Theranostics 2015; 5(6):643-655. doi:10.7150/thno.11372 This issue

Research Paper

3D Porous Calcium-Alginate Scaffolds Cell Culture System Improved Human Osteoblast Cell Clusters for Cell Therapy

Ching-Yun Chen1, Cherng-Jyh Ke2,3, Ko-Chung Yen1, Hui-Chen Hsieh1, Jui-Sheng Sun3,4,5,6*✉, Feng-Huei Lin1,7*✉

1. Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan (R.O.C.).
2. Biomaterials Translational Research Center, China Medical University Hospital, Taichung, Taiwan (R.O.C.).
3. Department of Biomedical Electronics Translational Research Center and Biomimetic Systems Research Center, National Chiao Tung University, Hsinchu, Taiwan (R.O.C.).
4. Department of Orthopedics, College of Medicine, National Taiwan University, Taipei, Taiwan (R.O.C.).
5. Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan (R.O.C.).
6. Department of Orthopedic Surgery, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan (R.O.C.).
7. Institute of Biomedical Engineering and Nanomedicine (I-BEN), National Health Research Institutes, Miaoli, Taiwan (R.O.C.).
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Chen CY, Ke CJ, Yen KC, Hsieh HC, Sun JS, Lin FH. 3D Porous Calcium-Alginate Scaffolds Cell Culture System Improved Human Osteoblast Cell Clusters for Cell Therapy. Theranostics 2015; 5(6):643-655. doi:10.7150/thno.11372. Available from

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Graphic abstract

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.

Keywords: Three-dimensional culture, Preformed scaffolds, Bone-like tissues, Perfusion, Autografts