Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering

Jong-Eun Won, Ye-Rang Yun, Jun-Hyeog Jang, Sung-Hee Yang, Joong-Hyun Kim, Wojciech Chrzanowski, Ivan B Wall, Jonathan C Knowles, Hae-Won Kim

Research output: Contribution to journalArticle

Abstract

Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

Original languageEnglish
Pages (from-to)46-57
Number of pages12
JournalBiomaterials
Volume56
DOIs
Publication statusPublished - 1 Jul 2015

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Tissue Engineering
Tissue engineering
Bone
Bone and Bones
Stem cells
Collagen
Osteogenesis
Fibrillar Collagens
Biomimetics
Bone Matrix
Osteocalcin
Proteins
Fibronectins
Extracellular Matrix
Stem Cells
Biopolymers
Bone Regeneration
Focal Adhesions
Cell adhesion
Biocompatible Materials

Bibliographical note

© 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • Animals
  • Biocompatible Materials/chemistry
  • Biopolymers/chemistry
  • Bone Regeneration
  • Bone and Bones/pathology
  • Cell Adhesion
  • Cell Differentiation
  • Cell Proliferation
  • Collagen/chemistry
  • Fibronectins/chemistry
  • Male
  • Mesenchymal Stem Cells/cytology
  • Osteocalcin/chemistry
  • Osteogenesis
  • Phenotype
  • Protein Engineering/methods
  • Protein Structure, Secondary
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins/chemistry
  • Surface Properties
  • Tissue Engineering/methods
  • Tissue Scaffolds/chemistry

Cite this

Won, J-E., Yun, Y-R., Jang, J-H., Yang, S-H., Kim, J-H., Chrzanowski, W., ... Kim, H-W. (2015). Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering. Biomaterials, 56, 46-57. https://doi.org/10.1016/j.biomaterials.2015.03.022
Won, Jong-Eun ; Yun, Ye-Rang ; Jang, Jun-Hyeog ; Yang, Sung-Hee ; Kim, Joong-Hyun ; Chrzanowski, Wojciech ; Wall, Ivan B ; Knowles, Jonathan C ; Kim, Hae-Won. / Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering. In: Biomaterials. 2015 ; Vol. 56. pp. 46-57.
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Won, J-E, Yun, Y-R, Jang, J-H, Yang, S-H, Kim, J-H, Chrzanowski, W, Wall, IB, Knowles, JC & Kim, H-W 2015, 'Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering', Biomaterials, vol. 56, pp. 46-57. https://doi.org/10.1016/j.biomaterials.2015.03.022

Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering. / Won, Jong-Eun; Yun, Ye-Rang; Jang, Jun-Hyeog; Yang, Sung-Hee; Kim, Joong-Hyun; Chrzanowski, Wojciech; Wall, Ivan B; Knowles, Jonathan C; Kim, Hae-Won.

In: Biomaterials, Vol. 56, 01.07.2015, p. 46-57.

Research output: Contribution to journalArticle

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T1 - Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering

AU - Won, Jong-Eun

AU - Yun, Ye-Rang

AU - Jang, Jun-Hyeog

AU - Yang, Sung-Hee

AU - Kim, Joong-Hyun

AU - Chrzanowski, Wojciech

AU - Wall, Ivan B

AU - Knowles, Jonathan C

AU - Kim, Hae-Won

N1 - © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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N2 - Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.

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KW - Fibronectins/chemistry

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KW - Rats

KW - Rats, Sprague-Dawley

KW - Recombinant Fusion Proteins/chemistry

KW - Surface Properties

KW - Tissue Engineering/methods

KW - Tissue Scaffolds/chemistry

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