4.7 Article

Development of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem-Like Cells with CXCL12-Mediated Chemotaxis

Journal

ADVANCED HEALTHCARE MATERIALS
Volume 12, Issue 14, Pages -

Publisher

WILEY
DOI: 10.1002/adhm.202300671

Keywords

cell migration; collagen-hyaluronic acid hydrogel; controlled delivery; CXCL12 chemotaxis; glioblastoma cells; glioblastoma stem-like cells; thiol-Michael addition hydrogel

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This study aims to further develop a thiol-Michael addition injectable hydrogel to capture and attract infiltrative glioblastoma cells and therapy-resistant glioblastoma stem-like cells (GSCs) through CXCL12-mediated chemotaxis. The results demonstrate that CXCL12 released from the synthetic hydrogel can induce the migration of GBM cells and GSCs from the extracellular matrix and promote invasion into the hydrogel through amoeboid migration. This synthetic hydrogel shows promise as a method to attract and capture migratory GBM cells and GSCs responsive to CXCL12 chemotaxis.
Glioblastoma (GBM), characterized by high infiltrative capacity, is the most common and deadly type of primary brain tumor in adults. GBM cells, including therapy-resistant glioblastoma stem-like cells (GSCs), invade the healthy brain parenchyma to form secondary tumors even after patients undergo surgical resection and chemoradiotherapy. New techniques are therefore urgently needed to eradicate these residual tumor cells. A thiol-Michael addition injectable hydrogel for compatibility with GBM therapy is previously characterized and optimized. This study aims to develop the hydrogel further to capture GBM/GSCs through CXCL12-mediated chemotaxis. The release kinetics of hydrogel payloads are investigated, migration and invasion assays in response to chemoattractants are performed, and the GBM-hydrogel interactions in vitro are studied. With a novel dual-layer hydrogel platform, it is demonstrated that CXCL12 released from the synthetic hydrogel can induce the migration of U251 GBM cells and GSCs from the extracellular matrix microenvironment and promote invasion into the synthetic hydrogel via amoeboid migration. The survival of GBM cells entrapped deep into the synthetic hydrogel is limited, while live cells near the surface reinforce the hydrogel through fibronectin deposition. This synthetic hydrogel, therefore, demonstrates a promising method to attract and capture migratory GBM cells and GSCs responsive to CXCL12 chemotaxis.

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