Scaffold channel size influences stem cell differentiation pathway in 3-D printed silica hybrid scaffolds for cartilage regeneration.

We report that 3-D printed scaffold channel size can direct bone marrow derived stem cell differentiation. Treatment of articular cartilage trauma injuries, such as microfracture surgery, have limited success because durability is limited as fibrocartilage forms. A scaffold-assisted approach, combining microfracture with biomaterials has potential if the scaffold can promote articular cartilage production and share load with cartilage. Here, we investigated human bone marrow derived stromal cell (hBMSC) differentiation in vitro in 3-D printed silica/poly(tetrahydrofuran)/poly(ε-caprolactone) hybrid scaffolds with specific channel sizes. Channel widths of ∼230 μm (210 ± 22 μm mean strut size, 42.4 ± 3.9% porosity) provoked hBMSC differentiation down a chondrogenic path, with collagen Type II matrix prevalent, indicative of hyaline cartilage. When pores were larger (∼500 μm, 229 ± 29 μm mean strut size, 63.8 ± 1.6% porosity) collagen Type I was dominant, indicating fibrocartilage. There was less matrix and voids in smaller channels (∼100 μm, 218 ± 28 μm mean strut size, 31.2 ± 2.9% porosity). Our findings suggest that a 200-250 μm pore channel width, in combination with the surface chemistry and stiffness of the scaffold, is optimal for cell-cell interactions to promote chondrogenic differentiation and enable the chondrocytes to maintain their phenotype.