Thermosensitive injectable in situ forming hydrogel incorporating anti-oxidative stress and anti-inflammatory nanoparticles for vital pulp therapy of pulpitis

含有抗氧化应激和抗炎纳米粒子的热敏可注射原位成型水凝胶用于牙髓炎的活髓治疗

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作者:Lixin Zhang, Xianling Ning, Jingyi Cui, Yanqiang Zhao, Fei Xie, Ningxin Zhu, Dan Wang, Man Qin, Zhiqiang Lin, Yuanyuan Wang

Abstract

Vital pulp therapy is critically important for the long-term preservation of teeth with pulpitis. However, the anti-inflammatory effects of pulp-capping materials used in clinics remain unsatisfactory. Pulpitis is tightly connected with oxidative stresses; therefore, scavenging excessive reactive oxygen species (ROS) is a prospective treatment. Here a thermosensitive and injectable hydrogel that forms in situ was developed. By using poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide)-based triblock copolymer (PPP) as a scaffold to carry Prussian blue nanoparticles (PBNPs), with effective ROS scavenging capability via multiple enzyme-like activities, such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD)activities. The developed PBNPs@PPP demonstrated anti-oxidative stress and anti-inflammation capabilities in vitro. As a direct pulp capping material, PBNPs@PPP suppressed inflammation progression in pulpitis in rats while also reducing cell necrosis and inflammatory cell infiltration in pulp tissue. RNA sequencing analyses showed that the functions of PBNPs@PPP were highly involved in anti-inflammatory pathways. Through experimental verification, it was found that PBNPs@PPP suppressed inflammation progression in pulpitis by inhibiting the NF-κB/NLRP3 pathway, which reduced the transmission of downstream inflammation pathways. Overall, use of this PBNPs@PPP hydrogel has potential to be a new, safe and efficient strategy for vital pulp therapy to treat pulpitis.

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