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Acta Biomater. 2016 Jan;29:42-51. doi: 10.1016/j.actbio.2015.10.039. Epub 2015 Oct 24.

Mineral particles modulate osteo-chondrogenic differentiation of embryonic stem cell aggregates.

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Gladstone Institute of Cardiovascular Disease, The Gladstone Institutes, San Francisco, CA 94158, USA.
Departments of Biomedical Engineering & Orthopedics and Rehabilitation, University of Wisconsin-Madison, Madison, WI 53705, USA.
The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Gladstone Institute of Cardiovascular Disease, The Gladstone Institutes, San Francisco, CA 94158, USA; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA. Electronic address:


Pluripotent stem cell aggregates offer an attractive approach to emulate embryonic morphogenesis and skeletal development. Calcium phosphate (CaP) based biomaterials have been shown to promote bone healing due to their osteoconductive and potential osteoinductive properties. In this study, we hypothesized that incorporation of CaP-coated hydroxyapatite mineral particles (MPs) within murine embryonic stem cell (ESC) aggregates could promote osteo-chondrogenic differentiation. Our results demonstrated that MP alone dose-dependently promoted the gene expression of chondrogenic and early osteogenic markers. In combination with soluble osteoinductive cues, MPs enhanced the hypertrophic and osteogenic phenotype, and mineralization of ESC aggregates. Additionally, MPs dose-dependently reduced ESC pluripotency and thereby decreased the size of teratomas derived from MP-incorporated ESC aggregates in vivo. Our data suggested a novel yet simple means of using mineral particles to control stem cell fate and create an osteochondral niche for skeletal tissue engineering applications.


Directing stem cell differentiation and morphogenesis via biomaterials represents a novel strategy to promote cell fates and tissue formation. Our study demonstrates the ability of calcium phosphate-based mineral particles to promote osteochondrogenic differentiation of embryonic stem cell aggregates as well as modulate teratoma formation in vivo. This hybrid biomaterial-ESC aggregate approach serves as an enabling platform to evaluate the ability of biomaterials to regulate stem cell fate and regenerate functional skeletal tissues for clinical applications.


Differentiation; Embryonic stem cells; Mineral microparticles; Osteo-chondrogenesis

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