title: Gradients in pore size enhance the osteogenic differentiation of human mesenchymal stromal cells in three-dimensional scaffolds.
abstract: 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.
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5, 7522 NB, Enschede, The Nederlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Luca
authors.affiliation: Division of Materials Design, Faculty of Materials Science and Engineering, Warsaw University of Technology, 02-507, Warsaw, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ostrowska
authors.affiliation: Maastricht University, MERLN Institute for Technology Inspired Regenerative Medicine, Complex Tissue Regeneration department, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
authors.forename: Ivan
authors.initials: I
authors.lastname: Lorenzo-Moldero
authors.affiliation: Universita'di Sassari, Department of Biomedical Sciences, Via Muroni 25, Sassari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lepedda
authors.affiliation: Division of Materials Design, Faculty of Materials Science and Engineering, Warsaw University of Technology, 02-507, Warsaw, Poland.
authors.forename: Wojcech
authors.initials: W
authors.lastname: Swieszkowski
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5, 7522 NB, Enschede, The Nederlands.|Maastricht University, MERLN Institute for Technology Inspired Regenerative Medicine, Complex Tissue Regeneration department, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: Van Blitterswijk
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5, 7522 NB, Enschede, The Nederlands.|Maastricht University, MERLN Institute for Technology Inspired Regenerative Medicine, Complex Tissue Regeneration department, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase; D015519:Bone Density / Q000235:genetics; D001861:Bone Regeneration / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D050723:Fractures, Bone / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D000469:Alkaline Phosphatase