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Study on the potential of RGD- and PHSRN-modified alginates as artificial extracellular matrices for engineering bone

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Abstract

Alginate is a polysaccharide that can be crosslinked by divalent cations, such as calcium ions, to form a gel. Chemical modification is typically used to improve its cell adhesive properties for tissue engineering applications. In this study, alginates were modified with peptides containing RGD (arginine–glycine–aspartic acid) or PHSRN (proline–histidine–serine–arginine–asparagine) sequences from fibronectin to study possible additive and synergistic effects on adherent cells. Alginates modified with each peptide were mixed at different ratios to form gels containing various concentrations and spacing between the RGD and PHSRN sequences. When normal human osteoblasts (NHOsts) were cultured on or in the gels, the ratio of RGD to PHSRN was found to influence cell behaviors, especially differentiation. NHOsts cultured on gels composed of RGD- and PHSRN-modified alginates showed enhanced differentiation when the gels contained >33 % RGD-alginate, suggesting the relative distribution of the peptides and the presentation to cells are important parameters in this regulation. NHOsts cultured in gels containing both RGD- and PHSRN-alginates also demonstrated a similar enhancement tendency of calcium deposition that was dependent on the peptide ratio in the gel. However, calcium deposition was greater when cells were cultured in the gels, as compared to on the gels. These results suggest that modifying this biomaterial to more closely mimic the chemistry of natural cell adhesive proteins, (e.g., fibronectin) may be useful in developing scaffolds for bone tissue engineering and provide three-dimensional cell culture systems which more closely mimic the environment of the human body.

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Acknowledgments

This work was partly supported by Health and Labour Sciences Research Grants for Research on Regulatory Science of Pharmaceuticals and Medical Devices by Ministry of Health, Labour and Welfare (H24-Iyaku-Shitei-018). The authors are also grateful to Dr. Kuen Yong Lee (Hanyang University, South Korea), Dr. Hyun-Joon Kong (University of Illinois, USA), and Dr. Takuya Matsumoto (Okayama University, Japan) for many helpful discussions.

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Author notes

  1. Toshie Tsuchiya

    Present address: Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

Authors and Affiliations

  1. Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Ryusuke Nakaoka, Toshie Tsuchiya & Atsuko Matsuoka

  2. Department of Chemistry and Material Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate, Suita-shi, Osaka, 564-8680, Japan

    Yoshiaki Hirano

  3. School of Engineering and Applied Sciences, Harvard University, Pierce Hall 319, 29 Oxford Street, Cambridge, MA, 02138, USA

    David J. Mooney

Authors
  1. Ryusuke Nakaoka
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  2. Yoshiaki Hirano
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  3. David J. Mooney
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  4. Toshie Tsuchiya
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  5. Atsuko Matsuoka
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Correspondence to Ryusuke Nakaoka or Atsuko Matsuoka.

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Nakaoka, R., Hirano, Y., Mooney, D.J. et al. Study on the potential of RGD- and PHSRN-modified alginates as artificial extracellular matrices for engineering bone. J Artif Organs 16, 284–293 (2013). https://doi.org/10.1007/s10047-013-0703-7

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  • DOI: https://doi.org/10.1007/s10047-013-0703-7

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