title: A Hydrogel Bridge Incorporating Immobilized Growth Factors and Neural Stem/Progenitor Cells to Treat Spinal Cord Injury.
abstract: Spinal cord injury (SCI) causes permanent, often complete disruption of central nervous system (CNS) function below the damaged region, leaving patients without the ability to regenerate lost tissue. To engineer new CNS tissue, a unique spinal cord bridge is created to deliver stem cells and guide their organization and development with site-specifically immobilized growth factors. In this study, this bridge is tested, consisting of adult neural stem/progenitor cells contained within a methacrylamide chitosan (MAC) hydrogel and protected by a chitosan conduit. Interferon-γ (IFN-γ) and platelet-derived growth factor-AA (PDGF-AA) are recombinantly produced and tagged with an N-terminal biotin. They are immobilized to streptavidin-functionalized MAC to induce either neuronal or oligodendrocytic lineages, respectively. These bridges are tested in a rat hemisection model of SCI between T8 and T9. After eight weeks treatments including chitosan conduits result in a significant reduction in lesion area and macrophage infiltration around the lesion site (p < 0.0001). Importantly, neither immobilized IFN-γ nor PDGF-AA increased macrophage infiltration. Retrograde tracing demonstrates improved neuronal regeneration through the use of immobilized growth factors. Immunohistochemistry staining demonstrates that immobilized growth factors are effective in differentiating encapsulated cells into their anticipated lineages within the hydrogel, while qualitatively reducing glial fibrillary acid protein expression.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Whitby Hall 211, Akron, OH, 44325, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, The University of Akron, Auburn Science and Engineering Center, 275 West Tower, Akron, OH, 44325, USA.
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Ham
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Whitby Hall 211, Akron, OH, 44325, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Neill
authors.affiliation: Department of Biology, The University of Akron, Auburn Science and Engineering Center D401, Akron, OH, 44325, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Farrag
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Whitby Hall 211, Akron, OH, 44325, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Mohrman
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Whitby Hall 211, Akron, OH, 44325, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Koenig
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Akron, Whitby Hall 211, Akron, OH, 44325, USA.|Department of Biomedical Engineering, The University of Akron, Auburn Science and Engineering Center, 275 West Tower, Akron, OH, 44325, USA.
authors.forename: Nic D
authors.initials: ND
authors.lastname: Leipzig
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D055767:Immobilized Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D007109:Immunity / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D013266:Stilbamidines / Q000737:chemistry
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D055767:Immobilized Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D013266:Stilbamidines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
keywords: hemisections; hydrogel scaffolds; immobilized growth factors; neural stem/progenitor cells; spinal cord injuries