Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization

Greeshma Thrivikraman, Avathamsa Athirasala, Ryan Gordon, Limin Zhang, Raymond Bergan, Douglas R. Keene, James M. Jones, Hua Xie, Zhiqiang Chen, Jinhui Tao, Brian Wingender, Laurie Gower, Jack L. Ferracane and Luiz E. Bertassoni ()
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Greeshma Thrivikraman: Oregon Health and Science University
Avathamsa Athirasala: Oregon Health and Science University
Ryan Gordon: Oregon Health and Science University
Limin Zhang: Oregon Health and Science University
Raymond Bergan: Oregon Health and Science University
Douglas R. Keene: Shriners Hospital for Children
James M. Jones: Oregon Health and Science University
Hua Xie: Oregon Health and Science University
Zhiqiang Chen: Portland State University
Jinhui Tao: Pacific Northwest National Laboratory
Brian Wingender: University of Florida
Laurie Gower: University of Florida
Jack L. Ferracane: Oregon Health and Science University
Luiz E. Bertassoni: Oregon Health and Science University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Bone tissue, by definition, is an organic–inorganic nanocomposite, where metabolically active cells are embedded within a matrix that is heavily calcified on the nanoscale. Currently, there are no strategies that replicate these definitive characteristics of bone tissue. Here we describe a biomimetic approach where a supersaturated calcium and phosphate medium is used in combination with a non-collagenous protein analog to direct the deposition of nanoscale apatite, both in the intra- and extrafibrillar spaces of collagen embedded with osteoprogenitor, vascular, and neural cells. This process enables engineering of bone models replicating the key hallmarks of the bone cellular and extracellular microenvironment, including its protein-guided biomineralization, nanostructure, vasculature, innervation, inherent osteoinductive properties (without exogenous supplements), and cell-homing effects on bone-targeting diseases, such as prostate cancer. Ultimately, this approach enables fabrication of bone-like tissue models with high levels of biomimicry that may have broad implications for disease modeling, drug discovery, and regenerative engineering.

Date: 2019
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DOI: 10.1038/s41467-019-11455-8

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