A sono-responsive antibacterial nanosystem co-loaded with metformin and bone morphogenetic protein-2 for mitigation of inflammation and bone loss in experimental peri-implantitis
作者全名：Hu, Bo; Qiao, Wang; Cao, Yang; Fu, Xiaoming; Song, Jinlin
作者地址：[Hu, Bo; Fu, Xiaoming; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Hu, Bo; Fu, Xiaoming; Song, Jinlin] Chongqing Key Lab Oral Dis, Chongqing, Peoples R China; [Hu, Bo; Fu, Xiaoming; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Qiao, Wang] Chongqing Univ, Shapingba Hosp, Dept Stomatol, Chongqing, Peoples R China; [Cao, Yang] Chongqing Med Univ, Affiliated Hosp 2, Inst Ultrasound Imaging, Chongqing Key Lab Ultrasound Mol Imaging, Chongqing, Peoples R China
通信作者：Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Song, JL (通讯作者)，Chongqing Key Lab Oral Dis, Chongqing, Peoples R China.; Song, JL (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China.
来源：FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
ESI学科分类：Multidisciplinary
WOS号：WOS:001241802600001
JCR分区：Q1
影响因子：4.3
年份：2024
卷号：12
期号：
开始页：
结束页：
文献类型：Article
关键词：sono-responsive nanosystems; ultrasound stimulation; antibacterial; peri-implantitis; anti-inflammatory; bone repair
摘要：Background Dental implants have become an increasingly popular option for replacing missing teeth, and the prevalence of peri-implantitis has also increased, which is expected to become a public health problem worldwide and cause high economic and health burdens. This scenario highlights the need for new therapeutic options to treat peri-implantitis.Methods In this study, we proposed a novel sono-responsive antibacterial nanosystem co-loaded with metformin (Met) and bone morphogenetic protein-2 (BMP-2) to promote efficacy in treating peri-implantitis. We introduced the zeolitic imidazolate framework-8 (ZIF-8) as a carrier for hematoporphyrin monomethyl ether (HMME) to enhance the antibacterial effect of sonodynamic antibacterial therapy and tested its reactive oxygen species (ROS) production efficiency and bactericidal effect in vitro. Afterward, HMME-loaded ZIF-8, BMP-2-loaded polylactic acid-glycolic acid (PLGA), and Met were incorporated into gelatin methacryloyl (GelMA) hydrogels to form HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels, and the biocompatibility of which was determined in vitro and in vivo. A bacterial-induced peri-implantitis model in the maxilla of rats was established to detect the effects of the composite hydrogels with adjunctive use of ultrasound on regulating inflammation and promoting bone tissue repair in vivo.Results The results indicated that HMME@ZIF-8 with ultrasound stimulation demonstrated more better ROS production efficiency and antimicrobial efficacy. The composite hydrogels had good biocompatibility. Ultrasound-assisted application of the composite hydrogels reduced the release of the inflammatory factors IL-6 and TNF-alpha and reduced bone loss around the implant in rats with bacterial-induced peri-implantitis.Conclusion Our observations suggest that HMME@ZIF-8 may be a new good sonosensitizer material for sonodynamic antibacterial therapy. The use of HMME@ZIF-8/Met/BMP-2@PLGA/GelMA composite hydrogels in combination with ultrasound can provide a novel option for treating peri-implantitis in the future.
基金机构：National Natural Science Foundation of China10.13039/501100001809
基金资助正文：We kindly thank the National Engineering Research Center of Ultrasound Medicine for providing the ultrasonic therapeutic device.
