Abstract
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.
Highlights
Bone tumors represent one of the few fatal pathologies in orthopedics [1,2]
We introduced porosity within PMMA by adding up to 4% of carboxy methylcellulose (CMC) to improve control over both loading and de livery kinetics of cisplatin
We show that PMMA-based cements containing 3% of CMC i) release substantial amounts of cisplatin, ii) effectively kill osteosarcoma cells in vitro, and iii) exhibit compressive strengths similar to intact tibias ex vivo
Summary
Primary bone tumors are less prevalent than more common cancer types such as lung, prostate, and breast cancer. These primary malignant bone tumors are quite lethal with low overall 5-year survival rates of less than 20% without adjuvant chemotherapy [3], and occur mainly in young people [4]. Owing to the emergence of chemotherapy and advanced surgical techniques for tumor resection, the overall 5-year survival rate of primary bone malignancies has increased to 53–65% [5,6]. Novel and effective treatments preventing recurrence of primary malignant bone tumors after surgical resection are urgently needed
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