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

Nature Communications
Greeshma ThrivikramanLuiz E Bertassoni

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.

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Citations

Feb 25, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xinyuan XuJianshu Li
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Methods Mentioned

BETA
X-ray
electron diffraction
infrared spectroscopy
atomic force microscopy
confocal microscopy
AFM
electron tomography
PCR
enzyme-linked immunosorbent
chip

Software Mentioned

Primer
FEI Tomography
Amira Animation Director
AngioTool
ImageJ
Amira
Imaris Filament Tracer
GraphPad
ZEN black
Prism5

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