Engineering of micro- to nanostructured 3D-printed drug-releasing titanium implants for enhanced osseointegration and localized delivery of anticancer drugs

Abstract

Primary and secondary bone cancers are major causes of pathological bone fractures which are usually treated through implant fixation and chemotherapy. However, both approaches face many limitations. On one hand, implants may suffer from poor osseointegration, and their rejection results in repeated surgery, patient's suffering, and extensive expenses. On the other hand, there are severe systemic adverse effects of toxic chemotherapeutics which are administrated systemically. In this paper, in order to address these two problems, we present a new type of localized drug-releasing titanium implants with enhanced implants' biointegration and drug release capabilities that could provide a high concentration of anticancer drugs locally to treat bone cancers. The implants are fabricated by 3D printing of Ti alloy followed by an anodization process featuring unique micro- (particles) and nanosurface (tubular arrays) topography. We successfully demonstrate their enhanced bone osseointegration and drug loading capabilities using two types of anticancer drugs, doxorubicin (DOX) and apoptosis-inducing ligand (Apo2L/TRAIL). In vitro study showed strong anticancer efficacy against cancer cells (MDA-MB-231-TXSA), confirming that these drug-releasing implants can be used for localized chemotherapy for treatment of primary and secondary bone cancers together with fracture support.