Biomaterial-based strategies for postoperative residual tumors: From margin clearance to immune control and tissue repair

Postoperative and post-ablation residual tumors represent a major yet underrecognized source of cancer recurrence, metastasis, and therapeutic failure. Distinct from primary tumors, residual lesions are typically sparse, spatially dispersed, and embedded within dynamically evolving microenvironments shaped by wound healing, inflammation, hypoxia, and immune imbalance. These features create pronounced spatiotemporal blind spots that limit the effectiveness of conventional systemic therapies and necessitate treatment strategies capable of precise local intervention, coordinated multimodal action, and active microenvironmental reconstruction. This review examines recent advances in nanomaterial-based approaches for the management of postoperative residual tumors, encompassing intraoperative and early postoperative nanotechnologies for high-resolution margin visualization and immediate disease clearance, as well as localized and sustained delivery systems-including hydrogels, implantable scaffolds, and microenvironment-responsive nanoparticles-that overcome spatial inaccessibility and temporal mismatch through prolonged retention and controlled activation. Multifunctional nanoplatforms integrating physical ablation, chemical or metabolic intervention, immune modulation, and tissue-supportive architectures are further highlighted for their ability to induce immunogenic cell death, remodel immunosuppressive niches, and concurrently promote postoperative tissue repair and functional recovery. Key challenges limiting clinical translation, including long-term biosafety, residual tumor heterogeneity, incomplete mechanistic resolution of immune effects, and the lack of standardized evaluation frameworks, are also discussed. By framing residual tumors as a coupled problem of tumor eradication and postoperative microenvironmental reconstruction, this review provides a unified conceptual framework to guide the rational design of nanomaterials for durable control of residual disease.