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Preparation and Characterization of Trimethyl Chitosan /Hyaluronic Acid Composite Encapsulated with LL37 to Promote Wound Healing in an Animal Model

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Abstract

Wound treatment is one of the most prevalent concerns and economic burden in healthcare system. Because of antibacterial and re-epithelialization properties, trimethyl chitosan (TMC) has the potential to be used in wound healing dressing. Hyaluronic acid (HA), the main component of the extracellular matrix is capable to activate specific cell signals involved in fibroblast proliferation and new vessel formation, improving the quality of the scars. LL37 peptide promotes wound healing, angiogenesis and also has potential antimicrobial properties. Hence, we aimed to fabricate LL37 encapsulated in TMC-HA composite as a novel topical wound dressing and evaluated its efficacy to accelerate wound closure in an animal model. Composites were optimized based on physical properties such as, porosity, swelling, biodegradation, and mechanical properties. The release of LL37 from the optimized composite (3:3 v/v) was completed during 8 h using bicinchoninic acid assay (BCA) protein quantification kit. LL37-loaded TMC-HA composites displayed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Animal experiments demonstrated the complete wound healing in the group that received LL37-loaded TMC-HA following 16 days of treatment. Based on histological studies, the formation of advanced granulation tissue with significantly higher collagen deposition and re-epithelialized tissues were observed in LL37-loaded TMC-HA-treated wounds. In conclusion, we successfully developed a biodegradable wound healing dressing that promoted healing processes in mice wound model contributed to simultaneous positive effects of the polymers and LL37.

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References

  • Akita S (2019) Wound repair and regeneration: mechanisms, signaling int. J Mol Sci 20:6328

    Article  Google Scholar 

  • Boateng J, Catanzano O (2015) Advanced Therapeutic Dressings for Effective Wound Healing—A Review. J Pharm Sci 104:3653–3680

    Article  CAS  PubMed  Google Scholar 

  • Carretero M, Marı´a J, Escamez 1 et al (2008) In vitro and in vivo Wound Healing-Promoting activities of human cathelicidin LL-37. J Invest Dermatology 128:223–236

  • Chanda A, Adhikari J, Ghosh A et al (2018) Electrospun chitosan/polycaprolactone-hyaluronic acid bilayered scaffold for potential wound healing applications. 116:774–785

  • Chereddy K, Her C, Comune M et al (2014) PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing. J Controlled Release 194:138–147

    Article  CAS  Google Scholar 

  • Dehkordi N, Minaiyan M, Talebi et al (2019) Nanocrystalline cellulose–hyaluronic acid composite enriched with GMCSF loaded chitosan nanoparticles for enhanced wound healing. Biomedical Materials,, p 14

  • Fahimirad Sh H, Sarlak N (2021) Antimicrobial Activity, Stability and Wound Healing Performances of Chitosan Nanoparticles Loaded Recombinant LL37 Antimicrobial Peptide

  • Garcia-Orue I, Gainza G, Girbau C (2016) LL37 loaded nanostructured lipid carriers (NLC): a new strategy for the topical treatment of chronic wounds. Eur J Pharm Biopharm 108:310–316

    Article  CAS  PubMed  Google Scholar 

  • Ghomi E, Khalili Sh, Khorasani S, Nisiang R (2019) Wound dressings: current advances and future directions. J Appl Polym Sci 136:47738

    Article  Google Scholar 

  • Grönberg A, Mahlapuu M, Ståhle M et al (2014) Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Rep Reg 22:613–621

    Article  Google Scholar 

  • Kahlenberg JM, Kaplan MJ (2013) Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease. J Immunol. 15;191:4895 – 901.

