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Nanoparticulate Mineralized Collagen Scaffolds and BMP‐9 Induce a Long‐Term Bone Cartilage Construct in Human Mesenchymal Stem Cells
Author(s) -
Ren Xiaoyan,
Weisgerber Daniel W.,
Bischoff David,
Lewis Michael S.,
Reid Russell R.,
He TongChuan,
Yamaguchi Dean T.,
Miller Timothy A.,
Harley Brendan A. C.,
Lee Justine C.
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600187
Subject(s) - chondrogenesis , mesenchymal stem cell , microbiology and biotechnology , aggrecan , chemistry , bone morphogenetic protein 2 , glycosaminoglycan , alkaline phosphatase , cartilage , extracellular matrix , osteopontin , chondrocyte , scaffold , biomedical engineering , anatomy , immunology , biochemistry , biology , osteoarthritis , pathology , medicine , in vitro , articular cartilage , enzyme , alternative medicine
Engineering the osteochondral junction requires fabrication of a microenvironment that supports both osteogenesis and chondrogenesis. Multiphasic scaffold strategies utilizing a combination of soluble factors and extracellular matrix components are ideally suited for such applications. In this work, the contribution of an osteogenic nanoparticulate mineralized glycosaminoglycan scaffold (MC‐GAG) and a dually chondrogenic and osteogenic growth factor, BMP‐9, in the differentiation of primary human mesenchymal stem cells (hMSCs) is evaluated. Although 2D cultures demonstrate alkaline phosphatase activity and mineralization of hMSCs induced by BMP‐9, MC‐GAG scaffolds do not demonstrate significant differences in the collagen I expression, osteopontin expression, or mineralization. Instead, BMP‐9 increases expression of collagen II, Sox9, aggrecan (ACAN), and cartilage oligomeric protein. However, the hypertrophic chondrocyte marker, collagen X, is not elevated with BMP‐9 treatment. In addition, histologic analyses demonstrate that while BMP‐9 does not increase mineralization, BMP‐9 treatment results in an increase of sulfated glycosaminoglycans. Thus, the combination of BMP‐9 and MC‐GAG stimulates chondrocytic and osteogenic differentiation of hMSCs.