Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk-Silica Chimeras

Biomineralization at the organic-inorganic interface is critical to many biology material functions in vitro and in vivo. Recombinant silk-silica fusion peptides are organic-inorganic hybrid material systems that can be effectively used to study and control biologically mediated mineralization due to the genetic basis of sequence control. However, to date, the mechanisms by which these functionalized silk-silica proteins trigger the differentiation of human mesenchymal stem cells (hMSCs) to osteoblasts remain unknown. To address this challenge, silk-silica surfaces are analyzed for silica-hMSC receptor binding and activation, and the intracellular pathways involved in the induction of osteogenesis on these bioengineered biomaterials. The induction of gene expression of alpha V beta 3 integrin, all three mitogen-activated protein kinsases, as well as c-Jun, runt-related transcription factor 2, and osteoblast marker genes is demonstrated upon growth of the hMSCs on the silk-silica materials. This induction of key markers of osteogenesis correlates with the content of silica on the materials. Moreover, computational simulations are performed for silk/silica-integrin binding which show activation of alpha V beta 3 integrin in contact with silica. This integrated computational and experimental approach provides insight into interactions that regulate osteogenesis toward more efficient biomaterial designs.