SpringerLink
Log in

Injectable hydrogel incorporated with poly(hexamethylene biguanide) and deep eutectic solvent as linker and highly efficient antibacterial agents for bacteria-infected burnt wound

  • Original Research
  • Published:
Iranian Polymer Journal Aims and scope Submit manuscript

Abstract

Minor and severe burn injuries are common and highly complicated pathology causing huge mortality and costly wound treatment protocols. In this work, an injectable microgel assembly was developed to accelerate burn wound healing rate and quality where the network formation occurred after injection of the precursor on the wound bed. Poly(hexamethylene biguanide) (PHMB), an amine-containing antibacterial polymer, was synthesized and functioned as a linker of microgels by the addition of a specific deep eutectic solvent (DES) as a catalyst for particles connection. The major function of the eutectic mixture was to assist in the cross-linking of the microgels; however, it could play as an antibacterial agent against Gram + bacteria. The THDES was prepared by the reaction of arginine with ascorbic acid (Asc), and glycerol ([DES]Arg/G,A), two of which are known as the components involved in the wound healing process. Depending on the PHMB concentration, the microgel assembly experienced a gel-to-sol transition under shear stresses ranging from 104 to 105 Pa and exhibited much stronger antibacterial activities as the fraction of PHMB increased. Application of the developed hydrogel promoted healing of the infected burned rat, enhanced re-epithelialization, and attenuated the formation of fibrotic scar tissue.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Spain)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

Similar content being viewed by others

References

  1. Bakadia M, Lamboni L, Ahmed Q, Zheng R, Boni O, Shi Z, Yang G (2023) Antibacterial silk sericin/poly(vinyl alcohol) hydrogel with antifungal property for potential infected large burn wound healing: systemic evaluation. Smart Mater Med 4:37–58

    Article  Google Scholar 

  2. Dong Y, Cui M, Qu J, Wang X, Kwon SH, Barrera J, Gurtner G (2020) Conformable hyaluronic acid hydrogel delivers adipose-derived stem cells and promotes regeneration of burn injury. Acta Biomater 108:56–66

    Article  CAS  PubMed  Google Scholar 

  3. Ng JY, Zhu X, Mukherjee D, Zhang C, Hong S, Kumar Y, Ee PL (2021) Pristine gellan gum–collagen interpenetrating network hydrogels as mechanically enhanced anti-inflammatory biologic wound dressings for burn wound therapy. ACS Appl Biomater 4:1470–1482

    Article  CAS  Google Scholar 

  4. Margolis DJ, Gupta J, Hoffstad O, Papdopoulos M, Glick HA, Thom SR, Mitra N (2013) Lack of effectiveness of hyperbaric oxygen therapy for the treatment of diabetic foot ulcer and the prevention of amputation: a cohort study. Diabetes Care 36:1961–1966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hartmann DD, Martins RP, da Silva TC, Stefanello ST, Courtes AA, Gonçalves DF, Furtado ABV, Duarte BSL, Signori LU, Soares FAA, Puntel GO (2021) Oxidative stress is involved in LLLT mechanism of action on skin healing in rats. Braz J Med Biol Res 54:1–9

    Article  Google Scholar 

  6. Tehrani FK, Sheikhi M, Rafiemanzelat F, Esmaeili F, Ghodsi S, Koohmareh GA, Ghalavand B (2022) Protein and polysaccharide-based asymmetric mat with tuned bilayer configuration for enhanced wound healing efficiency. Carbohydr Polym 292:119666

    Article  CAS  PubMed  Google Scholar 

  7. Shakiba M, Sheikhi M, Pahnavar Z, Tajiki A, Bigham A, Foroozandeh A, Abdouss M (2023) Development of an antibacterial and antioxidativenanofibrous membrane using curcumin-loaded halloysite nanotubes for smart wound healing: In vitro and in vivo studies. Int J Pharm 642:123207

    Article  CAS  PubMed  Google Scholar 

  8. Shahriari-Khalaji M, Sattar M, Cao R, Zhu M (2023) Angiogenesis, hemocompatibility and bactericidal effect of bioactive natural polymer-based bilayer adhesive skin substitute for infected burned wound healing. Bioact Mater 29:177–195

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Bhatnagar P, Law JX, Ng SF (2022) Delivery systems for platelet derived growth factors in wound healing: a review of recent developments and global patent landscape. J Drug Deliv Sci Technol 71:103270

    Article  CAS  Google Scholar 

  10. Yao Y, Zhang A, Yuan C, Chen X, Liu Y (2021) Recent trends on burn wound care: hydrogel dressings and scaffolds. Biomater Sci 9:4523–4540

    Article  CAS  PubMed  Google Scholar 

  11. Alavi M, Nokhodchi A (2022) Antimicrobial and wound healing activities of electrospun nanofibers based on functionalized carbohydrates and proteins. Cellulose 29:1331–1347

    Article  CAS  Google Scholar 

  12. Zia T, Usman M, Sabir A, Shafiq M, Khan RU (2020) Development of inter-polymeric complex of anionic polysaccharides, alginate/k-carrageenan bio-platform for burn dressing. Int J Biol Macromol 157:83–95

