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

Abstract 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.