Bioactive silk hydrogels with tunable mechanical properties

Developing bioactive hydrogels with potential to guide the differentiation behavior of stem cells has become increasingly important in the biomaterials field. Here, silk hydrogels with tunable mechanical properties were developed by introducing inert silk fibroin nanofibers (SNF) within an enzyme crosslinked system of regenerated silk fibroin (RSF). After the crosslinking reaction of RSF, the inert SNF was embedded into the RSF hydrogel matrix, resulting in improved mechanical properties. Tunable stiffness in the range of 9-60 KPa was achieved by adjusting the amount of the added NSF, significantly higher than SNF-free hydrogels formed under same conditions (about 1 KPa). In addition, the proliferation of rat bone marrow derived mesenchymal stem cells cultured on the composite hydrogels and differentiated into endothelial cells, myoblast and osteoblast cells was improved, putatively due to the control of stiffness of the hydrogels. Bioactive and tunable silk-based hydrogels were prepared via a composite SNF and crosslinked RSF system, providing a new strategy to design silk biomaterials with tunable mechanical and biological performance.