    Article  CAS  PubMed  Google Scholar 

  13. Qazi TH, Burdick JA (2021) Granular hydrogels for endogenous tissue repair. Bioprocess Biosyst Eng 1:1–3

    Google Scholar 

  14. Feng Q, Li D, Li Q, Cao X, Dong H (2022) Microgel assembly: Fabrication, characteristics and application in tissue engineering and regenerative medicine. Bioact Mater 9:105–119

    CAS  PubMed  Google Scholar 

  15. Feng Q, Li D, Li Q, Li S, Huang H, Li H, Dong H, Cao X (2022) Dynamic nanocomposite microgelassembly with microporosity, injectability, tissue-adhesion, and sustained drug release promotes articular cartilage repair and regeneration. Adv Healthc Mater 11:e2102395

    Article  PubMed  Google Scholar 

  16. Cui T, Yu J, Wang CF, Chen S, Li Q, Guo K, Qing R, Wang G, Ren J (2022) Micro-gel ensembles for accelerated healing of chronic wound via pH regulation. Adv Sci 9:1–12

    Article  CAS  Google Scholar 

  17. Sheikhi M, Rafiemanzelat F, Moroni L, Setayeshmehr M (2021) Ultrahigh-water-content biocompatible gelatin-based hydrogels: Toughened through micro-sized dissipative morphology as an effective strategy. Mater Sci Eng C 120:1–15

    Article  Google Scholar 

  18. Sheikhi M, Rafiemanzelat F, Sadeghpour N, Shams M, Esfahani AN (2021) Deep eutectic solvents based on l-Arginine and glutamic acid as green catalysts and conductive agents for epoxy resins. J Mol Liq 343:117568

    Article  CAS  Google Scholar 

  19. Sheikhi M, Rafiemanzelat F, Ghodsi S, Moroni L, Setayeshmehr M (2022) 3D printing of jammed self-supporting microgels with alternative mechanism for shape fidelity, crosslinking and conductivity. Addit Manuf 58:102997

    CAS  Google Scholar 

  20. Rahman MS, Roy R, Jadhav B, Hossain MN, Halim MA, Raynie DE (2021) Formulation, structure, and applications of therapeutic and amino acid-based deep eutectic solvents: an overview. J Mol Liq 321:3761–3776

    Article  Google Scholar 

  21. Değim Z, Çelebi N, Alemdaroğlu C, Deveci M, Öztürk S, Özoğul C (2011) Evaluation of chitosan gel containing liposome-loaded epidermal growth factor on burn wound healing. Int Wound J 8:343–354

    Article  PubMed  PubMed Central  Google Scholar 

  22. Rana MM, Rahman MS, Ullah MA, Siddika A, Hossain ML, Akhter MS, Hasan MZ, Asaduzzaman SM (2020) Amnion and collagen-based blended hydrogel improves burn healing efficacy on a rat skin wound model in the presence of wound dressing biomembrane. Biomed Mater Eng 31:1–17

    CAS  PubMed  Google Scholar 

  23. Xu C, Molino BZ, Wang X, Cheng F, Xu W, Molino P, Bacher M, Su D, Rosenau T, Willför S, Wallace G (2018) 3D printing of nanocellulose hydrogel scaffolds with tunable mechanical strength towards wound healing application. J Mater Chem B 6:7066–7075

    Article  CAS  PubMed  Google Scholar 

  24. Ousey K, Cutting KF, Rogers AA, Rippon MG (2016) The importance of hydration in wound healing: reinvigorating the clinical perspective. J Wound Care 25:122–130

    Article  CAS  PubMed  Google Scholar 

  25. Rousselle P, Montmasson M, Garnier C (2019) Extracellular matrix contribution to skin wound re-epithelialization. Matrix Biol 75:12–26

    Article  PubMed  Google Scholar 

  26. Veith AP, Henderson K, Spencer A, Sligar AD, Baker AB (2019) Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev 146:97–125

    Article  CAS  PubMed  Google Scholar 

  27. Morgan FL, Moroni L, Baker MB (2020) Dynamic bioinks to advance bioprinting. Adv Healthc Mater 9:1–18

    Article  Google Scholar 

  28. Moores J (2013) Vitamin C: a wound healing perspective. Br J Community Nurs 18:S6–S11

    Article  Google Scholar 

  29. Zhou Y, Liu G, Huang H, Wu J (2021) Advances and impact of arginine-based materials in wound healing. J Mater Chem B 9:6738–6750

    Article  CAS  PubMed  Google Scholar 

  30. Taysun MB, Sert E, Atalay FS (2016) Physical properties of benzyl tri-methyl ammonium chloride based deep eutectic solvents and employment as catalyst. J Mol Liq 223:845–852

    Article  CAS  Google Scholar 

  31. Wikene KO, Rukke HV, BruzellE THH (2017) Investigation of the antimicrobial effect of natural deep eutectic solvents (NADES) as solvents in antimicrobial photodynamic therapy. J Photochem Photobiol B Biol 171:27–33

