P10.14.A Caught in a trap: Silk fibroin, hyaluronic acid, and heparin sponges to capture residual glioblastoma cells

Abstract Background Recurrent glioblastoma (GBM) is today inevitable, even using an aggressive treatment protocol (surgery, radiotherapy, and chemotherapy). It mostly occurs within 2 cm of the resection cavity due to invasion ability GBM cells. The aim this work test qualify a local integrative approach nano-based chemokine-cancer cell trap concept lure residual cells by releasing chemoattractive molecules and, ultimately, confine kill them in biomimetic nanostructured polymeric scaffold. Material Methods stromal cell-derived factor 1α (SDF-1α) was used here as chemoattractant its synergy with CXCR4 receptor, correlation axis migration infiltrating Freeze-dried sponges (20 140μm/pore size) composed silk fibroin (SF), hyaluronic acid (HA), heparin (hep) charged SDF-1α evaluated trap. First, cytocompatibility biodegradability were both vitro vivo. Secondly, molecular functional responses U87MG-CXCR4+ cells, that constitutively stably expressed receptor RFP, reporters. To assess response gradient vitro, transwell, under-agarose, agarose drop assays used. spheroids cultivated verify hosting capacity scaffolds. Finally, syngeneic xenogeneic models developed evaluate bioperformance Results SF-HA-hep presented low cytotoxicity complete biodegradation after 4 months implantation. Histological analysis revealed only reaction, immune short-term study, but no signs acute inflammation or fibrotic process found at cavity-brain margin long-term demonstrating fine tolerability Relevant involved chemotaxis (Akt, Erk, Paxillin) activated upon SDF-1α. directionally attracted SDF-1α-loaded sponges, also larger neurosphere infiltration area observed these compared controls. Preliminary observations have shown clusters detached from main tumor mass towards implanted sponge. This may be indicative chemoattraction, DAPI correlated Ki67 staining front. Further analyses including CXCR4, CD44, paxillin, galectin-1 immunolabeling will performed confirm hypothesis. Conclusion Overall, results showed are biocompatible suitable use for strategy can overcome resistance GB, potentially transferred clinic future.