3D-Printed Nanoporous Scaffolds Impregnated with Zoledronate for the Treatment of Spinal Bone Metastases
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MRS Advances © 2019 Materials Research Society DOI: 10.1557/adv.2019.156
3D-Printed Nanoporous Scaffolds Impregnated with Zoledronate for the Treatment of Spinal Bone Metastases Elie Akoury1, Michael H. Weber1*, Derek H. Rosenzweig1* 1
Department of Surgery, Division of Orthopaedics, McGill University and The Research Institute of the McGill University Health Centre, Injury Repair Recovery Program, Montreal, QC.
* To whom correspondence should be addressed.
ABSTRACT:
Zoledronate (Zol) is a bone-preserving/ anti-tumoral drug that is widely used for the treatment of many cancers including spinal bone metastases. High systemic Zol doses required to elicit an adequate effect in the spine often lead to significant side effects, limiting its prolonged use and effectiveness. Here, we aim to provide an alternative strategy to locally deliver Zol at the tumor site. We show that nanoporous 3D-printed scaffolds can be loaded with Zol and possess the ability to release Zol (10-28%) over a sustained period. Additionally, we demonstrate that Zol-impregnated scaffolds, mostly Gel Lay, impair the proliferation of the prostate cancer cell line LAPC4 and the prostate-induced bone metastasis cells in vitro. 3D-printed nanoporous polymers offer a novel and versatile opportunity for potential local delivery of drugs in future clinical settings. These polymers can decrease systemic exposure and related side effects of Zol while at the same time concentrating the drug effect at the tumor site thereby inhibiting tumor proliferation. Also, these scaffolds could be co-printed or coupled with other materials to produce custom implants that offer better structural support for bone growth at the tumor site following resection.
INTRODUCTION Primary breast, lung, and prostate cancers very often metastasize to bone, particularly to the spine. Bone metastasis compromises the structural integrity of the bone and significantly impacts patient quality of life by inducing pain or reducing functional independence [1]. Surgical excision is one treatment option and is often
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extensive to eliminate all malignant tissue and prevent new tumor formation [2]. The resulting large defects will not heal spontaneously requiring reconstruction with autologous bone grafting which is usually insufficient. Along with radiotherapy, current non-surgical therapies focus on chemotherapy and bone preservation, with doxorubicin (Dox) and zoledronate (Zol) being respectively some of the most common. These drugs are usually systemically delivered to patients, and they can cause multiple adverse effects. While high doses of Dox are associated with cardiac toxicity [3], high amounts of Zol often cause flu-like symptoms and, to a lesser extent, joint pain, osteonecrosis of jaw and renal toxicity [4]. To overcome these
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