  • Lin J, Zhang H, Chen Z et al (2010) Penetration of lipid membranes by gold nanoparticles: insights into Cellular Uptake, cytotoxicity, and their relationship. 4:5421–5429ACS Nano

  • Lukas B, Hallstensson K, Ringstad L et al (2019) Cubosomes for topical delivery of the antimicrobial peptide LL-37. Eur J Pharm Biopharm 134:60–67

    Article  Google Scholar 

  • Mangoni M, Alison, Dermott M, Zasloff M (2016) Antimicrobial peptides and wound healing: biological and therapeutic considerations experimental dermatology. 25:167–173

  • Miguel S, Moreira A, Correia I (2019) Chitosan based-asymmetric membranes for wound healing: a review. Int J Biol Macromol 127:460–475

    Article  CAS  PubMed  Google Scholar 

  • Mohandas A, Anisha KP, Chennazhi R, Jayakumar (2015) Chitosan–hyaluronic acid/VEGF loaded fibrin nanoparticles compositesponges for enhancing angiogenesis in wounds. Colloids Surf B 127:105–113

    Article  CAS  Google Scholar 

  • Murphy P, Evans G (2012) Advances in Wound Healing: a review of current wound Healing Products. https://doi.org/10.1155/2012/190436. Plastic surgery international

  • Nathan C (2020) Resisting antimicrobial resistance. Nat Rev Microbio l18:259–260

    Article  Google Scholar 

  • Neuma M, Nanau R, Oruña-Sanchez L (2015) Hyaluronic Acid and Wound Healing. J Pharm Pharm Sci 18:53–60

    Article  Google Scholar 

  • Pivodová V, Franková J, Galandáková A et al (2015) Vitro AuNPs’ cytotoxicity and their. Effect on Wound Healing, Nanobiomedicine

    Google Scholar 

  • Ramosa R, Silva J, Rodriguesa A et al (2011) Wound healing activity of the human antimicrobial peptide LL37, peptides. 32:1469–1476

  • Rezazadeh M, Akbari V, Amuaghae E, Emami J (2018a) Preparation and characterization of an injectable thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin. Res Pharm Sci 13:181

    Article  PubMed  PubMed Central  Google Scholar 

  • Rezazadeh M, Jafari N, Akbari V (2018b) A mucoadhesive thermosensitive hydrogel containing erythropoietinmas a potential treatment in oral mucositis: in vitro and in vivo studies drug delivery and Translational Research. 8:1226–1237

  • Saporito P, Mouritzen M, Olesen A et al (2018) LL-37 fragments have antimicrobial activity against Staphylococcus epidermidis biofilms and wound healing potential in HaCaT cell lineJ Pep Sci.;e3080

  • Teh B, Shen Y, Friedland L (2012) A review on the use of hyaluronic acid in tympanic membrane wound healing Expert Opinion on Biological Therapy. 12:23–36

  • Thapa R, Diep D, Tønnesen H (2020) Topical antimicrobial peptide formulations for wound healing: current developments and future prospects. Acta Biomater 103:52–67

    Article  CAS  PubMed  Google Scholar 

  • Zheng Z, Dong Y, Cheng X (2016) Biomaterials based on N,N,N-trimethyl chitosan fibers in wound dressing applications. Int J Biol Macromol 89:471–476

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics and Novel drug delivery system research center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Mahboubeh Rezazadeh, Iman Jalali & Azade Taheri

  2. Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Vajihe Akbari

  3. Department of pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohsen Minaiyan

  4. Terasaki Institute for Biomedical Innovation (TIBI), Los Angeles, CA, 90064, USA

    Alireza Hassani Najafabadi

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  1. Mahboubeh Rezazadeh
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  2. Iman Jalali
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  3. Vajihe Akbari
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  4. Mohsen Minaiyan
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  5. Alireza Hassani Najafabadi
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  6. Azade Taheri
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Correspondence to Mahboubeh Rezazadeh.

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Rezazadeh, M., Jalali, I., Akbari, V. et al. Preparation and Characterization of Trimethyl Chitosan /Hyaluronic Acid Composite Encapsulated with LL37 to Promote Wound Healing in an Animal Model. Int J Pept Res Ther 29, 43 (2023). https://doi.org/10.1007/s10989-023-10513-6

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  • DOI: https://doi.org/10.1007/s10989-023-10513-6

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