Turning tumour migration into a therapeutic advantage: Local delivery of chemoattractants for glioblastoma control

Glioblastoma remains one of the most lethal solid tumours, with recurrence driven by highly migratory residual cells that escape resection and resist adjuvant radiochemotherapy and arise from underlying genetic heterogeneity that promotes both a migratory phenotype and therapy resistance. These invasive populations exploit endogenous chemotactic cues, including hypoxia induced signalling, postoperative wound-healing cytokines, perivascular niche factors, and interstitial or cerebrospinal-fluid-driven transport, to disperse through the brain and re-establish tumour mass. While efforts to therapeutically inhibit chemokine pathways have been extensive, clinical trials targeting CXCR4, CCR2, CCR5, and CXCR1/2 have demonstrated limited survival benefit, in part due to ligand-receptor redundancy, network compensation, and the inherently spatial nature of chemotactic signalling. Emerging strategies instead seek to exploit chemotaxis by engineering chemoattractant gradients capable of directing glioblastoma cells toward a defined location, such as an implantable scaffold or hydrogel placed in the resection cavity. This review synthesises the biological principles underlying chemokine- driven migration, the spatial organisation of tumour- associated gradients, and the engineering considerations required to generate stable, localised chemotactic fields. We give an overview of biomaterial platforms designed for chemokine delivery and summarise the preclinical evidence supporting tumour cell trapping or redirection in vivo. Finally, we outline the major biological, engineering, and regulatory barriers to translation, including gradient stability, unintended immune recruitment, fluid-flow-driven distortion, chemokine instability, and sterilisation challenges. Together, these insights establish a conceptual and practical framework for using engineered chemotactic guidance as a therapeutic strategy and highlight opportunities for next-generation "migration-sink" devices to improve local control of glioblastoma.