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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.

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


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.


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

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