Bone-Adhesive Peptide Hydrogel Loaded with Cisplatin for Postoperative Treatment of Osteosarcoma.

The inhibition of residual tumor recurrence while repairing bone defects poses a challenging issue for postoperative osteosarcoma treatment. Here, we develop a self-assembling peptide hydrogel (GelA) for the targeted delivery of cisplatin (CDDP), aiming to integrate postoperative tumor inhibition with bone defect repair. GelA exhibits exceptional biocompatibility, high loading capacity for CDDP, and superior bone adhesion. After in situ injection to bone defects, CDDP-loaded hydrogel GelA-CDDP demonstrates a strong affinity for hydroxyapatite, thereby facilitating optimal bone adhesion and prolonging the retention time of CDDP in a postoperative wound. Furthermore, GelA-CDDP can regulate the distribution and release behavior of CDDP, minimizing off-target effects and optimizing the therapeutic outcomes of chemotherapy and osteogenesis. Finally, in the orthotopic osteosarcoma transplantation model in mice, postoperative treatment with GelA-CDDP significantly inhibits residual osteosarcoma recurrence as well as repair of bone defects through synergistic osteogenesis promotion and osteoclastic inhibition. We believe that this hydrogel-based therapy strategy holds great promise in achieving simultaneous tumor inhibition and bone defect repair for postoperative osteosarcoma treatment.