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

作　　者：He Wang Xiaowei Chang Qian Ma Boyang Sun Han Li Jinmin Zhou Yiyao Hu Xiaoyu Yang Jie Li Xin Chen Jinlin Song 

机构地区：[1]Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences,Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education,College of Stomatology of Chongqing Medical University,Chongqing,401147,China [2]Department of Chemical Engineering,Shaanxi Key Laboratory of Energy Chemical Process Intensification,Institute of Polymer Science in Chemical Engineering,School of Chemical Engineering and Technology,Xi′an Jiaotong University,Xi′an,710049,China

出　　处：《Bioactive Materials》2023年第3期324-339,共16页生物活性材料（英文）

基　　金：National Natural Science Foundation of China(Grant No.31971282 and 82071072);Chongqing Graduate Tutor Team 2019(dstd201903).

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/β-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.

关 键 词：Periodontal bone regeneration Diabetes mellitus BIOINSPIRED HYDROGEL Drug delivery 

分 类 号：R587.1[医药卫生—内分泌]