Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Complete prevention of blood loss with self-sealing haemostatic needles

Nature Materials volume 16, pages 147–152 (2017)Cite this article

Subjects

Abstract

Bleeding is largely unavoidable following syringe needle puncture of biological tissues and, while inconvenient, this typically causes little or no harm in healthy individuals. However, there are certain circumstances where syringe injections can have more significant side effects, such as uncontrolled bleeding in those with haemophilia, coagulopathy, or the transmission of infectious diseases through contaminated blood. Herein, we present a haemostatic hypodermic needle able to prevent bleeding following tissue puncture. The surface of the needle is coated with partially crosslinked catechol-functionalized chitosan that undergoes a solid-to-gel phase transition in situ to seal punctured tissues. Testing the capabilities of these haemostatic needles, we report complete prevention of blood loss following intravenous and intramuscular injections in animal models, and 100% survival in haemophiliac mice following syringe puncture of the jugular vein. Such self-sealing haemostatic needles and adhesive coatings may therefore help to prevent complications associated with bleeding in more clinical settings.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Physicochemical characteristics of CHI-C-coated needles.
Figure 2: Haemostatic capability of the self-sealing needles for two in vivo models.
Figure 3: Analysis of the extent of oxidation of CHI-C.
Figure 4: Clinical benefits of self-sealing haemostatic needles for a haemophilia model.

Similar content being viewed by others

References

  1. Pereira, J. & Phan, T. Management of bleeding in patients with advanced cancer. Oncologist 9, 561–570 (2004).

    Article  Google Scholar 

  2. Prandoni, P. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100, 3484–3488 (2002).

    Article  CAS  Google Scholar 

  3. Domm, J. A., Hudson, M. G. & Janco, R. L. Complications of central venous access devices in paediatric haemophilia patients. Haemophilia 9, 50–56 (2003).

    Article  CAS  Google Scholar 

  4. Doerfler, M. E., Kaufman, B. & Goldenberg, A. S. Central venous catheter placement in patients with disorders of haemostasis. Chest 110, 185–188 (1996).

    Article  CAS  Google Scholar 

  5. Srivastava, A. et al. Guidelines for the management of haemophilia. Haemophilia 19, 1–47 (2013).

    Article  Google Scholar 

  6. Chee, Y. L., Crawford, J. C., Watson, H. G. & Greaves, M. Guidelines on the assessment of bleeding risk prior to surgery or invasive procedures. Br. J. Haematol. 140, 496–504 (2008).

    CAS  Google Scholar 

  7. De Boulle, K. & Heydenrych, I. Patient factors influencing dermal filler complications: prevention, assessment, and treatment. Clin. Cosmet. Invest. Dermatol. 8, 205–214 (2015).

    Article  Google Scholar 

  8. Batorova, A. & Martinowitz, U. Intermittent injections vs. continuous infusion of Factor VIII in haemophilia patients undergoing major surgery. Br. J. Haematol. 110, 715–720 (2000).

    CAS  Google Scholar 

  9. World Federation of Hemophilia Report on the Annual Global Survey 2014 (World Federation of Hemophilia, 2015).

  10. Plug, I. et al. Mortality and causes of death in patients with haemophilia, 1992–2001 a prospective cohort study. J. Thromb. Haemost. 4, 510–516 (2006).

    Article  CAS  Google Scholar 

  11. Prausnitz, M. R. Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 56, 581–587 (2004).

    Article  CAS  Google Scholar 

  12. Sherman, A. et al. Suppression of inhibitor formation against FVIII in a murine model of haemophilia A by oral delivery of antigens bioencapsulated in plant cells. Blood 124, 1659–1668 (2014).

    Article  CAS  Google Scholar 

  13. Lisbeth Illum, L. Nasal drug delivery-possibilities, problems and solutions. J. Control. Release 87, 187–198 (2003).

    Article  Google Scholar 

  14. Hong, S. et al. Air/Water interfacial formation of freestanding, stimuli-responsive, self-healing catecholamine Janus-faced microfilms. Adv. Mater. 26, 7581–7587 (2014).

    Article  CAS  Google Scholar 

  15. Ryu, J. H., Jo, S., Koh, M. & Lee, H. Bio-inspired, water-soluble to insoluble self-conversion for flexible, biocompatible, transparent, catecholamine polysaccharide thin films. Adv. Funct. Mater. 24, 7709–7716 (2014).

