Injectable Silk/Hydroxyapatite Nanocomposite Hydrogels with Vascularization Capacity for Bone Regeneration

Abstract Localized and sustained osteogenic-angiogenic stimulation to bone defects is critical for effective bone repair. Here, desferrioxamine (DFO) was loaded on silk fibroin nanofibers and blended with hydroxyapatite nanorods (HA), forming injectable DFO-loaded silk fibroin-HA nanocomposite hydrogels. The composite hydrogels remained homogeneous distribution of HA with high ratio (60%) and also higher stiffness than that of pure silk fibroin nanofiber hydrogels, which provided stable osteogenic stimulation niches for tissue regeneration. Without the scarify of injectability, the hydrogels achieved slow delivery of DFO for above 60 days, resulting in suitable angiogenesis in vitro and in vivo and better osteogenesis than DFO-free systems. Compared to previous injectable silk fibroin-HA hydrogels, the introduction of vascularization capacity further stimulated the osteogenic differentiation of stem cells and accelerated new bone formation. Quicker and better bone healing were detected at defect sites after the injection of DFO-loaded nanocomposite hydrogels, indicating the effective synergistic effect of osteogenic and angiogenic cues. This work provides a simple and effective strategy of introducing angiogenic cues to bone matrices. We believe that the injectable nanocomposite hydrogels are suitable for the regeneration of bone tissues.