Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells

Adv Healthc Mater. 2016 Jul;5(14):1821-30. doi: 10.1002/adhm.201600187. Epub 2016 Jun 8.

Abstract

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.

Keywords: BMP9; biomimetic material; nanoparticulate mineralization; osteochondral regeneration.

MeSH terms

  • Antigens, Differentiation / biosynthesis
  • Cartilage / metabolism
  • Chondrogenesis / drug effects*
  • Collagen / chemistry*
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors* / chemistry
  • Growth Differentiation Factors* / pharmacology
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Nanoparticles / chemistry*
  • Osteogenesis / drug effects*
  • Tissue Scaffolds / chemistry*

Substances

  • Antigens, Differentiation
  • GDF2 protein, human
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors
  • Collagen