Multifunctional and stable bone mimic proteinaceous matrix for bone tissue engineering

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.

Publication DOI: https://doi.org/10.1016/j.biomaterials.2015.03.022
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled 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
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Related URLs: https://www.sci ... 3002?via%3Dihub (Publisher URL)
PURE Output Type: Article
Published Date: 2015-07-01
Authors: Won, Jong-Eun
Yun, Ye-Rang
Jang, Jun-Hyeog
Yang, Sung-Hee
Kim, Joong-Hyun
Chrzanowski, Wojciech
Wall, Ivan B ( 0000-0001-6294-8348)
Knowles, Jonathan C
Kim, Hae-Won

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