    Article  CAS  Google Scholar 

  16. Kastrup, C. J. et al. Painting blood vessels and atherosclerotic plaques with an adhesive drug depot. Proc. Natl Acad. Sci. USA 109, 21444–21449 (2012).

    Article  CAS  Google Scholar 

  17. Ong, S.-Y., Wu, J., Moochhala, S. M., Tan, M.-H. & Lu, J. Development of a chitosan-based wound dressing with improved haemostatic and antimicrobial properties. Biomaterials 29, 4323–4332 (2008).

    Article  CAS  Google Scholar 

  18. Whang, H. S., Kirsch, W., Zhu, Y. H., Yang, C. Z. & Hudson, S. M. Haemostatic agents derived from chitin and chitosan. J. Macromol. Sci. Polym. Rev. 45, 309–323 (2005).

    Article  Google Scholar 

  19. Kim, K., Kim, K., Ryu, J. H. & Lee, H. Chitosan-catechol: a polymer with long-lasting mucoadhesive properties. Biomaterials 52, 161–170 (2015).

    Article  CAS  Google Scholar 

  20. Ryu, J. H. et al. Catechol-functionalized chitosan/pluronic hydrogels for issue adhesives and haemostatic materials. Biomacromolecules 12, 2633–2659 (2011).

    Article  Google Scholar 

  21. Mizoguchi, Y. et al. Changes in blood parameters in New Zealand White rabbits during pregnancy. Lab. Anim. 44, 33–39 (2010).

    Article  CAS  Google Scholar 

  22. Russell, K. E. et al. Reduced bleeding events with subcutaneous administration of recombinant human factor IX in immune-tolerant haemophilia B dogs. Blood 102, 4393–4398 (2003).

    Article  CAS  Google Scholar 

  23. Hauck, T. S., Anderson, R. E., Fischer, H. C., Newbigging, S. & Chan, W. C. W. In vivo quantum-dot toxicity assessment. Small 6, 138–144 (2010).

    Article  CAS  Google Scholar 

  24. Zhang, X.-D. et al. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int. J. Nanomedicine 5, 771–781 (2010).

    Article  CAS  Google Scholar 

  25. Zhang, Y., Thomas, Y., Kim, E. & Payne, G. F. pH- and voltage-responsive chitosan hydrogel through covalent cross-linking with catechol. J. Phys. Chem. B 116, 1579–1585 (2012).

    Article  CAS  Google Scholar 

  26. Wang, S. X. et al. A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains. Science 273, 1078–1084 (1996).

    Article  CAS  Google Scholar 

  27. Xia, J., Xu, Y., Lin, J. & Hu, B. UV-induced polymerization of urushiol without photoinitiator. Prog. Org. Coat. 61, 7–10 (2008).

    Article  CAS  Google Scholar 

  28. Anh, N. V. & Williams, R. M. Bis-semiquinone (bi-radical) formation by photoinduced proton coupled electron transfer in covalently linked catechol–quinone systems: Aviram’s hemiquinones revisited. Photochem. Photobiol. Sci. 11, 957–961 (2012).

    Article  Google Scholar 

  29. Tindale, C. R. Reactions of biogenic amines with quinones. Aust. J. Chem. 37, 611–617 (1984).

    Article  CAS  Google Scholar 

  30. Xua, X., Wanga, L., Guoa, S., Lei, L. & Tang, T. Surface chemical study on the covalent attachment of hydroxypropyltrimethyl ammonium chloride chitosan to titanium surfaces. Appl. Surf. Sci. 257, 10520–10528 (2011).

    Article  Google Scholar 

  31. Amaral, I. F., Granja, P. L. & Barbosa, M. A. Chemical modification of chitosan by phosphorylation: an XPS, FT-IR and SEM study. J. Biomater. Sci. Polym. Edn. 16, 1575–1593 (2005).

    Article  CAS  Google Scholar 

  32. Lee, H., Scherer, N. F. & Messersmith, P. B. Single-molecule mechanics of mussel adhesion. Proc. Natl Acad. Sci. USA 103, 12999–13003 (2006).

    Article  CAS  Google Scholar 

  33. Ahn, B. K., Lee, D. W., Israelachvili, J. N. & Waite, J. H. Surface-initiated self-healing of polymers in aqueous media. Nat. Mater. 13, 867–872 (2014).

