Gradients in pore size enhance the osteogenic differentiation of human mesenchymal stromal cells in three-dimensional scaffolds

• Published in: Scientific reports 2016-03, Vol.6 (1), p.22898-22898, Article 22898
• Main Authors: Di Luca, Andrea, Ostrowska, Barbara, Lorenzo-Moldero, Ivan, Lepedda, Antonio, Swieszkowski, Wojcech, Van Blitterswijk, Clemens, Moroni, Lorenzo
• Format: Article
• Language: English
• Subjects: 13/100; 631/532/2118/2074; 639/301/54/2295; Adult; Aged; Alkaline Phosphatase; Bone density; Bone Density - genetics; Bone growth; Bone Regeneration - genetics; Bones; Calcium; Cancellous bone; Cell Differentiation - genetics; Cell Proliferation; Cells, Cultured; Cortical bone; Extracellular matrix; Female; Fractures; Fractures, Bone - pathology; Fractures, Bone - therapy; Humanities and Social Sciences; Humans; Male; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchyme; Mineralization; multidisciplinary; Osteogenesis - drug effects; Osteogenesis - genetics; Pore size; Porosity; Regeneration; Science; Science (multidisciplinary); Stem cells; Stromal cells; Tissue Engineering; Tissue Scaffolds
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22898

Small fractures in bone tissue can heal by themselves, but in case of larger defects current therapies are not completely successful due to several drawbacks. A possible strategy relies on the combination of additive manufactured polymeric scaffolds and human mesenchymal stromal cells (hMSCs). The architecture of bone tissue is characterized by a structural gradient. Long bones display a structural gradient in the radial direction, while flat bones in the axial direction. Such gradient presents a variation in bone density from the cancellous bone to the cortical bone. Therefore, scaffolds presenting a gradient in porosity could be ideal candidates to improve bone tissue regeneration. In this study, we present a construct with a discrete gradient in pore size and characterize its ability to further support the osteogenic differentiation of hMSCs. Furthermore, we studied the behaviour of hMSCs within the different compartments of the gradient scaffolds, showing a correlation between osteogenic differentiation and ECM mineralization, and pore dimensions. Alkaline phosphatase activity and calcium content increased with increasing pore dimensions. Our results indicate that designing structural porosity gradients may be an appealing strategy to support gradual osteogenic differentiation of adult stem cells.