A versatile nanoplatform with excellent biofilm permeability and spatiotemporal ROS regulation for peri-implantitis treatment

Rationale: Dental implant restoration is essential for rehabilitating dentition defects. However, peri-implantitis (PI) seriously threatens the long-term stability of implants. Treating PI requires the complete eradication of plaque biofilm and the meticulous modulation of inflammatory responses. Antibacterial photodynamic therapy (aPDT) presents a promising potential in the antibacterial realm. Nonetheless, traditional aPDT for PI faces challenges such as inadequate biofilm penetration and distribution of photosensitizers, as well as a lack of precise bacteria targeting. Moreover, the excessive ROS generated by aPDT will aggravate the oxidative stress of peri-implant tissues, and this issue cannot be neglected. Methods: The CuTA-Por@ε-PL nanoplatforms (CPP NPs) were synthesized and characterized using dynamic light scattering, transmission electron microscopy, and dye probes in detail. The antibacterial and anti-inflammatory activities of CPP NPs were evaluated both in vitro and in vivo. Moreover, the in vivo therapeutic efficacy was successively analyzed through micro-CT, hematoxylin and eosin staining, Masson's staining, immunofluorescence staining, and colony formation units (CFU), among other techniques. Results: Porphyrin (Por), CuTA nanozyme with SOD/CAT activities, and ε-Polylysine (ε-PL) were combined to fabricate CPP NPs via a straightforward approach. The notable positive charge of CPP NPs facilitated biofilm penetration, distribution and precise bacteria targeting. Then, irradiation with a 660 nm laser triggered a ROS burst for biofilm elimination. After aPDT, CPP NPs scavenged the residual ROS and modulated host immunity by regulating macrophage polarization. As a result, CPP-treated groups demonstrated the most outstanding antibacterial and anti-inflammatory performance in the rat PI model. Conclusions: Given the pathogenesis of PI, this strategy rationally designed a multifunctional NP with antibacterial and anti-inflammatory functions via spatiotemporal ROS regulation. It provides a potentially novel approach for PI treatment, which may have a profound impact on improving the prognosis of patients with PI and advancing the field of implant dentistry.