    Article  CAS  Google Scholar 

  34. Miller, D. R. et al. Mussel coating protein-derived complex coacervates mitigate frictional surface damage. ACS Biomater. Sci. Eng. 1, 1121–1128 (2015).

    Article  CAS  Google Scholar 

  35. Bardelmeijer, H. A. et al. Cannulation of the jugular vein in mice: a method for serial withdrawal of blood samples. Lab. Anim. 37, 181–187 (2003).

    Article  CAS  Google Scholar 

  36. Parasuraman, S., Raveendran, R. & Kesavan, R. Blood sample collection in small laboratory animals. J. Pharmacol. Pharmacother. 1, 87–93 (2010).

    Article  CAS  Google Scholar 

  37. Bollard, C. M., Teague, L. R., Berry, E. W. & Ockelford, P. A. The use of central venous catheters (portacaths) in children with haemophilia. Haemophilia 6, 66–70 (2000).

    Article  CAS  Google Scholar 

  38. Miller, K. et al. Implantable venous access devices in children with hemophilia: a report of low infection rates. J. Pediatr. 132, 934–938 (1998).

    Article  CAS  Google Scholar 

  39. Hevener, A. L., Bergman, R. N. & Donovan, C. M. Novel glucosensor for hypoglycemic detection localized to the portal vein. Diabetes 46, 1521–1525 (1997).

    Article  CAS  Google Scholar 

  40. Salgado, O. J., Urdaneta, B., Colmenares, B., García, R. & Flores, C. Right versus left internal jugular vein catheterization for hemodialysis: complications and impact on ipsilateral access creation. Artif. Organs 28, 728–733 (2004).

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported from National Research Foundation of South Korea (NRF) from the Ministry of Future Creative Science: Mid-Career Scientist Grant (2014002855) and End-Run Program funded by KAIST. In addition, this research was also supported from the Korea Health Technology R&D Project through the Health Industry Development Institute (KHIDI) and National R&D Program for Cancer Control by the Ministry of Health & Welfare, South Korea (HI14C2755; S.-W.K. and 1631060; H.L.).

Author information

Author notes

  1. Sun-Woong Kang and Haeshin Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. The Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

    Mikyung Shin & Haeshin Lee

  2. Predictive Model Research Center, Korea Institute of Toxicology (KIT), Daejeon 34114, Republic of Korea

    Sung-Gurl Park, Ki-Suk Kim & Sun-Woong Kang

  3. Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

    Byung-Chang Oh & Haeshin Lee

  4. R&D Center, InnoTherapy Inc., Seoul 07327, Republic of Korea

    Keumyeon Kim, Seongyeon Jo, Moon Sue Lee & Haeshin Lee

  5. Meta-Biomed Co., Cheongju, Chungbuk 28161, Republic of Korea

    Seok Song Oh

  6. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

    Seon-Hui Hong & Eui-Cheol Shin

  7. Department of Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Republic of Korea

    Ki-Suk Kim & Sun-Woong Kang

Authors
  1. Mikyung Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung-Gurl Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Byung-Chang Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keumyeon Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seongyeon Jo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Moon Sue Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seok Song Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Seon-Hui Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eui-Cheol Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ki-Suk Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sun-Woong Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Haeshin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.S. conceived and designed the experiments. M.S., S.-G.P. and B.-C.O. performed the experiments. S.J. prepared CHI-C. M.S. and B.-C.O. performed the preparation and the characterization of the haemostatic needles. M.S., S.-G.P. and K.K. performed in vivo experiments. M.S., S.-G.P., K.-S.K., S.-W.K. and H.L. interpreted in vivo results. M.S., K.K. and S.-H.H. performed HCV-related experiments. S.-H.H and E.-C.S. discussed and interpreted the viral infection results. M.S. and H.L. wrote the paper. All authors discussed the results. M.S. and H.L. supervised the project.

Corresponding authors

Correspondence to Sun-Woong Kang or Haeshin Lee.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1853 kb)

Supplementary Information

Supplementary movie 1 (MP4 1979 kb)

Supplementary Information

Supplementary movie 2 (MP4 1043 kb)

Supplementary Information

Supplementary movie 3 (MP4 4056 kb)

Supplementary Information

Supplementary movie 4 (MP4 6046 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shin, M., Park, SG., Oh, BC. et al. Complete prevention of blood loss with self-sealing haemostatic needles. Nature Mater 16, 147–152 (2017). https://doi.org/10.1038/nmat4758

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nmat4758

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing