Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration

作者全名："Wang, He; Chang, Xiaowei; Ma, Qian; Sun, Boyang; Li, Han; Zhou, Jinmin; Hu, Yiyao; Yang, Xiaoyu; Li, Jie; Chen, Xin; Song, Jinlin"

作者地址："[Wang, He; Ma, Qian; Sun, Boyang; Li, Han; Zhou, Jinmin; Hu, Yiyao; Yang, Xiaoyu; Li, Jie; Song, Jinlin] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Coll Stomatol, Chongqing 401147, Peoples R China; [Chang, Xiaowei; Chen, Xin] Xi An Jiao Tong Univ, Inst Polymer Sci Chem Engn, Sch Chem Engn & Technol, Dept Chem Engn, Xian 710049, Peoples R China"

通信作者："Li, J; Song, JL (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Coll Stomatol, Chongqing 401147, Peoples R China.; Chen, X (通讯作者)，Xi An Jiao Tong Univ, Inst Polymer Sci Chem Engn, Sch Chem Engn & Technol, Dept Chem Engn, Xian 710049, Peoples R China."

来源：BIOACTIVE MATERIALS

ESI学科分类：　

WOS号：WOS:000862503400001

JCR分区：Q1

影响因子：14.593

年份：2023

卷号：21

期号：　

开始页：324

结束页：339

文献类型：Article

关键词：Periodontal bone regeneration; Diabetes mellitus; Bioinspired; Hydrogel; Drug delivery

摘要："Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(DL-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell ""recruitment-osteogenesis"" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simulta-neously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/beta-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration."

基金机构："National Natural Science Foundation of China [31971282, 82071072]; Chongqing Graduate Tutor Team 2019 [dstd201903]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (Grant No. 31971282 and 82071072) and Chongqing Graduate Tutor Team 2019 (dstd201903).