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Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets
Mei Li1, Mengyu Yao2, Weidan Wang3
1Department of Orthopedics, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Abstract:
Osteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy.
Insights
A novel bisphosphonate-loaded magnesium alloy pellet effectively inhibits osteosarcoma (OS) by inducing cell death and preventing recurrence. This innovative approach targets the mevalonate pathway for enhanced tumor eradication.
Area of Science:
- Biomaterials Science
- Oncology
- Orthopedic Surgery
Background:
- Osteosarcoma (OS) is a primary bone cancer with limited therapeutic advancements over the last 40 years.
- There is a critical need for novel strategies to prevent OS recurrence and improve treatment outcomes.
- Existing treatments often fall short in achieving complete tumor eradication and preventing metastasis.
Purpose of the Study:
- To develop and evaluate a novel bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet for osteosarcoma therapy.
- To elucidate the cellular and molecular mechanisms underlying the anti-OS effects of the developed biomaterial.
- To assess the potential of this innovative implant in preventing tumor recurrence and repairing defects post-resection.
Main Methods:
- Fabrication of hollow Mg-Sr alloy pellets with a MAO coating chemically conjugated with nitrogen-containing bisphosphonate.
- In vitro evaluation of the pellet's effects on OS cells in 2D and 3D culture environments, assessing apoptosis, necrosis, and invasion.
- In vivo studies to determine the therapeutic efficacy in destroying tumors and preventing recurrence, analyzing synergistic effects of Mg degradation and drug release.
Main Results:
- The BP-coated Mg pellets demonstrated significant inhibition of OS cells in vitro, inducing apoptosis, necrosis, and impairing tumor spheroid formation.
- In vivo, the pellets effectively destroyed tumors and prevented recurrence through combined magnesium degradation and bisphosphonate release.
- The anti-OS mechanism was identified as the inhibition of the mevalonate pathway at the molecular level.
Conclusions:
- The developed bisphosphonate-loaded MAO-coated Mg-Sr alloy pellet is a promising therapeutic agent for osteosarcoma.
- This novel biomaterial exhibits potent anti-tumor activity, eradicates existing tumors, and prevents recurrence.
- The findings suggest potential applications in post-surgical defect repair following osteosarcoma removal.
