This study investigated the osteogenesis-related cell functions of osteoprogenitor cells modulated by surface chemistry modification using lithium (Li) ions in a current clinical oral implant surface in order to gain insights into the future development of titanium (Ti) implants with enhanced osteogenic capacity. Wet chemical treatment was performed to modify a sandblasted/acid-etched (SLA) Ti implant surface using Li ions. The osteogenesis-related cell response to the surface Li ion-modified SLA sample was evaluated using two kinds of murine bone marrow stem cells, bipotent ST2 cells and primary multipotent mesenchymal stem cells (MSCs). The modified surface exhibited the formation of an Li-containing Ti oxide layer with plate-like nanostructures. The Li-incorporated surface enhanced early cellular events, including spreading, focal adhesion formation and integrin mRNA expression (α2, α5, αv and β3), and accelerated osteogenic differentiation of bipotent ST2 cells compared with unmodified SLA surface. Surface Li modification significantly increased GSK-3β phosphorylation and suppressed β-catenin phosphorylation, and promoted the subsequent osteogenic differentiation of primary MSCs. These results indicate that surface chemistry modification of SLA implants by wet chemical treatment with Li ions induces a more favorable osseointegration outcome through the promotion of the osteogenic differentiation of bone marrow MSCs via the positive regulation of GSK-3β and β-catenin activity.
Keywords: Titanium implants; glycogen synthase kinase 3β; lithium; mesenchymal stem cells; osteogenic differentiation; surface modifications.