The clinical management of osteosarcoma remains a major therapeutic challenge, mainly owing to the high risk of tumor recurrence driven by residual cancer cells after surgical resection and the persistent difficulty in reconstructing irregular bone defects. To address these challenges, we engineered a Schiff base crosslinked, injectable, and dynamically responsive hydrogel platform composed of polyethyleneimine (PEI) and oxidized hyaluronic acid (OHA), with OHA serving as a structural backbone. We functionalized with osteogenic growth peptide (OGP) and small noncoding RNA (miR-143). Upon injection, the platform undergoes rapid in situ gelation, enabling precise localization at the tumor resection site and pH-responsive degradation-mediated sequential release of therapeutic agents. In vivo studies confirmed that the OHA-PEI-OGP/miR-143 hydrogel significantly inhibits osteosarcoma recurrence through sustained and localized delivery of miR-143 and OGP, thereby enhancing treatment efficacy while minimizing off-target effects. This localized delivery platform could possibly lessen the needed therapeutic dose and dosing frequency compared to regular systemic administration, reducing the danger of widespread off-target toxicity. Extensive in vitro and in vivo evaluations have illustrated that it not only significantly enhances bone regeneration but also effectively shifts the postoperative inflammatory environment towards an anti-inflammatory and regenerative condition. Together, these observations underscore its dual-function ability, particularly OHA-PEI-OGP/miR-143, in both preventing tumor return and aiding in bone repair, thereby presenting itself as an up-and-coming option for clinical use in intricate postoperative treatment of osteosarcoma. • A dynamically crosslinked hydrogel capable of in-situ injection and delivery of biological factors was prepared. • The miR-143 and osteogenic growth peptide were used to achieve antitumor and osteogenic dual-functional strategy. • The dynamic hydrogel responds to the tumor microenvironment, enhancing biological activity and therapeutic efficacy. • The antitumor and osteogenic activities of this hydrogel offer the possibility for osteosarcoma treatment.
Cang et al. (Sun,) studied this question.