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Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor

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Abstract

Cartilage tissue engineering is believed to provide effective cartilage repair post-injuries or diseases. Biomedical materials play a key role in achieving successful culture and fabrication of cartilage. The physical properties of a chitosan/gelatin hybrid hydrogel scaffold make it an ideal cartilage biomimetic material. In this study, a chitosan/gelatin hybrid hydrogel was chosen to fabricate a tissue-engineered cartilage in vitro by inoculating human adipose-derived stem cells (ADSCs) at both dynamic and traditional static culture conditions. A bioreactor that provides a dynamic culture condition has received greater applications in tissue engineering due to its optimal mass transfer efficiency and its ability to simulate an equivalent physical environment compared to human body. In this study, prior to cell-scaffold fabrication experiment, mathematical simulations were confirmed with a mass transfer of glucose and TGF-β2 both in rotating wall vessel bioreactor (RWVB) and static culture conditions in early stage of culture via computational fluid dynamic (CFD) method. To further investigate the feasibility of the mass transfer efficiency of the bioreactor, this RWVB was adopted to fabricate three-dimensional cell-hydrogel cartilage constructs in a dynamic environment. The results showed that the mass transfer efficiency of RWVB was faster in achieving a final equilibrium compared to culture in static culture conditions. ADSCs culturing in RWVB expanded three times more compared to that in static condition over 10 days. Induced cell cultivation in a dynamic RWVB showed extensive expression of extracellular matrix, while the cell distribution was found much more uniformly distributing with full infiltration of extracellular matrix inside the porous scaffold. The increased mass transfer efficiency of glucose and TGF-β2 from RWVB promoted cellular proliferation and chondrogenic differentiation of ADSCs inside chitosan/gelatin hybrid hydrogel scaffolds. The improved mass transfer also accelerated a dynamic fabrication of cell-hydrogel constructs, providing an alternative method in tissue engineering cartilage.

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Acknowledgments

This work was supported by the Fok Ying Tung Education Foundation (132027), National Natural Science Foundation of China (31370991/31170945/81301597), and Shenzhen Special Funds for the Emerging Strategic Industry Development (No. JCYJ20150525092940984), the State Key Laboratory of Fine Chemicals (KF1111), the Joint Open Foundation of Natural Science Foundation of Liaoning and Shenyang National Laboratory for Materials Science (2015021017) and the Fundamental Research Funds for the Central Universities (DUT14YQ106/DUT15QY47/16ZD210), and SRF for ROCS, SEM (42).

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Authors and Affiliations

  1. Shenzhen Key Laboratory for Anti-Ageing and Regenerative Medicine, Health Science Center, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, Guangdong, 518060, China

    Yanxia Zhu, Jinglian Chen, Lingzhi Tang & Siyuan Li

  2. State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian, 116024, China

    Yanxia Zhu, Kedong Song, Siyu Jiang, Jiangli Fan & Tianqing Liu

  3. Burns Research Group, ANZAC Research Institute, University of Sydney, Concord, NSW, 2139, Australia

    Yiwei Wang

  4. School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China

    Jiaquan Zhao

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  1. Yanxia Zhu
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  2. Kedong Song
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  3. Siyu Jiang
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  4. Jinglian Chen
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  7. Jiangli Fan
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  8. Yiwei Wang
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  9. Jiaquan Zhao
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  10. Tianqing Liu
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Corresponding authors

Correspondence to Kedong Song, Jiaquan Zhao or Tianqing Liu.

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Yanxia Zhu, Kedong Song, and Siyu Jiang are the co-first authors.

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Zhu, Y., Song, K., Jiang, S. et al. Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor. Appl Biochem Biotechnol 181, 250–266 (2017). https://doi.org/10.1007/s12010-016-2210-9

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