Natural silk nanofibers as building blocks for biomimetic aerogel scaffolds

Protein nanofibers offer great promise for tissue engineering scaffolds owing to biomimetic architecture and exceptional biocompatibility. Natural silk nanofibrils (SNFs) are promising but unexplored protein nanofibers for biomedical applications. In this study, the SNF-assembled aerogel scaffolds with ECM-mimicking architecture and ultra-high porosity are developed based on a polysaccharides-assisted strategy. The SNFs exfoliated from silkworm silks can be utilized as building blocks to construct 3D nanofibrous scaffolds with tunable densities and desirable shapes on a large scale. We demonstrate that the natural polysaccharides can regulate SNF assembly through multiple binding modes, endowing the scaffolds with structural stability in water and tunable mechanical properties. As a proof of concept, the biocompatibility and biofunctionality of the chitosan-assembled SNF aerogels were investigated. The nanofibrous aerogels have excellent biocompatibility, and their biomimetic structure, ultra-high porosity, and large specific surface area endow the scaffolds with enhanced cell viability to mesenchymal stem cells. The nanofibrous aerogels were further functionalized by SNF-mediated biomineralization, demonstrating their potential as a bone-mimicking scaffold. Our results show the potential of natural nanostructured silks in the field of biomaterials and provide a feasible strategy to construct protein nanofiber scaffolds.