pH/ROS-responsive magnesium scaffold functionalized via hydrazone bonds for localized postoperative bone tumor therapy

Surgery remains the primary treatment strategy for bone tumors such as osteosarcoma; however, patients typically require postoperative radiotherapy and/or chemotherapy to prevent recurrence and metastasis. The implantation of scaffolds to restore bone mechanics is a routine surgical measure. Scaffold systems capable of localized drug release hold great clinical potential, as they can minimize systemic side effects associated with chemotherapy. In this work, we designed a pH/ROS-responsive magnesium scaffold functionalized via hydrazone bonds using micro-arc oxidation technology for controlled release of doxorubicin. Compared with simple physical adsorption, this chemical adsorption strategy markedly enhanced drug loading efficiency (508.4 ng vs. 793.5 ng). Under physiological conditions (pH 7.4), the scaffold released only 2.43 % of doxorubicin over 12 days, whereas in the tumor-mimicking acidic environment (pH 6.2), release reached 84.82 %. In contrast, scaffolds with simple adsorption released 27.68 % and 83 % under the same respective conditions. In vivo studies demonstrated that the intelligent scaffold did not impair wound healing but significantly inhibited osteosarcoma growth (87.67 %). These findings indicate that this responsive scaffold system provides a promising approach for localized postoperative bone tumor therapy with reduced systemic toxicity.