Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel

查看全文 作　　者：Zehao [1,2,3]Jing;Renhua [1,2]Ni;Jiedong [1,2,3]Wang;Xinhong [1,2,3]Lin;Daoyang [1,2,3]Fan;Qingguang [1,2,3]Wei;Teng [1,2,3]Zhang;Yufeng [4]Zheng;Hong [1,2]Cai;Zhongjun [1,2,3]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]Department of Materials Science and Engineering,College of Engineering,Peking University,Beijing,100871,People’s Republic of China

出　　处：《Bioactive Materials》索引2021年第6卷第12期,共16页

基　　金：This work was supported by the Ministry of Science and Technology of the People’s Republic of China[grant number 2016YFB1101501];the National Natural Science Foundation of China[grant number 81772320]. 摘　　要：Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma;however,intraoperative bone defects,local tumour recurrence,and chemotherapy-induced adverse effects still affect the quality of life of patients.Emerging 3D-printed titanium alloy(Ti6Al4V)implants have advantages over traditional implants in bone repair,including lower elastic modulus,lower stiffness,better bone conduction,more bone in-growth,stronger mechanical interlocking,and lager drug-loading capacity by their inherent porous structure.Here,cisplatin,a clinical first-line anti-osteosarcoma drug,was loaded into Ti6Al4V implants,within a PLGA-PEG-PLGA thermo-sensitive hydrogel,to construct bone substitutes with both anti-osteosarcoma and bone-repair functions.The optimal concentrations of cisplatin(0.8 and 1.6 mg/mL)were first determined in vitro.Thereafter,the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants,as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse,and bone defect rabbit models,respectively.The loading of cisplatin reduced tumour volume by more than two-thirds(from 641.1 to 201.4 mm3)with negligible organ damage,achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery.Although bone repair was hindered by cisplatin loading at 4 weeks,no difference was observed at 8 weeks in the context of implants with versus without cisplatin,indicating acceptable long-term stability of all implants(with 8.48%-10.04%bone in-growth and 16.94%-20.53%osseointegration).Overall,cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects,and should be considered for clinical use. 关键词：3D-printed titanium alloy Orthopaedic implant OSTEOSARCOMA Hydrogel Local chemotherapy

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Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel

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