Dual-functional porous and cisplatin-loaded polymethylmethacrylate cement for reconstruction of load-bearing bone defect kills bone tumor cells  

作　　者：Zhule Wang Liebert Parreiras Nogueira Håvard Jostein Haugen Ingrid CM.Van Der Geest Patricia Caetano de Almeida Rodrigues Dennis Janssen Thom Bitter Jeroen J.J.P.van den Beucken Sander CG.Leeuwenburgh 

机构地区：[1]Radboud University Medical Center,Department of Dentistry-Regenerative Biomaterials,Radboud Institute for Molecular Life Sciences,Nijmegen,the Netherlands [2]University of Oslo,Department of Biomaterials,Institute of Clinical Dentistry,Faculty of Dentistry,Oslo,Norway [3]Radboud University Medical Center,Department of Orthopedics,Radboud Institute for Health Sciences,Nijmegen,the Netherlands

出　　处：《Bioactive Materials》2022年第9期120-130,共11页生物活性材料（英文）

摘　　要：Malignant bone tumors are usually treated by resection of tumor tissue followed by filling of the bone defect with bone graft substitutes.Polymethylmethacrylate(PMMA)cement is the most commonly used bone substitute in clinical orthopedics in view of its reliability.However,the dense nature of PMMA renders this biomaterial unsuitable for local delivery of chemotherapeutic drugs to limit the recurrence of bone tumors.Here,we introduce porosity into PMMA cement by adding carboxymethylcellulose(CMC)to facilitate such local delivery of chemotherapeutic drugs,while retaining sufficient mechanical properties for bone reconstruction in load-bearing sites.Our results show that the mechanical strength of PMMA-based cements gradually decreases with increasing CMC content.Upon incorporation of≥3%CMC,the PMMA-based cements released up to 18%of the loaded cisplatin,in contrast to cements containing lower amounts of CMC which only released less than 2%of the cisplatin over 28 days.This release of cisplatin efficiently killed osteosarcoma cells in vitro and the fraction of dead cells increased to 91.3%at day 7,which confirms the retained chemotherapeutic activity of released cisplatin from these PMMA-based cements.Additionally,tibias filled with PMMA-based cements containing up to 3%of CMC exhibit comparable compressive strengths as compared to intact tibias.In conclusion,we demonstrate that PMMA cements can be rendered therapeutically active by introducing porosity using CMC to allow for release of cisplatin without compromising mechanical properties beyond critical levels.As such,these data suggest that our dual-functional PMMA-based cements represent a viable treatment option for filling bone defects after bone tumor resection in load-bearing sites.

关 键 词：Porous polymethylmethacrylate cement Bone tumor treatment Local drug delivery Chemotherapeutic drug Ex vivo biomechanical assessment 

分 类 号：R738.1[医药卫生—肿瘤] R318.08[医药卫生—临床医学]