Comparative Analysis of Collagen and Chitosan-based Dressing for Haemostatic and Wound Healing Application

AAPS PharmSciTech volume 22, Article number: 76 (2021) Cite this article

Abstract

Collagen and chitosan have haemostatic, tissue fix and wound healing properties but the poor mechanical property limits their application. Therefore, various concentrations of collagen (1–6%) and chitosan (1–2%) were used to develop biopolymer-coated gauzes, with and without glycerol as plasticiser. Glycerol-treated gauzes showed desired mechanical and adhesive property in comparison to polymer-coated gauzes alone. Developed gauzes were characterized using differential scanning calorimetry, thermal gravimetric analysis and Fourier transform infrared spectrophotometry to confirm the biopolymer coating and stability. Scanning electron microscopy showed multilayer coating of the biopolymer and faster clotting in chitosan gauzes in comparison to collagen. Surface plasmon resonance assay confirmed that chitosan exhibited more binding affinity of 65 RU in comparison to collagen, which showed 55 RU with erythrocytes. Decrease in the value of plateletcrit and mean platelet volume confirmed platelet adhesion and aggregation over the surface of polymer-coated dressings. Gamma scintigraphy studies showed 85 ± 2% formulation retention up to 12 h at the wound site in comparison to 40 ± 3% retention of the radiopharmaceutical alone. Collagen and chitosan-coated gauze showed 226 ± 15 s and 179 ± 12 s haemostasis time, respectively, which was significantly less from 506 ± 15 s in standard gauze. Chitosan gauze showed faster wound healing in comparison to the collagen-coated gauze. Chitosan and collagen-coated gauzes showed 55 ± 4% wound contraction on day seven in comparison to 25 ± 2% in the control group, while chitosan gauzes showed complete wound contraction on day fourteenth, while the collagen-coated gauze showed 90 ± 3% on the same day.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

REFERENCES

  1. 1.

    Achneck HE, Sileshi B, Jamiolkowski RM, Albala DM, Shapiro ML, Lawson JH. A comprehensive review of topical haemostatic agents: efficacy and recommendations for use. Ann Surg. 2010;251:217–28.

    Article  Google Scholar 

  2. 2.

    Sauaia AMD, Moore FAMD, Moore EEMD, Moser KSPRA, Brennan RRNMS, Read RAMD, et al. Epidemiology of trauma deaths. Epidemiology of trauma deaths: a reassessment. J Trauma Inj Infect Crit Care. 1995;38(2):185–93.

  3. 3.

    Hirshberg A, Wall MJ, Ramchandani MK, Mattox KL. Re-operation for bleeding in trauma. Arch Surg. 1993;128:1163–7.

    CAS  Article  Google Scholar 

  4. 4.

    Enoch S, Leaper DJ. Basic science of wound healing. Surgery (Oxford). 2005;26:31–7.

    Article  Google Scholar 

  5. 5.

    Ong S-Y, Wu J, Moochhala SM, Tan M-H, Lu J. Development of a chitosan based wound dressing with improved Haemostatic and antimicrobial properties. Biomaterials. 2008;29:4323–32.

    CAS  Article  Google Scholar 

  6. 6.

    Pusateri AE, Kheirabadi BS, Delgado AV, Doyle JW, Kanellos J, Uscilowicz JM. Structural design of the dry fibrin sealant dressing and its impact on the haemostatic efficacy of the product. J Biomed Mater Res B Appl Biomater. 2004;70:114–21.

    Article  Google Scholar 

  7. 7.

    Pusateri AE, Modrow HE, Harris RA, Holcomb JB, Hess JR, Mosebar RH. Advanced haemostatic dressing development program: animal model selection criteria and results of a study of nine Haemostatic dressings in a model of severe large venous hemorrhage and hepatic injury in swine. J Trauma. 2003;55:518–26.

    CAS  Article  Google Scholar 

  8. 8.

    Liu X, Ma L, Mao Z, Gao C. Chitosan-based biomaterials for tissue repair and regeneration. Chitosan for biomaterials II. In: Jayakumar R, Prabaharan M, Muzzarelli RAA, editors. Advances in polymer science. Heidelberg: Springer Berlin; 2011. p. 81–127.

    Google Scholar 

  9. 9.

    Rao SB, Sharma CP. Use of chitosan as a biomaterial: studies on its safety and haemostatic potential. J Biomed Mater Res. 1997;34:21–8.

    CAS  Article  Google Scholar 

  10. 10.

    Ghica MV, Albu MG, Popa L, Moisescu S. Response surface methodology and Taguchi approach to assess the combined effect of formulation factors on minocycline delivery from collagen sponges. Pharmazie. 2013;68:340–8.

