title: Influencing chondrogenic differentiation of human mesenchymal stromal cells in scaffolds displaying a structural gradient in pore size.
abstract: Articular cartilage lesions have a limited ability to heal by themselves. Yet, golden standard treatments for cartilage repair such as drilling, microfracture and mosaicplasty provide further damage and an unstable solution that degenerates into fibrocartilage in time. Articular cartilage presents a number of gradients in cell number and size along with structural gradients in extra cellular matrix (ECM) composition. Therefore, creating scaffolds that display a structural gradient can be an appealing strategy for cartilage tissue regeneration treatments. In the present study, a scaffold with an in-built discrete gradient in pore size was produced by additive manufacturing. Human mesenchymal stromal cells (hMSCs) were seeded within the gradient scaffolds and their proliferation, differentiation and ECM deposition was evaluated with respect to 2 non-gradient scaffolds. Glycosaminoglycan (GAG) deposition was significantly higher in gradient scaffolds and non-gradient scaffolds with the smallest pore size compared to non-gradient scaffolds with the largest pore size. A gradual increase of chondrogenic markers was observed within the gradient structures with decreasing pore size, which was also accompanied by an increasingly compact ECM formation. Therefore, scaffolds displaying a structural gradient in pore size seem to be a promising strategy to aid in the process of hMSC chondrogenic differentiation and could be considered for improved cartilage tissue regeneration applications.
  
  
  
  We present the development of a novel hierarchical scaffold obtained by additive manufacturing. Structural hierarchy is obtained by changing pore size within the pore network characterizing the fabricated scaffolds and proves to be a functional element in the scaffold to influence adult stem cell differentiation in the chondrogenic lineage. Specifically, in regions of the scaffolds presenting smaller pores an increasing differentiation of stem cells toward the chondrogenic differentiation is displayed. Taking inspiration from the zonal organization of articular cartilage tissue, pore size gradients could, therefore, be considered as a new and important element in designing 3D scaffolds for regenerative medicine applications, in particular for all those tissues where gradient physical properties are present.
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Luca
authors.affiliation: Materials Design Division, Faculty of Material Science and Engineering, Warsaw University of Technology, 141 Woloska Street, 02-507 Warsaw, Poland.
authors.forename: Karol
authors.initials: K
authors.lastname: Szlazak
authors.affiliation: University of Twente, Tissue Regeneration Department, Drienerlolaan 5, 7522 NB Enschede, The Netherlands; 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: University of Twente, Developmental Bio-engineering Department, Drienerlolaan 5, 7522 NB Enschede, The Netherlands.
authors.forename: Corina A
authors.initials: CA
authors.lastname: Ghebes
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: Materials Design Division, Faculty of Material Science and Engineering, Warsaw University of Technology, 141 Woloska Street, 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 Netherlands; 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 Netherlands; Maastricht University, MERLN Institute for Technology Inspired Regenerative Medicine, Complex Tissue Regeneration Department, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. Electronic address: l.moroni@maastrichtuniversity.nl.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moroni
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D016062:Porosity; D054457:Tissue Scaffolds / Q000737:chemistry*
keywords: 3D scaffolds; Additive manufacturing; Gradients; Stem cells