A photothermally catalytic nanocomposite dual-crosslinked hydrogel for all-in-one postoperative osteosarcoma bone repair

Osteosarcoma is among the most aggressive primary bone malignancies in adolescents. Postoperative reconstruction presents a “dual challenge”: complete eradication of residual tumor tissue is required to minimize recurrence, while maximal preservation of surrounding tissues and functional regeneration of bone defects must be achieved. In this study, biomimetic nano–bone minerals based on Zn 2+ /Ce 3+ -substituted whitlockite (Zn 2+ /Ce 3+ -WH) were integrated into a dual-crosslinked hydrogel scaffold constructed from GelMA and GelDA, yielding a GDWH nanocomposite scaffold for an “all-in-one” postoperative osteosarcoma therapy. Under near-infrared irradiation, GDWH exhibited excellent photothermal performance, enabling pronounced photothermally induced ablation of osteosarcoma cells. Meanwhile, the accelerated redox cycling within GDWH efficiently scavenged excessive reactive oxygen species (ROS), thereby suppressing inflammatory responses and protecting adjacent tissues. Furthermore, under an osteoimmune-regulated microenvironment, the GDWH scaffold markedly enhanced osteogenic differentiation and promoted angiogenesis, consequently accelerating bone regeneration within the defect region. Overall, by integrating the triad of “tumor ablation–tissue protection–regenerative repair” into a single platform, the GDWH dual-crosslinked nanocomposite hydrogel scaffold offers a translationally promising, comprehensive solution for the complex postoperative pathology of osteosarcoma and provides new insights into multimodal synergistic therapeutic strategies for osteosarcoma. • The NIR-triggered photothermal effect of the dual-crosslinked nanocomposite hydrogel (GDWH) enables efficient eradication of residual osteosarcoma cells. • The dual-ion release system of GDWH effectively scavenges excessive ROS and suppresses inflammatory responses. • The composite scaffold promotes angiogenesis and facilitates osteogenic differentiation within an immunomodulatory microenvironment.