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Adv Healthc Mater. 2015 Oct 28;4(15):2306-13. doi: 10.1002/adhm.201500598. Epub 2015 Sep 15.

Spatially organized differentiation of mesenchymal stem cells within biphasic microparticle-incorporated high cell density osteochondral tissues.

Author information

1
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.
2
Departments of Biomedical Engineering and Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI, 53706, USA.
3
AO Foundation Collaborative Research Center, Clavadelerstrasse 8, Davos, 7270, Switzerland.
4
Department of Orthopaedic Surgery, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH, 44106, USA.

Abstract

Giving rise to both bone and cartilage during development, bone marrow-derived mesenchymal stem cells (hMSC) have the unique capacity to generate the complex tissues of the osteochondral interface. Utilizing a scaffold-free hMSC system, biphasic osteochondral constructs are incorporated with two types of growth factor-releasing microparticles to enable spatially organized differentiation. Gelatin microspheres (GM) releasing transforming growth factor-β1 (TGF-β1) combined with hMSC form the chondrogenic phase. The osteogenic phase contains hMSC only, mineral-coated hydroxyapatite microparticles (MCM), or MCM loaded with bone morphogenetic protein-2 (BMP-2), cultured in medium with or without BMP-2. After 4 weeks, TGF-β1 release from GM within the cartilage phase promotes formation of a glycosaminoglycan- and type II collagen-rich matrix, and has a local inhibitory effect on osteogenesis. In the osteogenic phase, type X collagen and osteopontin are produced in all conditions. However, calcification occurs on the outer edges of the chondrogenic phase in some constructs cultured in media containing BMP-2, and alkaline phosphatase levels are elevated, indicating that BMP-2 releasing MCM provides better control over region-specific differentiation. The production of complex, stem cell-derived osteochondral tissues via incorporated microparticles could enable earlier implantation, potentially improving outcomes in the treatment of osteochondral defects.

KEYWORDS:

BMP (bone morphogenetic protein); TGF (transforming growth factor); bone; cartilage; hydroxyapatite

PMID:
26371790
PMCID:
PMC4638379
DOI:
10.1002/adhm.201500598
[Indexed for MEDLINE]
Free PMC Article

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