Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells.
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.
Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
Xiaoyan
X
Ren
Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Daniel W
DW
Weisgerber
Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
David
D
Bischoff
Department of Pathology, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
Michael S
MS
Lewis
Section of Plastic and Reconstructive Surgery, University of Chicago, IL, 60637, USA.
Russell R
RR
Reid
Department of Orthopaedic Surgery, University of Chicago, Chicago, IL, 60637, USA.
Tong-Chuan
TC
He
Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
Dean T
DT
Yamaguchi
Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
Timothy A
TA
Miller
Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Brendan A C
BA
Harley
Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, 90095, USA.|Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, CA, 90073, USA.
Justine C
JC
Lee
D000943:Antigens, Differentiation / Q000096:biosynthesis; D002356:Cartilage / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects*; D003094:Collagen / Q000737:chemistry*; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*
D000943:Antigens, Differentiation; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D003094:Collagen
BMP9; biomimetic material; nanoparticulate mineralization; osteochondral regeneration