Characterization and structure-property relationships of an injectable thiol-Michael addition hydrogel toward compatibility with glioblastoma therapy

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dc.contributor.authorKhan, Zerin Mahzabinen
dc.contributor.authorWilts, Emilyen
dc.contributor.authorVlaisavljevich, Elien
dc.contributor.authorLong, Timothy E.en
dc.contributor.authorVerbridge, Scott S.en
dc.date.accessioned2022-09-12T12:00:20Zen
dc.date.available2022-09-12T12:00:20Zen
dc.date.issued2022-05-01en
dc.date.updated2022-09-10T19:52:39Zen
dc.description.abstractGlioblastoma multiforme (GBM) is an aggressive primary brain cancer and although patients undergo surgery and chemoradiotherapy, residual cancer cells still migrate to healthy brain tissue and lead to tumor relapse after treatment. New therapeutic strategies are therefore urgently needed to better mitigate this tumor recurrence. To address this need, we envision after surgical removal of the tumor, implantable biomaterials in the resection cavity can treat or collect residual GBM cells for their subsequent eradication. To this end, we systematically characterized a poly(ethylene glycol)-based injectable hydrogel crosslinked via a thiol-Michael addition reaction by tuning its hydration level and aqueous NaHCO3 concentration. The physical and chemical properties of the different formulations were investigated by assessing the strength and stability of the polymer networks and their swelling behavior. The hydrogel biocompatibility was assessed by performing in vitro cytotoxicity assays, immunoassays, and immunocytochemistry to monitor the reactivity of astrocytes cultured on the hydrogel surface over time. These characterization studies revealed key structure-property relationships. Furthermore, the results indicated hydrogels synthesized with 0.175 M NaHCO3 and 50 wt% water content swelled the least, possessed a storage modulus that can withstand high intracranial pressures while avoiding a mechanical mismatch, had a sufficiently crosslinked polymer network, and did not degrade rapidly. This formulation was not cytotoxic to astrocytes and produced minimal immunogenic responses in vitro. These properties suggest this hydrogel formulation is the most optimal for implantation in the resection cavity and compatible toward GBM therapy. Statement of significance: Survival times for glioblastoma patients have not improved significantly over the last several decades, as cancer cells remain after conventional therapies and form secondary tumors. We characterized a biodegradable, injectable hydrogel to reveal structure-property relationships that can be tuned to conform the hydrogel toward glioblastoma therapy. Nine formulations were systematically characterized to optimize the hydrogel based on physical, chemical, and biological compatibility with the glioblastoma microenvironment. This hydrogel can potentially be used for adjuvant therapy to glioblastoma treatment, such as by providing a source of molecular release for therapeutic agents, which will be investigated in future work. The optimized formulation will be developed further to capture and eradicate glioblastoma cells with chemical and physical stimuli in future research.en
dc.description.versionAccepted versionen
dc.format.extentPages 266-278en
dc.format.extent13 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.actbio.2022.03.016en
dc.identifier.eissn1878-7568en
dc.identifier.issn1742-7061en
dc.identifier.orcidVerbridge, Scott [0000-0002-4074-8799]en
dc.identifier.orcidVlaisavljevich, Eli [0000-0002-4097-6257]en
dc.identifier.otherS1742-7061(22)00148-9 (PII)en
dc.identifier.pmid35296443en
dc.identifier.urihttp://hdl.handle.net/10919/111792en
dc.identifier.volume144en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000799778200009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectEngineering, Biomedicalen
dc.subjectMaterials Science, Biomaterialsen
dc.subjectGlioblastomaen
dc.subjectAstrocytesen
dc.subjectThiol-Michael additionen
dc.subjectInjectable hydrogelen
dc.subjectCharacterizationen
dc.subjectBRAINen
dc.subjectBEHAVIORen
dc.subjectHYALURONANen
dc.subjectMIGRATIONen
dc.subjectDELIVERYen
dc.subjectMATRIXen
dc.subjectCELLSen
dc.subjectFLOWen
dc.subjectSTEMen
dc.subjectBioengineeringen
dc.subjectBrain Disordersen
dc.subjectBrain Canceren
dc.subjectRare Diseasesen
dc.subjectCanceren
dc.subjectNeurosciencesen
dc.subjectOrphan Drugen
dc.subject.meshHumansen
dc.subject.meshGlioblastomaen
dc.subject.meshNeoplasm Recurrence, Localen
dc.subject.meshSulfhydryl Compoundsen
dc.subject.meshPolymersen
dc.subject.meshBiocompatible Materialsen
dc.subject.meshHydrogelsen
dc.subject.meshTumor Microenvironmenten
dc.titleCharacterization and structure-property relationships of an injectable thiol-Michael addition hydrogel toward compatibility with glioblastoma therapyen
dc.title.serialActa Biomaterialiaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2022-03-08en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Engineeringen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/Engineering/Biomedical Engineering and Mechanicsen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Engineering/COE T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten
pubs.organisational-group/Virginia Tech/Graduate studentsen
pubs.organisational-group/Virginia Tech/Graduate students/Doctoral studentsen

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