Functional Nanoparticle‐Enhanced Silk Hydrogels for Tissue Engineering Biomaterials

Hydrogels prepared from natural polymers, such as silk fibroin, are useful in the field of tissue engineering due to their biocompatibility, biodegradability, and biological performance. However, poor mechanical properties can limit their broader utility. This study investigated reinforcing enzymatically crosslinked silk hydrogels with 130 nm silk nanoparticles (SNPs) to generate silk-silk composite materials with tunable strength and stiffness. The strength of the materials was dependent on SNP concentration, and hydrogels with Young's moduli of 14, 34, and 67 kPa were fabricated by adding no SNPs, 2 mg/mL SNPs, and 4 mg/mL SNPs, respectively. These methods were applied to silk bioinks using Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D printing to fabricate complex 3D structures with control of elasticity and modulus. Cylinders with Young's moduli of 17, 35, and 58 kPa were obtained with no SNPs, 2 mg/mL SNPs, and 4 mg/mL SNPs, respectively. SNPs were also preloaded with epidermal growth factor (EGF), relevant for tissue development and wound healing, and sustained release was achieved for over 15 days when embedded in hydrogels. Pilot studies of dermal fibroblast encapsulation in SNP-reinforced silk hydrogels demonstrated cytocompatibility. Tunable silk hydrogels reinforced with SNPs provide application-specific scaffolding for a variety of biomaterial and tissue engineering applications.