We demonstrate that imparting freeform fabricated (FFF) scaffolds with surface roughness on their struts enhances osteogenic differentiation of primary human bone marrow stromal cells (hBMSCs) by controlling cell shape. Previous work showed that hBMSCs underwent rapid proliferation without osteogenic differentiation during culture in FFF scaffolds. In contrast, hBMSCs underwent osteogenic differentiation with slow proliferation during culture in nanofiber scaffolds. Herein, we hypothesized that combining the open pore structure of FFF scaffolds with surface roughness of nanofiber scaffolds would yield hybrid scaffolds that both supported proliferation and drove osteogenesis to generate a maximum amount of bone-like tissue. A solvent etching method was developed that imparted a 5-fold increase in roughness on the surface of poly(-caprolactone) FFF scaffold struts. Etched scaffolds induced osteogenic differentiation of the hBMSCs while un-etched scaffolds did not. The etched scaffolds also supported the same high levels of hBMSC proliferation that un-etched scaffolds supported. Finally, hBMSCs on un-etched scaffolds had a large spread area while hBMSCs on etched scaffolds has a smaller area and were more rounded indicating that the surface roughness from the etched scaffolds affected hBMSC morphology. The results demonstrate that FFF scaffolds with surface roughness can support hBMSC proliferation while also inducing osteogenic differentiation to maximize generation of calcified, bone-like tissue. This work also validates a rational approach to scaffold fabrication where the structure of the scaffold was designed to modulate stem cell function by controlling stem cell morphology.
Pub Type: Journals
cell proliferation, cell spreading, osteogenesis, scaffold, surface topography, stem cell, osteoprogenitor cells