Photodynamic-Selenoprotein-Mobilizing System With Biofilm-Scavenging and Bone-Reconstruction Function in Diabetic Periodontitis

Objectives: The metabolic disorders in diabetic hyperglycemic pathological microenvironment could accelerate the progress of periodontitis, which remains a clinical challenge. Reactive oxygen species (ROS) accumulation and plaque biofilm residual in irregular deep periodontal pockets contribute to chronic inflammatory infiltration and over-activation of inflammatory responses, thus leading to refractory tissue damage and impaired bone regeneration. Therefore, we proposed a new strategy that can efficiently and minimal-invasively scavenge plaque biofilms, while also regulating over-activated chronic inflammation, as well as restoring the homeostasis of the endogenous tissue regeneration.
Methods: We synthesized aggregation-induced emission (AIE) frameworks， upon NIR activation this photodynamic therapy (PDT) could scavenge biofilm by releasing ROS. To eliminate the ROS-induced tissue damage, the selenocystine (Sec), an important ingredient for the selenium metabolism, was further bridged to the AIE system by the amide bond, which could mobilize the synthesis of selenoproteins and further alleviate the accumulated ROS and chronic inflammation infiltration. The biofilm scavenges and tissue regenerative function of this ROS balancing photodynamic-selenoproteins mobilizing system， and the potential intrinsic mechanisms were verified in vitro and diabetic periodontitis model in vivo.
Results: The photothermal effect and the released ROS-induced efficient bactericidal effect contribute to biofilm scavenging outcomes in vitro and in vivo. After the NIR activating stage and biofilm scavenge are completed, to neutralize the accumulated ROS, the synthesis of selenoproteins will be awakened and mobilized by the loaded Sec. The selenoproteins with antioxidation characteristics could interfere with ferroptosis in the diabetic microenvironment, restore endogenous homeostasis, and promote impaired bone regeneration in vitro and in vivo.
Conclusions: This study innovatively proposed a ROS balancing system combining photodynamic therapy with selenoproteins awakening properties, which shed light on refractory biofilm-related infectious bone regeneration in diabetes, such as periodontitis.