Development and Evaluation of Hyaluronic Acid-Based Hybrid Bio-Ink for Tissue Regeneration

Jaeyeon Lee, Se Hwan Lee, Byung Soo Kim, Young Sam Cho, Yongdoo Park

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Background:: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. Methods:: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bio-active peptides and tyramine-conjugated hyaluronic acids for fast gelation. Results:: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bio-ink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed > 90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. Conclusion:: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.

Original languageEnglish
Pages (from-to)761-769
Number of pages9
JournalTissue Engineering and Regenerative Medicine
Issue number6
Publication statusPublished - 2018 Dec 1

Bibliographical note

Funding Information:
Acknowledgement This study was supported by a grant from the Ministry of Health and Welfare in the Republic of Korea (HI14C2143).

Publisher Copyright:
© 2018, The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature.


  • Bio-ink
  • Bioprinting
  • Hyaluronic acid
  • Hydrogel
  • Tissue engineering

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomedical Engineering


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