Microtopography “not” macrostructure affects the osteogenic differentiation of human mesenchymal stem cells through RHOA and LATS1

Abstract

Three-dimensional (3D) biomaterials provide a tridimensional living environment for human mesenchymal stem cells (hMSC). However, the regulation mechanism of biomaterials’ macro and micro structure on cell differentiation is not clear. Here, we used selective laser melting (SLM) technology to fabricate 3D biomaterials with different macro and micro structure characteristics. Results showed that the different morphology of hMSCs is not the determinant of their differentiation stat, which might be influenced by the macrostructure of biomaterials. And the effect of microstructure of the biomaterial on osteogenic differentiation of hMSCs was more remarkable than that of the macrostructure ones. The microstructure affected the nuclear localization of Yes-associated protein (YAP) by interfering with the balance between Ras homolog gene family member A (RHOA) and large tumor suppressor 1 (LATS1), thereby influencing the osteogenic differentiation of hMSCs. Precise gene knockout experiments also proved that the mediation of the development and regeneration of cranial bones in mice was caused by the balance of RHOA and LATS1. In addition, we used SLM to fabricate titanium-based implant surface with microstructures to achieve better bone regeneration and implant osseointegration.