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

• Published in: Bioactive materials Vol. 15; pp. 120 - 130
• Main Authors: Wang, Zhule, Nogueira, Liebert Parreiras, Haugen, Håvard Jostein, Van Der Geest, Ingrid CM, de Almeida Rodrigues, Patricia Caetano, Janssen, Dennis, Bitter, Thom, van den Beucken, Jeroen J.J.P., Leeuwenburgh, Sander CG
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.09.2022; KeAi Publishing; KeAi Communications Co., Ltd
• Subjects: Bone tumor treatment; Chemotherapeutic drug; Ex vivo biomechanical assessment; Local drug delivery; Porous polymethylmethacrylate cement; Ex vivo biomechanical assessment; Bone tumor treatment; Local drug delivery; Porous polymethylmethacrylate cement; Chemotherapeutic drug
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.12.023

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. [Display omitted] •Dual-functional porous PMMA cements are developed by introducing CMC as both pore generator and drug vehicle for cisplatin.•PMMA-based cements containing ≥3% CMC release sufficient amounts of chemotherapeutically active cisplatin.•PMMA-based cements containing ≤3% CMC retain sufficient mechanical properties for bone reconstruction at load-bearing sites.