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

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dc.contributor.authorKhan, Zerin Mahzabinen
dc.contributor.authorMunson, Jennifer M.en
dc.contributor.authorLong, Timothy E.en
dc.contributor.authorVlaisavljevich, Elien
dc.contributor.authorVerbridge, Scott S.en
dc.date.accessioned2023-08-15T14:43:05Zen
dc.date.available2023-08-15T14:43:05Zen
dc.date.issued2023-06en
dc.description.abstractGlioblastoma (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.en
dc.description.notesThis research was funded by the NSF CAREER Award [Grant CBET-1652112] (SSV), NSERC Postgraduate Doctoral Scholar Award (ZMK), P.E.O. Scholar Award (ZMK), and Virginia Tech Graduate Research Development Program grant (ZMK). The authors would like to acknowledge Yanping Liang for culturing the G34 and G528 cells, Dr. Kinsley Tate for technical training on synthesizing the collagen-HA hydrogels, Dr. Caleb Stine for guidance on setting the parameters for reflectance imaging on the multiphoton microscope, and Dr. Rosalyn Hatlen for guidance on setting the parameters for second harmonic generation on the multiphoton microscope. The authors thank Dr. Rafael Davalos for access to the BTX electro square porator and acknowledge Zaid Salameh and Raffae Ahmad for technical training on using the BTX electro square porator. Graphical abstract was designed with BioRender.com.en
dc.description.sponsorshipNSF CAREER Award [CBET-1652112]; NSERC Postgraduate Doctoral Scholar Award; P.E.O. Scholar Award; Virginia Tech Graduate Research Development Programen
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1002/adhm.202300671en
dc.identifier.eissn2192-2659en
dc.identifier.issn2192-2640en
dc.identifier.issue14en
dc.identifier.pmid37014179en
dc.identifier.urihttp://hdl.handle.net/10919/116041en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherWileyen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectcell migrationen
dc.subjectcollagen-hyaluronic acid hydrogelen
dc.subjectcontrolled deliveryen
dc.subjectCXCL12 chemotaxisen
dc.subjectglioblastoma cellsen
dc.subjectglioblastoma stem-like cellsen
dc.subjectthiol-Michael addition hydrogelen
dc.titleDevelopment of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem-Like Cells with CXCL12-Mediated Chemotaxisen
dc.title.serialAdvanced Healthcare Materialsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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