Skip to main content
SpringerLink
Log in

Role of Free Catecholamine in Thiol-Ene Crosslinking for Hyaluronic Acid Hydrogels with High Loading Efficiency of Anticancer Drugs

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Hyaluronic acid (HA) is a widely used polysaccharide in biomedical field because of its excellent biocompatibility. Its chemical structure can be modified with various functional groups. Recently, dopamine has been tethered onto the polymeric backbone to ensure long-term stability and tissue adhesiveness of HA hydrogel. However, the radical scavenging effect of dopamine on typical photo-induced crosslinking for hydrogels has not been specifically studied.

Methods:

Photo-crosslinkable norbornene-modified HA (NorHA) was synthesized and crosslinked by dithiothreitol containing dopamine at different concentrations. During in situ ultraviolet light-triggered crosslinking, storage moduli were monitored using an oscillatory rheometer. Additionally, the amount of thiol utilized for HA crosslinking was investigated under the presence and absence of dopamine. Finally, doxorubicin was encapsulated in the hydrogels, and the drug loading efficiency and release kinetics were measured.

Results:

Adding dopamine into the NorHA pre-gel solution delayed the gelation time, yet the final storage modulus of the hydrogel remained constant. That is, dopamine might partially consume the energy required for thiol-ene reaction to generate semiquinone radicals. Furthermore, the residual thiols which were not involved in the crosslinking decreased when the hydrogel was formed at a high concentration of dopamine, indicating the formation of Michael adducts of semiquinone and thiols. Interestingly, the presence of dopamine in the hydrogel increased the loading efficiency of the hydrophobic drugs due to π-π stacking and hydrogen bonding between dopamine and drugs.

Conclusion:

The presence of free catecholamines in a photo-crosslinkable polymer can delay the gelation time but improve the drug loading efficiency.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Caló E, Khutoryanskiy VV. Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J. 2015;65:252–67.

    Article  Google Scholar 

  2. Choi JR, Yong KW, Choi JY, Cowie AC. Recent advances in photo-crosslinkable hydrogels for biomedical applications. Biotechniques. 2019;66:40–53.

    Article  CAS  Google Scholar 

  3. Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules. 2000;1:31–8.

    Article  Google Scholar 

  4. Hoch E, Schuh C, Hirth T, Tovar GE, Borchers K. Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation. J Mater Sci Mater Med. 2012;23:2607–17.

    Article  CAS  Google Scholar 

  5. Smeds KA, Pfister-Serres A, Miki D, Dastgheib K, Inoue M, Hatchell DL, et al. Photocrosslinkable polysaccharides for in situ hydrogel formation. J Biomed Mater Res. 2001;54:115–21.

    Article  CAS  Google Scholar 

  6. Gramlich WM, Kim IL, Burdick JA. Synthesis and orthogonal photopatterning of hyaluronic acid hydrogels with thiol-norbornene chemistry. Biomaterials. 2013;34:9803–11.

    Article  CAS  Google Scholar 

  7. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242:27–33.

    Article  CAS  Google Scholar 

  8. Burdick JA, Prestwich GD. Hyaluronic acid hydrogels for biomedical applications. Adv Mater. 2011;23:H41–56.

    Article  CAS  Google Scholar 

  9. Rodell CB, Kaminski AL, Burdick JA. Rational design of network properties in guest–host assembled and shear-thinning hyaluronic acid hydrogels. Biomacromolecules. 2013;14:4125–34.

    Article  CAS  Google Scholar 

  10. Highley CB, Rodell CB, Burdick JA. Direct 3D printing of shear-thinning hydrogels into self-healing hydrogels. Adv Mater. 2015;27:5075–9.

    Article  CAS  Google Scholar 

  11. Shin M, Lee H. Gallol-rich hyaluronic acid hydrogels: shear-thinning, protein accumulation against concentration gradients, and degradation-resistant properties. Chem Mater. 2017;29:8211–20.

    Article  CAS  Google Scholar 

  12. Lee H, Lee Y, Statz AR, Rho J, Park TG, Messersmith PB. Substrate-independent layer-by-layer assembly by using mussel-adhesive-inspired polymers. Adv Mater. 2008;20:1619–23.

    Article  CAS  Google Scholar 

  13. Zhang K, Wei Z, Xu X, Feng Q, Xu J, Bian L. Efficient catechol functionalization of biopolymeric hydrogels for effective multiscale bioadhesion. Mater Sci Eng C Mater Biol Appl. 2019;103:109835.

