Inflammation-regulated and nutrient-supplied scaffolds promote bone regeneration in diabetic microenvironment in vivo

The harsh microenvironment of persistent inflammation and insufficient nutrient supply in diabetic organism impedes severely the osteogenic differentiation. Current management on diabetic microenvironment regulation has been focused on glycemic control and eliminating reactive oxygen species (ROS), which is inefficient to modulate the harsh diabetic microenvironment to promote bone regeneration. Herein, a surface-functionalized black phosphorus nanosheets (BPNSs)-coated ROS-scavenging scaffold was designed for the bone healing in type-2 diabetic rats by contributing to nutrient provision, osteogenesis, and anti-inflammation. The BPNSs/tannic acid (TA) were surface coated with cyclodextrin loaded with simvastatin (SIM)/4-carboxy-2-fluorobenzeneboronic acid (FPBA)-grafted hyperbranched poly-l-lysine (HBPL), which were further modified onto the pore walls of poly(lactide-co-glycolide) (PLGA) scaffold. The BPNSs gradually degraded to release phosphate, which served as an important component of bone, and together with the released SIM, synergistically promoted osteogenesis differentiation of MC3T3-E1 cells in a β-glycerophosphate-free medium. The TA and FPBA on the scaffold alleviated the inflammatory environment by ROS depletion and downregulating inflammatory factors, resulting in better bone regeneration in skull defects of diabetic rats in vivo. The remarkable outcomes in vivo verify that the scaffold containing functionalized BPNSs provides an effective strategy for diabetic bone regeneration.