Injectable Tumor Microenvironment-Modulated Hydrogels with Enhanced Chemosensitivity and Osteogenesis for Tumor-Associated Bone Defects Closed-Loop Management

Tumor microenvironment (TME)-modulated hydrogels were developed for closed-loop management postoperative tumor-associated bone effects responding to the shifted disease states. In early state, can modulate TME of residual tumors by depleting protons and glutathione, release chemotherapeutic agents enhance chemotherapy sensitivity, resulting in reduced metastasis attenuated side effects. late into regenerative scaffolds orchestrate long-lasting regeneration. • MTX-ss-MBGN showed drug loading capability osteoconductivity. TME-modulated enhanced chemosensitivity protons/GSH. ROS stress mitochondria-related damage tumor cells observed vitro. Hydrogels inhibited growth, lung promoted repair. Patients with defects need both repair states, but resistance, severe side-effects, poor regeneration result recurrence therapy failure. Herein, we develop an injectable hydrogel composed bio-responsive drug-loaded mesoporous bioactive glass nanoparticles (MBGN), gelatin (Gel), oxidized chondroitin sulfate (OCS) management. The deplete glutathione (GSH) within tissues sustained responsive-release capability, therefore interfering overcoming cancer also reducing off-target Mechanistically, state treatment, acidic environment will break Schiff’s base bond network hydrogels, thus deliver cells. Subsequently, pH-responsive amide bonds, GSH-responsive disulfide bonds acidity-degradable nanocarriers induce mitochondrial-related damage, activating p16-CYLD suppressor pathway apoptosis inhibit metastasis. exert osteogenesis Overall, steady avoid recurrence, achieving defects.