A novel 3D indirect co-culture system based on a collagen hydrogel scaffold for enhancing the osteogenesis of stem cells

Hyerim Kim, Shi Huan Han, Yun Min Kook, Kyung Mee Lee, Yuan Zhe Jin, Won Gun Koh, Jae Hyup Lee, Kangwon Lee

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


In this study, the paracrine effect between adipose-derived mesenchymal stem cells (ADSCs) and osteoblasts was investigated in collagen-based three-dimensional (3D) scaffolds. 3D encapsulation of mesenchymal stem cells in hydrogel scaffolds was conducted for bone tissue regeneration. Osteoblasts were encapsulated in alginate microbeads with uniform size, which could be controlled by varying the supply voltage using electrostatic droplet extrusion. Osteoblast-encapsulated microbeads were embedded with ADSCs in collagen bulk hydrogel scaffolds with a high survival rate. The separated space between the two types of cells made it possible to confirm ADSC differentiation into osteogenic lineages in the 3D collagen hydrogel scaffold by the paracrine effect in vitro. Furthermore, co-cultured ADSC and osteoblasts showed enhanced bone formation compared with the ADSC monoculture group in the rat calvarial defect model. The system developed in this study provides a novel in vitro tissue model for bone regeneration without exogenous factors, and it has the potential to be used to study the paracrine effect in various co-culture systems in the near future.

Original languageEnglish
Pages (from-to)9481-9491
Number of pages11
JournalJournal of Materials Chemistry B
Issue number41
Publication statusPublished - 2020 Nov 7

Bibliographical note

Funding Information:
This work was supported by the Collaborative Research Program of SNU Boramae Medical Center and Basic Medical Science from Seoul National University College of Medicine (800-20170005; J. H. Lee). This work was also supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3A9B4919711; K. Lee, and 2017M3A7B4041798 and 2018M3A9E2024583; W.-G. Koh). Lastly, this work was supported by NRF (National Research Foundation of Korea) Grant funded by the Korean Government (NRF-2017-Global PhD Fellowship Program; H. Kim).

Publisher Copyright:
© The Royal Society of Chemistry.

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)


Dive into the research topics of 'A novel 3D indirect co-culture system based on a collagen hydrogel scaffold for enhancing the osteogenesis of stem cells'. Together they form a unique fingerprint.

Cite this