Skip to main content

Advertisement

Log in

Hemostasis for Severe Hemorrhage with Photocrosslinkable Chitosan Hydrogel and Calcium Alginate

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

In patients with severe hemorrhage, complications such as shock or death may occur if the patient is not treated appropriately and expeditiously. To create a hemostat kit for severe hemorrhage, ultraviolet light irradiation was applied to photocrosslinkable chitosan hydrogel and calcium alginate. As a hemorrhage model, the femoral arteries and veins of anesthetized rats were cut. Hemodynamics and hematological parameters including red blood cell (RBC) count, hemoglobin concentration, hematocrit, white blood cell (WBC) count, and platelet count, and serum parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as a marker of hemostasis. In rats for which no procedure was used, death occurred within 30 min. By using the hydrogel hemostat, the survival rate rose to 75% or more. RBC count, hemoglobin, hematocrit, and platelet levels were not significantly changed for 3 days. WBC count increased 1 day after hemostasis. AST and ALT increased 1 day after hemostasis, but it decreased 3 days later. The photocrosslinkable chitosan hydrogel and calcium alginate were biodegraded at 3 and 28 days, respectively, by neutrophils and keratinocyte chemoattractant.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Acosta, J. A., J. C. Yang, R. J. Winchell, R. K. Simons, D. A. Fortlage, P. Hollingsworth-Fridlund, and D. B. Hoyt. Lethal injuries and time to death in a level I trauma center. J. Am. Coll. Surg. 186(5):528–533, 1998.

    Article  CAS  PubMed  Google Scholar 

  2. Alam, H. B., D. Burris, J. A. DaCorta, and P. Rhee. Hemorrhage control in the battlefield: role of new hemostatic agents. Mil. Med. 170(1):63–69, 2005.

    PubMed  Google Scholar 

  3. Austin, S. K. Haemostasis. Medicine 37(3):133–136, 2009.

    Article  Google Scholar 

  4. Benesch, J., and P. Tengvall. Blood protein adsorption onto chitosan. Biomaterials 23(12):2561–2568, 2002.

    Article  CAS  PubMed  Google Scholar 

  5. Champion, H. R., R. F. Bellamy, C. P. Roberts, and A. Leppaniemi. A profile of combat injury. J. Trauma 54(5 Suppl):S13–S19, 2003.

    PubMed  Google Scholar 

  6. Chandy, T., and C. P. Sharma. Chitosan—as a biomaterial. Biomater. Artif. Cells Artif. Organs 18(1):1–24, 1990.

    CAS  PubMed  Google Scholar 

  7. Chou, T. C., E. Fu, C. J. Wu, and J. H. Yeh. Chitosan enhances platelet adhesion and aggregation. Biochem. Biophys. Res. Commun. 302(3):480–483, 2003.

    Article  CAS  PubMed  Google Scholar 

  8. Duerbeck, N. B., D. G. Chaffin, and P. Coney. Platelet and hemorrhagic disorders associated with pregnancy: a review. Part I. Obstet. Gynecol. Surv. 52(9):575–584, 1997.

    Article  CAS  PubMed  Google Scholar 

  9. Gardner, R. L. Application of alginate gels to the study of Mammalian development. Methods Mol. Biol. 254:383–392, 2004.

    PubMed  Google Scholar 

  10. Hirano, S. Chitin biotechnology applications. Biotechnol. Annu. Rev. 2:237–258, 1996.

    Article  CAS  PubMed  Google Scholar 

  11. Ishihara, M., K. Ono, M. Sato, K. Nakanishi, Y. Saito, H. Yura, T. Matsui, H. Hattori, M. Fujita, M. Kikuchi, and A. Kurita. Acceleration of wound contraction and healing with a photocrosslinkable chitosan hydrogel. Wound Repair Regener. 9(6):513–521, 2001.

    Article  CAS  Google Scholar 

  12. Ishihara, M., K. Nakanishi, K. Ono, M. Sato, M. Kikuchi, Y. Saito, H. Yura, T. Matsui, H. Hattori, M. Uenoyama, and A. Kurita. Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials 23(3):833–840, 2002.

    Article  CAS  PubMed  Google Scholar 

  13. Kauvar, D. S., R. Lefering, and C. E. Wade. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J. Trauma 60(6 Suppl):S3–S11, 2006.

    Article  PubMed  Google Scholar 

  14. Kheirabadi, B. S., M. R. Scherer, J. S. Estep, M. A. Dubick, and J. B. Holcomb. Determination of efficacy of new hemostatic dressings in a model of extremity arterial hemorrhage in swine. J. Trauma 67(3):450–460, 2009.

    Article  CAS  PubMed  Google Scholar 

  15. Kheirabadi, B. S., J. W. Edens, I. B. Terrazas, J. S. Estep, H. G. Klemcke, M. A. Dubick, and J. B. Holcomb. Comparison of new hemostatic granules/powders with currently deployed hemostatic products in a lethal model of extremity arterial hemorrhage in swine. J. Trauma 66(2):316–326, 2009.

    Article  PubMed  Google Scholar 

  16. Kozen, B. G., S. J. Kircher, J. Henao, F. S. Godinez, and A. S. Johnson. An alternative hemostatic dressing: comparison of CELOX, HemCon, and QuikClot. Acad. Emerg. Med. 15(1):74–81, 2008.

