Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect  

作　　者：Qingqing Guan Tu Hu Lei Zhang Mengjiao Yu Jialin Niu Zhiguang Ding Pei Yu Guangyin Yuan Zhiquan An Jia Pei 

机构地区：[1]National Engineering Research Center of Light Alloy Net Forming,Center of Hydrogen Science&State Key Laboratory of Metal Matrix Composite,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai,200240,China [2]Department of Orthopedics,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai Jiao Tong University,Shanghai,200233,China [3]Department of Orthopedics,Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Jiao Tong University,Shanghai,200025,China [4]Institute of Medical Robotics&National Engineering Research Center for Advanced Magnetic Resonance Technologies for Diagnosis and Therapy,Shanghai Jiao Tong University,Shanghai,200240,China

出　　处：《Bioactive Materials》2024年第10期445-459,共15页生物活性材料（英文）

基　　金：supported by the National Key Research&Development Program of China(2021YFE0204900);the National Natural Science Foundation of China(52222108);Science and Technology Commission of Shanghai Municipality(22ZR1432000,23JC1402400).

摘　　要：Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects,substantial tumor recurrence,and long-lasting bone reconstruction post tumor resection.Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices.Here,by deposition of calcium-based bilayer coating on the surface,a Mg-based composite implant platform is developed with tailored degradation characteristics,simultaneously integrated with chemotherapeutic(Taxol)loading capacity.The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles,not only in eliciting desirable osteoinductivity,but allows for modification of tumor microenvironment(TME)owing to the continuous release of degradation products.Specifically,the sustainable H_(2) evolution and Ca^(2+) from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction,which in turn leads to significant tumor-growth inhibition in vivo.In addition,the local chemotherapeutic delivery of the implant minimizes toxicity and side effects,but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model.Taken together,a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.

关 键 词：Tumor-associated bone defect Biodegradable magnesium-based implant Multifunctional composite coating Bone regeneration Local tumor therapy 

分 类 号：R318.08[医药卫生—生物医学工程] TG146.22[医药卫生—基础医学]