Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects  

作　　者：Zehao Jing Wanqiong Yuan Jiedong Wang Renhua Ni Yu Qin Zhinan Mao Feng Wei Chunli Song Yufeng Zheng Hong Cai Zhongjun Liu 

机构地区：[1]Department of Orthopedics,Peking University Third Hospital,Beijing,100191,People’s Republic of China [2]Engineering Research Center of Bone and Joint Precision Medicine,Ministry of Education,Beijing,100191,People’s Republic of China [3]Beijing Key Laboratory of Spinal Disease Research,Beijing,100191,People’s Republic of China [4]School of Materials Science and Engineering,Peking University,Beijing,100871,People’s Republic of China

出　　处：《Bioactive Materials》2024年第3期223-241,I0002-I0004,共19页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China(grant number 82272456 and 82202748);China Postdoctoral Science Foundation(grant number 2022M720297).

摘　　要：Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment.A three-dimensional(3D)-printed porous Ti6Al4V scaffold(3DTi)is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants,including a lower elasticity modulus,stronger bone-implant interlock,and larger drug-loading space.Simvastatin is a multitarget drug with anti-tumor and osteogenic potential;however,its efficiency is unsatisfactory when delivered systematically.Here,simvastatin was loaded into a 3DTi using a thermosensitive poly(lactic-co-gly-colic)acid(PLGA)-polyethylene glycol(PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and oste-ogenic effects.Newly constructed simvastatin/hydrogel-loaded 3DTi(Sim-3DTi)was comprehensively appraised,and its newfound anti-osteosarcoma mechanism was explained.Specifically,in a bone defect model of rabbit condyles,Sim-3DTi exhibited enhanced osteogenesis,bone in-growth,and osseointegration compared with 3DTi alone,with greater bone morphogenetic protein 2 expression.In our nude mice model,simvastatin loading reduced tumor volume by 59%-77%without organic damage,implying good anti-osteosarcoma activity and biosafety.Furthermore,Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro.Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects,with a ferroptosis-mediated anti-osteosarcoma effect.

关 键 词：3D-printed titanium alloy IMPLANT SIMVASTATIN OSTEOSARCOMA Ferroptosis 

分 类 号：TQ427.26[化学工程] R318[医药卫生—生物医学工程] R738.1[医药卫生—基础医学]