    CAS  PubMed  Google Scholar 

  11. 11.

    Ghica MV, Albu MG, Leca M, Popa L, Moisescu S. Design and optimization of some collagen-minocycline based hydrogels potentially applicable for the treatment of cutaneous wounds infections. Pharmazie. 2011;66:853–61.

    CAS  PubMed  Google Scholar 

  12. 12.

    Antoniac IV, Albu MG, Antoniac A, Rusu LC, Ghica MV. Collagen-bioceramic smart composites. In: Antoniac IV, editor. Handbook of bioceramics and biocomposites. Basel: Springer; 2016.

    Google Scholar 

  13. 13.

    Albu MG. Collagen gels and matrices for biomedical applications. Saarbrücken: Lambert Academic Publishing; 2011. ISBN 978-01-9850-970-7

    Google Scholar 

  14. 14.

    Lee CH, Lee Y. Collagen-based formulations for wound healing applications. In: Agren M, editor. Wound healing biomaterials, vol. 2. Cambridge: Woodhead Publishing, Elsevier; 2016. p. 135–49. ISBN 978-1-78242-456-7.

    Google Scholar 

  15. 15.

    De Almeida EB, Cardoso JC, Lima a AKD, Oliveira a NLD, Pontes-Filho c NTD, Lima a SO, Souza a ICL, Cavalcanti de RL, Júnior a AJ. The incorporation of Brazilian propolis into collagen-based dressing films improves dermal burn healing. J Ethnopharmacology. 2013;147:419–25.

  16. 16.

    Akturk O, Tezcaner A, Bilgili H, Deveci MS, Gecit MR, Keskin D. Evaluation of sericin/collagen membranes as prospective wound dressing biomaterial. J Biosci Bioeng. 2011;112:279–88.

    CAS  Article  Google Scholar 

  17. 17.

    Aranaz I, Harris R, Heras A. Chitosan amphiphilic derivatives. Chemistry and applications. Curr Org Chem. 2010;14:308–30.

    CAS  Article  Google Scholar 

  18. 18.

    Chatelet C, Damour O, Domard A. Influence of the degree of acetylation on some biological properties of chitosan films. Biomaterials. 2000;22:261–8.

    Article  Google Scholar 

  19. 19.

    Pusateri AE, Holcomb JB, Harris RA, MacPhee MJ, Charles NC, Beall LD. Effect of fibrin bandage fibrinogen concentration on blood loss after grade V liver injury in swine. Mil Med. 2001;166:217–22.

    CAS  Article  Google Scholar 

  20. 20.

    Brian TG. Effects of Celox and trauma DEX on hemorrhage control in a porcine model. AANA J. 2010;78(2):115–20.

    Google Scholar 

  21. 21.

    Mercy HP, Halim AS, Hussein AR. Chitosan-derivatives as haemostatic agents: their role in tissue regeneration. Regen Res. 2012;1:38–46.

    Google Scholar 

  22. 22.

    Arafat MT, Tronci G, Yin J, Wood DJ, Russell SJ. Biomimetic wet-stable fibres via wet spinning and diacid-based crosslinking of collagen triple helices. Polymer. 2015;77:102–12.

    CAS  Article  Google Scholar 

  23. 23.

    Tronci G, Grant CA, Thomson NH, Russell SJ, Wood DJ. Multi-scale mechanical characterization of highly swollen photo-activated collagen hydrogels. J R Soc Interface. 2015;12:20141079.

    Article  Google Scholar 

  24. 24.

    Tronci G, Doyle A, Russell SJ, Wood DJ. Structure-property-function relationships in triple-helical collagen hydrogels. Mater Res Soc Symp Proc. 2013;1498:145–50.

    Article  Google Scholar 

  25. 25.

    Wedmore I, McManus JG, Pusateri AE, Holcomb JB. A special report on the chitosan based haemostatic dressing: experience in current combat operations. J Trauma. 2006;60:6558.

    Article  Google Scholar 

  26. 26.

    Rhee P, Brown C, Martin M, Salim A, Plurad D, Green D. QuikClot use in trauma for hemorrhage control: case series of 103 documented uses. J Trauma. 2008;64:1093–9.

    Article  Google Scholar 

  27. 27.

    Bettini R, Romani AA, Morganti MM, Borghetti AF. Physicochemical and cell adhesion properties of chitosan films prepared from sugar and phosphate containing solutions. Eur J Pharm Biopharm. 2008;68:74–81.

    CAS  Article  Google Scholar 

  28. 28.

    Park BK, Kim MM. Applications of chitin and its derivatives in biological medicine. Int J Mol Sci. 2010;11:5152–64.

  29. 29.

