Silk fibroin-enhanced peptide self-assembled biomimetic hydrogel for 3D cell proliferation

Cell therapy has emerged as an innovative approach with great potential for treating various diseases. However, challenges such as insufficient quantities of transplanted cells hinder its effectiveness. In comparison to traditional two-dimensional expansion, three-dimensional (3D) cell culture can support higher cell proliferation rates and better preserve the normal functions and specific phenotypes of cells. Despite these advantages, creating a biomimetic 3D cell proliferation scaffold through mild, biocompatible methods remains a significant bottleneck in cell therapy. Peptide self-assembled hydrogels, with their biomimetic nanofiber network structure, provide an ideal environment for 3D cell expansion. However, their weak mechanical properties limit their use in long-term cell cultures. To address this, we introduce silk fibroin into the peptide self-assembled hydrogel. The macro-molecular silk fibroin template regulates the organization of short peptide molecules, enhancing their interactions and significantly improving the mechanical strength of the hydrogel. Experimental results show that the combination of silk fibroin and peptide solution creates a biomimetic hydrogel with enhanced mechanical properties under mild, physiological conditions. This hydrogel retains its nanofiber microstructure, exhibits low cytotoxicity, excellent biocompatibility, and good recoverability and injectability. Moreover, it supports rapid 3D cell proliferation, providing a sufficient number of cells for cell therapy. This work is a significant step toward advancing the clinical application of cell therapy.