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.
Statement of Significance
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.