):June 18, 2019
https://doi.org/10.1021/acsabm.9b00266
Copyright © 2019 American Chemical Society
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Abstract

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Chronic wounds are characterized by an increased bacterial presence, alkaline pH, and excessive wound drainage. Hydrogel biomaterials composed of the carbohydrate polymer chitosan are advantageous for wound healing applications because of their innate antimicrobial and hemostatic properties. Here, genipin-cross-linked–chitosan hydrogels were synthesized and characterized, and their in vitro and in vivo performances were evaluated as a viable wound dressing. Characterization studies demonstrate that the developed chitosan–genipin hydrogels were able to neutralize an environmental pH, while averaging ∼230% aqueous solution uptake, demonstrating their use as a perfusive wound dressing. Bacterial activity studies demonstrate the hydrogels’ ability to hinder Escherichia coli growth by ∼70%, while remaining biocompatible in vitro to fibroblast and keratinocyte cells. Furthermore, chitosan–genipin hydrogels promote an enhanced immune response and cellular proliferation in induced pressure wounds in mice. All together, these results reflect the potential of the developed hydrogels to be used as a proactive wound dressing.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsabm.9b00266.

  • Methods and results of chitosan–genipin hydrogel formation absorbance, solid-state 13C nuclear magnetic resonance spectroscopy of chitosan–genipin hydrogels, and chitosan–genipin hydrogel swelling and pH profile in phosphate buffered saline (PDF)

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Cited By


This article is cited by 9 publications.

  1. Haiwang Lai, Shan Liu, Jieyu Yan, Feiyue Xing, Pu Xiao. Facile Fabrication of Biobased Hydrogel from Natural Resources: l-Cysteine, Itaconic Anhydride, and Chitosan. ACS Sustainable Chemistry & Engineering 2020, 8 (12) , 4941-4947. https://doi.org/10.1021/acssuschemeng.0c00774
  2. Gonçalo Oliveira, Idalina Gonçalves, Cláudia Nunes, Paula Ferreira, Manuel A. Coimbra, Céline Martin, Julien Bras. Feasibility of chitosan crosslinked with genipin as biocoating for cellulose-based materials. Carbohydrate Polymers 2020, 242 , 116429. https://doi.org/10.1016/j.carbpol.2020.116429
  3. Xiaohong Chu, Fan Wu, Baohong Sun, Ming Zhang, Saijie Song, Pan Zhang, Yuli Wang, Qicheng Zhang, Ninglin Zhou, Jian Shen. Genipin cross-linked carbon dots for antimicrobial, bioimaging and bacterial discrimination. Colloids and Surfaces B: Biointerfaces 2020, 190 , 110930. https://doi.org/10.1016/j.colsurfb.2020.110930
  4. Jinxi Xiang, Lan Shen, Yanlong Hong. Status and future scope of hydrogels in wound healing: Synthesis, materials and evaluation. European Polymer Journal 2020, 130 , 109609. https://doi.org/10.1016/j.eurpolymj.2020.109609
  5. Kartik Ravishankar, Raghavachari Dhamodharan. Advances in chitosan-based hydrogels: Evolution from covalently crosslinked systems to ionotropically crosslinked superabsorbents. Reactive and Functional Polymers 2020, 149 , 104517. https://doi.org/10.1016/j.reactfunctpolym.2020.104517
  6. Sneha S. Rao, Jayachandran Venkatesan, Ashwini Prabhu, P.D. Rekha. Natural polymeric biomaterials in growth factor delivery for treating diabetic foot ulcers. Journal of Drug Delivery Science and Technology 2020, 55 , 101385. https://doi.org/10.1016/j.jddst.2019.101385
  7. Minghao Zhang, Shiyan Chen, Li Zhong, Baoxiu Wang, Huaping Wang, Feng Hong. Zn2+-loaded TOBC nanofiber-reinforced biomimetic calcium alginate hydrogel for antibacterial wound dressing. International Journal of Biological Macromolecules 2020, 143 , 235-242. https://doi.org/10.1016/j.ijbiomac.2019.12.046
  8. Parinaz Sabourian, Mandana Tavakolian, Hossein Yazdani, Masoud Frounchi, Theo G.M. van de Ven, Dusica Maysinger, Ashok Kakkar. Stimuli-responsive chitosan as an advantageous platform for efficient delivery of bioactive agents. Journal of Controlled Release 2020, 317 , 216-231. https://doi.org/10.1016/j.jconrel.2019.11.029
  9. Xin Feng, Hongjie Dai, Liang Ma, Yong Yu, Mi Tang, Yuan Li, Weijie Hu, Tingwei Liu, Yuhao Zhang. Food-Grade Gelatin Nanoparticles: Preparation, Characterization, and Preliminary Application for Stabilizing Pickering Emulsions. Foods 2019, 8 (10) , 479. https://doi.org/10.3390/foods8100479

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