TY - JOUR
T1 - Development of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem-Like Cells with CXCL12-Mediated Chemotaxis
AU - Khan, Zerin Mahzabin
AU - Munson, Jennifer M.
AU - Long, Timothy E.
AU - Vlaisavljevich, Eli
AU - Verbridge, Scott S.
N1 - Publisher Copyright:
© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - 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.
AB - 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.
KW - CXCL12 chemotaxis
KW - cell migration
KW - collagen-hyaluronic acid hydrogel
KW - controlled delivery
KW - glioblastoma cells
KW - glioblastoma stem-like cells
KW - thiol-Michael addition hydrogel
UR - http://www.scopus.com/inward/record.url?scp=85152940326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85152940326&partnerID=8YFLogxK
U2 - 10.1002/adhm.202300671
DO - 10.1002/adhm.202300671
M3 - Article
C2 - 37014179
AN - SCOPUS:85152940326
SN - 2192-2640
VL - 12
JO - Advanced Healthcare Materials
JF - Advanced Healthcare Materials
IS - 14
M1 - 2300671
ER -