Biodegradable microspheres made of conductive polyorganophosphazene showing antioxidant capacity for improved bone regeneration

Abstract Reactive oxygen species (ROS) are likely to accumulate around severe bone defects, which jeopardizes activities of surrounding cells and hampers new bone formation. An effective strategy to address this issue is to develop scaffolding biomaterials with both antioxidant and osteoinductive capacities. An aniline tetramer (AT) and glycine ethyl ester co-substituted polyorganophosphazene (PATGP) was synthesized, and expected to meet the demands, since the AT moieties were antioxidant and the phosphorus-rich phosphazene moieties were osteocompatible. Moreover, the AT endowed the PATGP with conductivity to match the electrophysiology of bone tissues. By applying in vitro cell culture and in vivo evaluations, microsphere-type scaffolds made of PATGP were systematically characterized on their capacities including ROS-scavenging effect, cytotoxicity and osteoinductivity, using non-conductive poly[(ethylalanato)(ethylglycinato)]phosphazene (PAGP) and poly(lactide-co-glycolide) (PLGA) microspheres as control groups. Among them, PATGP microspheres demonstrated the strongest promotion effects on up-regulating cellular activities and on speeding up neobone formation in rat calvarial defects. Compared to polyester-type biomaterials, in summary, polyorganophosphazenes demonstrated strong flexibility in functionalization by introducing supplementary features such as antioxidant activity and electroactivity, which made them to be quite efficient in enhancing osteogenesis.