Engineering Osteoimmune Responses with Functionalized Orthopedic Implants for Post‐Operative Osteosarcoma Treatment

Surgery is a mainstream treatment of osteosarcoma in the clinic, which often causes critical-size bone defects due to its highly invasive nature. However, the post-operative osteosarcoma management still remains challenging, characterized by high risks of recurrence and insufficient defect recovery. Recent studies increasingly reveal that the osteoimmune system is a crucial mediator of bone homeostasis and immune protection functions, emerging as a crucial nexus linking the antitumor immunity and osteopromotion regimes. Consequently, there is significant interest to develop new strategies to modulate the immune responses in the post-operative defect site, aiming to sustainably inhibit residual tumor growth and recurrence while accelerating defect regeneration. Interestingly, orthopedic implants emerge as optimal platforms for the on-demand engineering of immune responses in the post-operative defects in a highly integrative approach. Herein, a comprehensive review is provided on the principles and designs of osteoimmunomodulatory orthopedic implants for evoking osteosarcoma-specific immunity while boosting osseointegration and bone defect recovery. Overall, osteoimmunomodulatory orthopedic implants offer immense potential for ameliorating the osteosarcoma treatment outcome by improving patient survival and quality of life.