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

  • Lee, Jaeyeon (Department of Biomedical Engineering, College of Medicine, Korea University) ;
  • Lee, Se-Hwan (Department of Mechanical Design Engineering, College of Engineering, Wonkwang University) ;
  • Kim, Byung Soo (Department of Internal Medicine, Korea University Medical Center) ;
  • Cho, Young-Sam (Department of Mechanical Design Engineering, College of Engineering, Wonkwang University) ;
  • Park, Yongdoo (Department of Biomedical Engineering, College of Medicine, Korea University)
  • Received : 2018.03.30
  • Accepted : 2018.07.10
  • Published : 2018.12.01

Abstract

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.

Keywords

Acknowledgement

Supported by : Ministry of Health and Welfare

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