Ice‐Templated Protein Nanoridges Induce Bone Tissue Formation

Little is known about the role of biocompatible protein nanoridges in directing stem cell fate and tissue regeneration due to the difficulty in forming protein nanoridges. Here an ice-templating approach is proposed to produce semi-parallel pure silk protein nanoridges. The key to this approach is that water droplets formed in the protein films are frozen into ice crystals (removed later by sublimation), pushing the surrounding protein molecules to be assembled into nanoridges. Unlike the flat protein films, the unique protein nanoridges can induce the differentiation of human mesenchymal stem cells (MSCs) into osteoblasts without any additional inducers, as well as the formation of bone tissue in a subcutaneous rat model even when not seeded with MSCs. Moreover, the nanoridged films induce less inflammatory infiltration than the flat films in vivo. This work indicates that decorating biomaterials surfaces with protein nanoridges can enhance bone tissue formation in bone repair.