ROS-Scavenging Electroactive Polyphosphazene-Based Core–Shell Nanofibers for Bone Regeneration

Bone defects are always accompanied by inflammation due to excessive reactive oxygen species (ROS) in injured regions, which greatly impedes the regeneration of bone tissues. Although many conductive polymers have been developed to scavenge ROS, they are typically non-degradable under physiological conditions, making them unsuitable for in vivo applications. Biodegradable polyorganophosphazenes (POPPs) may serve as potent ROS-scavenging biomaterials owing to their versatile chemical structures and ease of functionalization. Herein, a PATGP-type electroactive polyphosphazene with side groups of aniline tetramer and glycine ethyl ester was compared to conventional poly(lactic-co-glycolic acid) (PLGA) in regenerating bone tissues. To conduct in vitro and in vivo evaluations, three kinds of electrospun nanofibrous meshes were prepared: PLGA, PLGA/PATGP blend, and PLGA/PATGP core–shell nanofibers. Among them, PLGA/PATGP core–shell nanofibers outperform the blend and PLGA nanofibers in terms of scavenging ROS, promoting osteogenic differentiation, and accelerating neo-bone formation. The continuous PATGP shell on the PLGA/PATGP core–shell nanofiber surface could apparently provide more significant modulation effects on cellular behaviors than the PLGA/PATGP blend nanofibers with PATGP dispersed in the PLGA matrix. Therefore, the core–shell structured PLGA/PATGP nanofibers were envisioned as a promising candidate scaffold for bone tissue engineering. Additionally, the core–shell design paved the way for biomedical applications of functional POPPs in combination with other polymeric biomaterials, without phase separation or difficulty of increasing the molecular weights of POPPs. Graphical abstract