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 Ferracane, Luiz Bertassoni

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number3520
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Biomimetics
biomimetics
collagens
bones
Bone
Collagen
Bone and Bones
Fabrication
fabrication
cells
Tissue
Cellular Microenvironment
Nanocomposites
Apatites
engineering
homing
Nanostructures
Bone Diseases
proteins
Biomineralization

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization. / Thrivikraman, Greeshma; Athirasala, Avathamsa; Gordon, Ryan; Zhang, Limin; Bergan, Raymond; Keene, Douglas R.; Jones, James M.; Xie, Hua; Chen, Zhiqiang; Tao, Jinhui; Wingender, Brian; Gower, Laurie; Ferracane, Jack; Bertassoni, Luiz.

In: Nature communications, Vol. 10, No. 1, 3520, 01.12.2019.

Research output: Contribution to journalArticle

Thrivikraman, Greeshma ; Athirasala, Avathamsa ; Gordon, Ryan ; Zhang, Limin ; Bergan, Raymond ; Keene, Douglas R. ; Jones, James M. ; Xie, Hua ; Chen, Zhiqiang ; Tao, Jinhui ; Wingender, Brian ; Gower, Laurie ; Ferracane, Jack ; Bertassoni, Luiz. / Rapid fabrication of vascularized and innervated cell-laden bone models with biomimetic intrafibrillar collagen mineralization. In: Nature communications. 2019 ; Vol. 10, No. 1.
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