Concerting magnesium implant degradation facilitates local chemotherapy in tumor-associated bone defect.

ABSTRACT

Effective management of malignant tumor-induced bone defects remains challenging due to severe systemic side effects, substantial tumor recurrence, and long-lasting bone reconstruction post tumor resection. Magnesium and its alloys have recently emerged in clinics as orthopedics implantable metals but mostly restricted to mechanical devices. Here, by deposition of calcium-based bilayer coating on the surface, a Mg-based composite implant platform is developed with tailored degradation characteristics, simultaneously integrated with chemotherapeutic (Taxol) loading capacity. The delicate modulation of Mg degradation occurring in aqueous environment is observed to play dual roles, not only in eliciting desirable osteoinductivity, but allows for modification of tumor microenvironment (TME) owing to the continuous release of degradation products. Specifically, the sustainable H2 evolution and Ca2+ from the implant is distinguished to cooperate with local Taxol delivery to achieve superior antineoplastic activity through activating Cyt-c pathway to induce mitochondrial dysfunction, which in turn leads to significant tumor-growth inhibition in vivo. In addition, the local chemotherapeutic delivery of the implant minimizes toxicity and side effects, but markedly fosters osteogenesis and bone repair with appropriate structure degradation in rat femoral defect model. Taken together, a promising intraosseous administration strategy with biodegradable Mg-based implants to facilitate tumor-associated bone defect is proposed.