ZIF-8-Modified Multifunctional Hydrogel Loading siRNA and DOX for Postoperative Therapy of Maxillofacial Osteosarcoma and Bone Repair

The primary clinical challenges associated with postoperative maxillofacial osteosarcoma include high mortality rates and significant local recurrence. Additionally, patients often exhibit substantial bone defects that are incapable of self-healing, necessitating the implantation of scaffolds. Multifunctional hydrogels, which enable sustained local release of therapeutic agents and enhance scaffold surface properties, demonstrate significant potential for the postoperative management of maxillofacial osteosarcoma. In this study, doxorubicin (DOX) and PD-L1 siRNA were initially loaded into ZIF-8 to synthesize highly stable nanocomplex RNA-DOX@ZIF-8 (RDZ). Subsequently, a multifunctional hydrogel (Gel@RDZ) was fabricated by uniformly mixing RDZ with catechol-modified chitosan. Gel@RDZ exhibits a high drug-loading capacity, excellent viscoelasticity, and strong scaffold adhesion. In a rat femoral defect model, the Gel@RDZ-coated scaffold group demonstrated superior bone regeneration capabilities. Furthermore, in a murine osteosarcoma recurrence model, Gel@RDZ exhibited optimal immune cell infiltration, substantially reduced tumor recurrence, and markedly enhanced the tumor-killing efficacy of CD8⁺ T cells. Therefore, the development of a multifunctional hydrogel system (Gel@RDZ) provides a comprehensive treatment for postoperative maxillofacial osteosarcoma.