    Article  PubMed  Google Scholar 

  17. Mori, T., M. Okumura, M. Matsuura, K. Ueno, S. Tokura, Y. Okamoto, S. Minami, and T. Fujinaga. Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. Biomaterials 18(13):947–951, 1997.

    Article  CAS  PubMed  Google Scholar 

  18. Muzzarelli, R. A. A. Biochemical significance of exogenous chitins and chitosans in animals and patients. Carbohydr. Polym. 20(1):7–16, 1993.

    Article  CAS  Google Scholar 

  19. Nishimura, K., C. Ishihara, S. Ukei, S. Tokura, and I. Azuma. Stimulation of cytokine production in mice using deacetylated chitin. Vaccine 4(3):151–156, 1986.

    Article  CAS  PubMed  Google Scholar 

  20. Ono, K., Y. Saito, H. Yura, K. Ishikawa, A. Kurita, T. Akaike, and M. Ishihara. Photocrosslinkable chitosan as a biological adhesive. J. Biomed. Mater. Res. 49(2):289–295, 2000.

    Article  CAS  PubMed  Google Scholar 

  21. Ono, K., M. Ishihara, Y. Ozeki, H. Deguchi, M. Sato, Y. Saito, H. Yura, M. Sato, M. Kikuchi, A. Kurita, and T. Maehara. Experimental evaluation of photocrosslinkable chitosan as a biologic adhesive with surgical applications. Surgery 130(5):844–850, 2001.

    Article  CAS  PubMed  Google Scholar 

  22. Park, C. J., N. P. Gabrielson, D. W. Pack, R. D. Jamison, and A. J. W. Wagoner. The effect of chitosan on the migration of neutrophil-like HL60 cells, mediated by IL-8. Biomaterials 30(4):436–444, 2009.

    Article  CAS  PubMed  Google Scholar 

  23. Rao, S. B., and C. P. Sharman. Use of chitosan as a biomaterial: studies on its safety and hemostatic potential. J. Biomed. Mater. Res. 34(1):21–28, 1997.

    Article  CAS  PubMed  Google Scholar 

  24. Sauaia, A., F. A. Moore, E. E. Moore, K. S. Moser, R. Brennan, R. A. Read, and P. T. Pons. Epidemiology of trauma deaths: a reassessment. J. Trauma 38(2):185–193, 1995.

    Article  CAS  PubMed  Google Scholar 

  25. Shigemasa, Y., and S. Minami. Applications of chitin and chitosan for biomaterials. Biotechnol. Genet. Eng. Rev. 13:383–420, 1996.

    CAS  PubMed  Google Scholar 

  26. Thatte, H. S., S. Zagarins, S. F. Khuri, and T. H. Fischer. Mechanisms of poly-N-acetyl glucosamine polymer-mediated hemostasis: platelet interactions. J. Trauma 57(1 Suppl):S13–S21, 2004.

    Article  CAS  PubMed  Google Scholar 

  27. Thomas, S. Alginate dressings in surgery and wound management: Part 1. J. Wound Care 9:56–60, 2000.

    CAS  PubMed  Google Scholar 

  28. Thomas, S. Alginate dressings in surgery and wound management—Part 2. J. Wound Care 9:115–119, 2000.

    CAS  PubMed  Google Scholar 

  29. van Eijk, M., C. P. van Roomen, G. H. Renkema, A. P. Bussink, L. Andrews, E. F. Blommaart, A. Sugar, A. J. Verhoeven, R. G. Boot, and J. M. Aerts. Characterization of human phagocyte-derived chitotriosidase, a component of innate immunity. Int. Immunol. 17(11):1505–1512, 2005.

    Article  PubMed  Google Scholar 

  30. Ward, K. R., M. H. Tiba, W. H. Holbert, C. R. Blocher, G. T. Draucker, E. K. Proffitt, G. L. Bowlin, R. R. Ivatury, and R. F. Diegelmann. Comparison of a new hemostatic agent to current combat hemostatic agents in a Swine model of lethal extremity arterial hemorrhage. J. Trauma 63(2):276–284, 2007.

    Article  PubMed  Google Scholar 

  31. Wedmore, I., J. G. McManus, A. E. Pusateri, and J. B. Holcomb. A special report on the chitosan-based hemostatic dressing: experience in current combat operations. J. Trauma 60(3):655–658, 2006.

    Article  PubMed  Google Scholar 

  32. Whang, H., W. Kirsch, Y. Zhu, C. Yang, and S. Hudson. Hemostatic agents derived from chitin and chitosan. J. Macromol. Sci. C Poly. Rev. 45(4):309–323, 2005.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Yaizu Suisankagaku Industry Co., Ltd., for supplying photocrosslinkable chitosan hydrogel. We thank Ms. Ishida for proofreading. We thank Mr. Furukawa and Mr. Kuroda for their fresh advice.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. Hattori.

Additional information

Associate Editor Smadar Cohen oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hattori, H., Amano, Y., Nogami, Y. et al. Hemostasis for Severe Hemorrhage with Photocrosslinkable Chitosan Hydrogel and Calcium Alginate. Ann Biomed Eng 38, 3724–3732 (2010). https://doi.org/10.1007/s10439-010-0121-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-010-0121-4

Keywords

Navigation