Functional-responsive hydrogel microspheres based on microenvironment sensing promote the sequential repair of infected bone defects by regulating ROS balance

The key to treating infectious bone defects (IBD) is regulating reactive oxygen species (ROS) balance to achieve “anti-infective first, then osteogenesis” temporal sequential repair. However, sensing microenvironmental changes to regulate ROS remains challenging. This study prepared a nanoparticle (PBD-ICG nanoparticlces) capable of sensing pH changes to enable protonation and deprotonation with “triple-element synergy” acid-base-driven assembly method, and loaded onto GelMA/HAMA hydrogel microsphere established a functional-responsiveness hydrogel microsphere (PGI) based on microenvironment sensing. With ultrasonic cavitation, indocyanine green transition to excited state, enabling electron transfer or energy transfer with H 2 O or 3 O₂ in microenvironment to generate ROS. Under 1 W ultrasound, ROS release 74% to anti-bacteria and restores acidic infected microenvironment to normal weakly alkaline state. Simultaneously, nanoparticles sense pH changes, triggering internal polyaniline transform to emeraldine base and bovine serum albumin conformational changes. This process releases deferoxamine to inhibit excess ROS with 72% efficiency, regulating ROS balance and promoting vascularized osteogenesis. In vitro experiments confirmed a 9.19-fold increase in angiogenesis. In vivo studies revealed 82.6% antibacterial efficacy, followed by 46.5% improvement in osteogenesis efficacy, achieving temporal sequential treatment. Summarizing, this system regulates ROS balance through sensing of microenvironment to achieve functional-responsive temporal sequential repair, providing novel strategies for IBD synergistic repair.