A stalactite-inspired NIR/pH-responsive visualizable nano-platform for microenvironment-activated therapy of peri-implantitis-induced bone defects.

Abstract

Peri-implantitis is an inflammatory disease characterized by progressive peri-implant bone resorption. It poses a substantial challenge to the long-term survival of dental implants and imposes a considerable therapeutic burden. As the early stage of peri-implantitis is typically asymptomatic and difficult to detect, the optimal intervention window is often missed. Current reconstructive approaches primarily rely on invasive debridement or bone grafting, underscoring the need for a multifunctional therapeutic strategy that combines diagnostic capabilities, anti-inflammatory, and osteogenic properties. Inspired by the biomineralization process of stalactites, we developed a biomimetic composite CIMA (ACC@ICG/AZM@ALD) by encapsulating indocyanine green (ICG) and azithromycin (AZM) into amorphous calcium carbonate (ACC) and coating its surface with the bone-targeting ligand alendronate (ALD), thereby imparting the nanoplatform with antibacterial, anti-inflammatory, and osteoinductive properties. The introduction of AZM reshaped the peri-implant immune microenvironment and synergized with ICG, an FDA-approved NIR dye, to enhance antibacterial efficacy. <i>In vitro</i> assays demonstrated that CIMA could responsively trigger near-infrared (NIR) fluorescence upon exposure to the bone defect microenvironment, providing real-time visual warning. Furthermore, CIMA effectively scavenged reactive oxygen species (ROS), alleviated oxidative stress, and exerted potent anti-inflammatory and antibacterial effects against <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Streptococcus mutans</i> (<i>S. mutans</i>). Concurrently, it promoted the osteogenic differentiation of bone marrow-derived cells while suppressing osteoclastogenesis. <i>In vivo</i>, using a rat peri-implantitis model, CIMA facilitated bone regeneration within the inflamed peri-implant region. Collectively, this artificially engineered, stalactite-inspired CIMA system promoted bone regeneration and provided combined anti-inflammatory and antibacterial functions, offering a promising strategy for treating peri-implantitis.