    Hunt TK, Beckert S. Therapeutical and practical aspects of oxygen in wound healing. In: Lee B, editor. The wound management manual. New York: McGraw-Hill Medical. 2000;44–54.

  30. 30.

    Rydzak J, Kaczmarek R, Czerwinski M, Lukasiewicz J, Tyborowska J. The Baculovirus-expressed binding region of Plasmodium falciparum EBA-140 ligand and its Glycophorin C binding specificity. PLoS One. 2015;10(1):e0115437.

    Article  Google Scholar 

  31. 31.

    Tsukada K, Tokunaga K, Iwama T, Mishima Y. The pH changes of pressure ulcers related to the healing process of wounds. Wounds. 1992;4(1):16–20.

    Google Scholar 

  32. 32.

    de Lima JM, Sarmento RR, de Souza JR, Brayner FA, Feitosa APS, Padilha R, et al. Evaluation of hemagglutination activity of chitosan nanoparticles using human erythrocytes. Biomed Res Int. 2015; I.D.247965, 1–6.

  33. 33.

    Pogorielov M, Kalinkevich O, Deineka V, Garbuzova V, Solodovnik A, Kalinkevich A, et al. Haemostatic chitosan coated gauze: in vitro interaction with human blood and in-vivo effectiveness. Biomater Res. 2015;19(22):1–6.

  34. 34.

    Chhabra P, Tyagi P, Bhatnagar A, Mittal G, Kumar A. Optimization, characterization, and efficacy evaluation of 2% chitosan scaffold for tissue engineering and wound healing. J Pharm Bioallied Sci. 2016;8:300–8.

    CAS  Article  Google Scholar 

  35. 35.

    Sharma A, Fish BL, Moulder JE, Medhora M, Baker JE, Mader M, et al. Safety and blood sample volume and quality of a refined retro-orbital bleeding technique in rats using a lateral approach. Lab Anim. 2014;43(2):63–6.

    Article  Google Scholar 

  36. 36.

    https://www.oecd-ilibrary.org/environment/test-no-404-acute-dermalirritation_corrosion _9789264070622-en.

  37. 37.

    Pan H, Fan D, Cao W, Zhu C, Duan Z, Fu R, et al. Preparation and characterization of breathable hemostatic hydrogel dressings and determination of their effects on full-thickness defects. Polymers. 2017;9:727.

    Article  Google Scholar 

  38. 38.

    Schneider LA, Korber A, Grabbe S, Dissemond J. Influence of pH on wound-healing: a new perspective for wound-therapy? Arch Dermatol Res. 2007;298:413–20.

    Article  Google Scholar 

  39. 39.

    Stavitsky AB. Micromethods for the study of proteins and antibodies. I. Procedure and general applications of hemagglutination and hemagglutination-inhibition reactions with tannic acid and protein-treated red blood cells. J Immunol. 1954;72(5):360–7.

    CAS  PubMed  Google Scholar 

  40. 40.

    Sixma JJ, Wester J. The Haemostatic plug. Semin Hematol. 1977;14:265–99.

    CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGEMENTS

This work was supported by a grant from the Institute of Nuclear Medicine and Allied Sciences-Defence Research and Development Organization (INMAS-DRDO), New Delhi. Grant No. INM/321.

Author information

Affiliations

  1. Divison of Nuclear Medicines, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, 110054, India

    Divya Tripathi, Harish Rawat, Gaurav Mittal, Abhinav Jamini & Amit Tyagi

  2. Center for Biomedical Engineering, Indian Institute of Technology, New Delhi, 110016, India

    Divya Tripathi & Harpal Singh

  3. Department of Pharmacology, KIET Group of Institutions, Ghaziabad, U.P., 201206,, India

    Kartikey Rastogi

  4. Department of Basic and Applied Sciences, School of Engineering and Sciences, G.D. Goenka University, Gurugram, Haryana, 122103, India

    Priyanka Tyagi

  5. Department of Combat Sciences, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, 110054, India

    Amit Tyagi

Authors
  1. Divya Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kartikey Rastogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Priyanka Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harish Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gaurav Mittal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abhinav Jamini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Harpal Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amit Tyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amit Tyagi.

Ethics declarations

Conflict of Interest

The writers proclaimed no conflicts of interest as for the research, authorship and publication of this article.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tripathi, D., Rastogi, K., Tyagi, P. et al. Comparative Analysis of Collagen and Chitosan-based Dressing for Haemostatic and Wound Healing Application. AAPS PharmSciTech 22, 76 (2021). https://doi.org/10.1208/s12249-021-01944-9

Download citation

KEY WORDS

  • biopolymer
  • collagen
  • chitosan
  • gamma scintigraphy
  • haemostasis