Amino-Functionalized Mesoporous Silica Film as a Spatiotemporally Matched Degradable Nanotopography to Enhance Early Bioactivity and Osteogenesis on Titania Nanotube Surfaces

Nanotopographic fabrication has been proven to enhance the osteoinductivity of titanium implant surfaces; however, it is difficult for static nanostructures to regulate multiple osteoblast behaviors. Herein, we proposed a novel strategy for further modifying the nanostructured titanium surfaces using degradable nanotopography that was beneficial for specific cellular processes and spatiotemporally matched. In this work, a titania nanotube (TNT) array, known for its strong capability to promote osteogenic differentiation, was employed as the substrate. An oil-water biphase system containing 3-aminopropyl triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) was utilized to achieve the in situ deposition of amino-functionalized mesoporous silica films on the TNT surface (TNT@AHMS). The numerous mesopores (∼4 nm) and amino groups on AHMS significantly improved the protein adsorption and attachment of rat bone marrow mesenchymal stem cells (rBMSCs). By culturing in an AHMS-conditioned medium, the effects of AHMS in enhancing early cell behavior were observed and initially attributed to the potential synergism of the mesoporous topography and silicon element release (∼18 ppm). Impressively, this effect was maintained even when cells were reseeded on normal cell culture substrates. After 24 h, AHMS was degraded completely, and the degradation products further facilitated the subsequent osteogenic processes on re-exposed TNT, which accounted for robust osteogenesis both <i>in vitro</i> and <i>in vivo</i>. This study demonstrated that AHMS can serve as a degradable nanotopography (like a buffer layer) to accelerate protein adsorption and cell adhesion in a spatiotemporally matched manner, resulting in enhanced early bioactivity and osteogenesis for a well-designed underlying nanotopography without influencing its physicochemical properties.