Differential chondro- and osteo-stimulation in three-dimensional porous scaffolds with different topological surfaces provides a design strategy for biphasic osteochondral engineering

Abstract

Bone/cartilage interfacial tissue engineering needs to satisfy the differential properties and architectures of the osteochondral region. Therefore, biphasic or multiphasic scaffolds that aim to mimic the gradient hierarchy are widely used. Here, we find that two differently structured (topographically) three-dimensional scaffolds, namely, “dense” and “nanofibrous” surfaces, show differential stimulation in osteo- and chondro-responses of cells. While the nanofibrous scaffolds accelerate the osteogenesis of mesenchymal stem cells, the dense scaffolds are better in preserving the phenotypes of chondrocytes. Two types of porous scaffolds, generated by a salt-leaching method combined with a phase-separation process using the poly(lactic acid) composition, had a similar level of porosity (~90%) and pore size (~150 μm). The major difference in the surface nanostructure led to substantial changes in the surface area and water hydrophilicity (nanofibrous ≫ dense); as a result, the nanofibrous scaffolds increased the cell-to-matrix adhesion of mesenchymal stem cells significantly while decreasing the cell-to-cell contracts. Importantly, the chondrocytes, when cultured on nanofibrous scaffolds, were prone to lose their phenotype, including reduced chondrogenic expressions (SOX-9, collagen type II, and Aggrecan) and glycosaminoglycan content, which was ascribed to the enhanced cell–matrix adhesion with reduced cell–cell contacts. On the contrary, the osteogenesis of mesenchymal stem cells was significantly accelerated by the improved cell-to-matrix adhesion, as evidenced in the enhanced osteogenic expressions (RUNX2, bone sialoprotein, and osteopontin) and cellular mineralization. Based on these findings, we consider that the dense scaffold is preferentially used for the chondral-part, whereas the nanofibrous structure is suitable for osteo-part, to provide an optimal biphasic matrix environment for osteochondral tissue engineering.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…scaffolds ( Figure 3B). Interestingly, tailoring the surface topography of scaffolds by increasing either the roughness or the use of nano-scaled matrices has been shown to allow a better cell adhesion to the matrix, followed by subsequent tenogenic, osteogenic, and chondrogenic commitment of stem cells when in contact with oriented groove materials or just by creating dense or fibrous topologies in scaffolds, respectively [10,18,[44][45][46][47].…”

Biological Effects of Tricalcium Silicate Nanoparticle-Containing Cement on Stem Cells from Human Exfoliated Deciduous Teeth

“…Cell cytotoxicity was detected by the Cell Counting Kit-8 assay (CCK-8; Dojindo Laboratories, Kumamoto, Japan) [ 44 , 45 ]. Ten microliters of CCK-8 solution was added to each well, and the 96-well plates were placed in a CO 2 incubator for 1 h to react.…”

On the road to smart biomaterials for bone research: definitions, concepts, advances, and outlook

“…By contrast, the expression of chondrogenic markers SRY-Box Transcription Factor 9 (SOX-9), collagen type II (Col II), and Aggrecan was reduced when the cells were cultured on a nanofibrous PLDLA scaffold, even though these two scaffolds had similar porosities and pore sizes. 81 Increased surface area and hydrophilicity of the nanofibrous scaffold may have promoted cell-matrix adhesion while decreasing cell-cell contracts, while the nanofibrous scaffold promoted MSC osteogenic differentiation by enhancing the expression of runt-related transcription factor 2 (RUNX2), BSP, and OPN. 81 Mechanical properties (stiffness, storage modulus) Besides changing the basic structural properties of the scaffolds (such as morphology, topography, porosity, and pore size), manipulating substrate stiffness to mimic the natural 3D microenvironment will also impact osteogenic vs. chondrogenic fate decision.…”