    Article  CAS  Google Scholar 

  32. Alshameri AW, Owais M (2022) Antibacterial and cytotoxic potency of the plant-mediated synthesis of metallic nanoparticles Ag NPs and ZnO NPs: a review. Open Nano 8:1–23

    Google Scholar 

  33. Tian EK, Wang Y, Ren R, Zheng W, Liao W (2021) Gold nanoparticle: recent progress on its antibacterial applications and mechanisms. J Nanomater 2021:1–18

    Article  Google Scholar 

  34. Yousefi SR, Alshamsi HA, Amiri O, Salavati-Niasari M (2021) Synthesis, characterization and application of Co/Co3O4 nanocomposites as an effective photocatalyst for discoloration of organic dye contaminants in wastewater and antibacterial properties. J Mol Liq 337:1–10

    Article  Google Scholar 

  35. Singh TA, Sharma A, Tejwan N, Ghosh N, Das J, Sil PC (2021) A state of the art review on the synthesis, antibacterial, antioxidant, antidiabetic and tissue regeneration activities of zinc oxide nanoparticles. Adv Colloid Interface Sci 295:1–23

    Article  Google Scholar 

  36. Menazea AA, Ahmed MK (2020) Synthesis and antibacterial activity of graphene oxide decorated by silver and copper oxide nanoparticles. J Mol Struct 1218:1–27

    Article  Google Scholar 

  37. Albukhaty S, Al-Bayati L, Al-Karagoly H, Al-Musawi S (2022) Preparation and characterization of titanium dioxide nanoparticles and in vitro investigation of their cytotoxicity and antibacterial activity against Staphylococcus aureus and Escherichia coli. Anim Biotechnol 33:864–870

    Article  CAS  PubMed  Google Scholar 

  38. Lai PL, Hong DW, Ku KL, Lai ZT, Chu IM (2014) Novel thermosensitive hydrogels based on methoxy polyethylene glycol-co-poly(lactic acid-co-aromatic anhydride) for cefazolin delivery. Nanotechnol Biol Med 10:553–560

    Article  CAS  Google Scholar 

  39. Posadowska U, Brzychczy-Wloch M, Pamula E (2016) Injectable gellan gum-based nanoparticles-loaded system for the local delivery of vancomycin in osteomyelitis treatment. J Mater Sci Mater Med 27:1–9

    Article  CAS  Google Scholar 

  40. Wang X, Liu Z, Ye X, Hu K, Zhong H, Yuan X, **ong H, Guo Z (2015) A facile one-pot method to two kinds of graphene oxide-based hydrogels with broad-spectrum antimicrobial properties. Chem Eng J 260:331–337

    Article  CAS  Google Scholar 

  41. Venkatesan J, Jayakumar R, Mohandas A, Bhatnagar I, Kim SK (2014) Antimicrobial activity of chitosan-carbon nanotube hydrogels. Materials 7:3946–3955

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  42. Li S, Dong S, Xu W, Tu S, Yan L, Zhao C, Ding J, Chen X (2018) Antibacterial hydrogels. Adv Sci 5:1–17

    Article  ADS  Google Scholar 

  43. Ndlovu SP, Ngece K, Alven S, Aderibigbe BA (2021) Gelatin-based hybrid scaffolds: promising wound dressings. Polymers 13:1–31

    Article  Google Scholar 

  44. Brauer E, Lippens E, Klein O, Nebrich G, Schreivogel S, Korus G, Petersen A (2019) Collagen fibrils mechanically contribute to tissue contraction in an in vitro wound healing scenario. Adv Sci 6:1801780

    Article  Google Scholar 

  45. Mathew-Steiner SS, Roy S, Sen CK (2021) Collagen in wound healing. Bioengineering 8:1–15

    Article  Google Scholar 

Download references

Acknowledgements

Appreciation is extended to the Office of Vice Chancellor for Research and Technology of the University of Isfahan. Technical support by Dr. SiamakBeheshti for In Vivo Evaluations from the Department of Plant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Tissue Engineering and Regenerative Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, 143591647, Iran

    Masoud Ghorbani

  2. Department of Dermatology, Baqiyatallah University of Medical Sciences, Tehran, 143591647, Iran

    Seyyed Masoud Davoudi

  3. Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, 143591647, Iran

    Hadi Esmaeili Gouvarchinghaleh

  4. Department of Plant and Animal Biology, Faculty of Biological Sciences and Technology, University of Isfahan, Isfahan, 817467344, Iran

    Latifeh Malekmohammad

Authors
  1. Masoud Ghorbani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyyed Masoud Davoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hadi Esmaeili Gouvarchinghaleh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Latifeh Malekmohammad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Masoud Ghorbani or Hadi Esmaeili Gouvarchinghaleh.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghorbani, M., Davoudi, S.M., Gouvarchinghaleh, H.E. et al. Injectable hydrogel incorporated with poly(hexamethylene biguanide) and deep eutectic solvent as linker and highly efficient antibacterial agents for bacteria-infected burnt wound. Iran Polym J 33, 419–434 (2024). https://doi.org/10.1007/s13726-023-01262-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13726-023-01262-w

Keywords

Search

Navigation