title: Thermoresponsive Copolypeptide Hydrogel Vehicles for Central Nervous System Cell Delivery.
abstract: Biomaterial vehicles have the potential to facilitate cell transplantation in the central nervous system (CNS). We have previously shown that highly tunable ionic diblock copolypeptide hydrogels (DCH) can provide sustained release of hydrophilic and hydrophobic molecules in the CNS. Here, we show that recently developed non-ionic and thermoresponsive DCH called DCHTexhibit excellent cytocompatibility. Neural stem cell (NSC) suspensions in DCHTwere easily injected as liquids at room temperature. DCHTwith a viscosity tuned to prevent cell sedimentation and clumping significantly increased the survival of NSC passed through injection cannulae. At body temperature, DCHTself-assembled into hydrogels with a stiffness tuned to that of CNS tissue. After injectionin vivo, DCHTsignificantly increased by three-fold the survival of NSC grafted into healthy CNS. In injured CNS, NSC injected as suspensions in DCHTdistributed well in non-neural lesion cores, integrated with healthy neural cells at lesion perimeters and supported regrowing host nerve fibers. Our findings show that non-ionic DCHThave numerous advantageous properties that make them useful tools forin vivodelivery of cells and molecules in the CNS for experimental investigations and potential therapeutic strategies.
authors.affiliation: Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles CA 90095-1569, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Burda
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Anderson
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ao
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Yin
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles CA 90095-1569, USA; Department of Bioengineering, University of California Los Angeles, Los Angeles CA 90095-1600, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Deming
authors.affiliation: Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles CA 90095-1763, USA.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
keywords: Biomaterials; brain; drug delivery; hydrogel; neural stem cells; spinal cord; transplantation