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Tissue Eng Regen Med. 2018 Sep 21;15(6):761-769. doi: 10.1007/s13770-018-0144-8. eCollection 2018 Dec.

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

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1Department of Biomedical Engineering, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul, 02841 Republic of Korea.
2Department of Mechanical Design Engineering, College of Engineering, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538 Republic of Korea.
3Department of Internal Medicine, Korea University Medical Center, 73 Inchon-ro, Seongbuk-gu, Seoul, 02841 Republic of Korea.



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.


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.


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.


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.


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

Conflict of interest statement

The authors have no financial conflict of interest.There are no animal experiments carried out for this article.

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