    Article  CAS  Google Scholar 

  14. Zhan K, Kim C, Sung K, Ejima H, Yoshie N. Tunicate-inspired gallol polymers for underwater adhesive: a comparative study of catechol and gallol. Biomacromolecules. 2017;18:2959–66.

    Article  CAS  Google Scholar 

  15. Zeng C, Villar VA, Yu P, Zhou L, Jose PA. Reactive oxygen species and dopamine receptor function in essential hypertension. Clin Exp Hypertens. 2009;31:156–78.

    Article  CAS  Google Scholar 

  16. Kim BG, Kim S, Lee H, Choi JW. Wisdom from the human eye: a synthetic melanin radical scavenger for improved cycle life of Li–O2 battery. Chem Mater. 2014;26:4757–64.

    Article  CAS  Google Scholar 

  17. Lee K, Tiu BDB, Martchenko V, Mai K, Lee G, Gerst M, et al. A modular strategy for functional pressure sensitive adhesives. ACS Appl Mater Interfaces. 2021;13:3161–5.

    Article  CAS  Google Scholar 

  18. Wang Y, Wu Y, Li K, Shen S, Liu Z, Wu D. Ultralong circulating lollipop-like nanoparticles assembled with Gossypol, Doxorubicin, and Polydopamine via π–π stacking for synergistic tumor therapy. Adv Funct Mater. 2019;29:1805582.

    Article  Google Scholar 

  19. Di Meo F, Lemaur V, Cornil J, Lazzaroni R, Duroux JL, Olivier Y, et al. Free radical scavenging by natural polyphenols: atom versus electron transfer. J Phys Chem A. 2013;117:2082–92.

    Article  Google Scholar 

  20. Lee BP, Messersmith PB, Israelachvili JN, Waite JH. Mussel-inspired adhesives and coatings. Annu Rev Mater Res. 2011;41:99–132.

    Article  CAS  Google Scholar 

  21. Faure E, Falentin-Daudré C, Jérôme C, Lyskawa J, Fournier D, Woisel P, et al. Catechols as versatile platforms in polymer chemistry. Prog Polym Sci. 2013;38:236–70.

    Article  CAS  Google Scholar 

  22. Sedó J, Saiz-Poseu J, Busqué F, Ruiz-Molina D. Catechol-based biomimetic functional materials. Adv Mater. 2013;25:653–701.

    Article  Google Scholar 

  23. Aitken A, Learmonth M. Estimation of disulfide bonds using Ellman’s reagent. In: Walker JM, editor. The protein protocols handbook. Totowa: Humana Press; 1996. p. 487–8.

    Chapter  Google Scholar 

  24. Lee H, Dellatore SM, Miller WM, Messersmith PB. Mussel-inspired surface chemistry for multifunctional coatings. Science. 2007;318:426–30.

    Article  CAS  Google Scholar 

  25. Nieto C, Vega MA, Enrique J, Marcelo G, Martín del Valle EM. Size matters in the cytotoxicity of polydopamine nanoparticles in different types of tumors. Cancers (Basel). 2019;11:1679.

    Article  CAS  Google Scholar 

  26. Ambekar RS, Kandasubramanian B. A polydopamine-based platform for anti-cancer drug delivery. Biomater Sci. 2019;7:1776–93.

    Article  CAS  Google Scholar 

  27. Mousavi S, Zarei M, Hashemi S. Polydopamine for biomedical application and drug delivery system. Med Chem (Los Angeles). 2018;8:218–29.

    Google Scholar 

  28. Liu M, Zeng G, Wang K, Wan Q, Tao L, Zhang X, et al. Recent developments in polydopamine: an emerging soft matter for surface modification and biomedical applications. Nanoscale. 2016;8:16819–40.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by the Ministry of Health and Welfare, Republic of Korea, and National Research Foundation of Korea (NRF) through a Grant funded by the Korean government (MSIT) (NRF-2020R1C1C1003903) and the Korea Medical Device Development Fund Grant funded by the Korean government (Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health & Welfare, Ministry of Food and Drug Safety) (202012D28).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea

    Sumin Kim & Mikyung Shin

  2. Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea

    Sumin Kim & Mikyung Shin

Authors
  1. Sumin Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mikyung Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mikyung Shin.

Ethics declarations

Conflict of interest

The authors have declared that they have no conflict of interest.

Ethical Statement

There are no animal experiments carried out for this article.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 789 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, S., Shin, M. Role of Free Catecholamine in Thiol-Ene Crosslinking for Hyaluronic Acid Hydrogels with High Loading Efficiency of Anticancer Drugs. Tissue Eng Regen Med 19, 281–287 (2022). https://doi.org/10.1007/s13770-021-00388-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-021-00388-3

Keywords

Search

Navigation