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       #Post#: 88--------------------------------------------------
       Guided NSPC differentiation in chitosan-based hydrogel scaffolds
       By: SSamani Date: February 21, 2015, 2:36 pm
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       [font=verdana][center]In vivo assessment of guided neural stem
       cell differentiation in growth factor immobilized chitosan-based
       hydrogel scaffolds
       Biomaterials 35 (2014) 9049-9057[/center]
       Abstract
       In this study, we demonstrate that a unique growth
       factor-biomaterial system can offer spatial control of growth
       factors with sustained signaling to guide the specific lineage
       commitment of neural stem/progenitor cells (NSPCs) in vivo.
       First, recombinant fusion proteins incorporating an N-terminal
       biotin tag and interferon-γ (IFN-γ), platelet derived
       growth factor-AA (PDGF-AA), or bone morphogenic protein-2
       (BMP-2) were immobilized to a methacrylamide chitosan (MAC)
       based biopolymer via a streptavidin linker to specify NSPC
       differentiation into neurons, oligodendrocytes, or astrocytes,
       respectively. MAC was mixed with growth factors (immobilized or
       adsorbed), acrylated laminin, NSPCs, and crosslinked within
       chitosan conduits. This system mimics regenerative aspects of
       the central nervous system ECM, which is largely composed of a
       crosslinked polysaccharide matrix with cell-adhesive regions,
       and adds the new functionality of protein sequestration.
       We demonstrated that these growth factors are maintained at
       functionally significant levels for 28 d in vitro. In the main
       study, immobilized treatments were compared to absorbed and
       control treatments after 28 d in vivo (rat subcutaneous).
       Masson's Trichrome staining revealed that small collagen
       capsules formed around the chitosan conduits with an average
       acceptable thickness of 153.07 ± 6.02 μm for all groups.
       ED-1 staining showed mild macrophage clustering around the
       outside of chitosan conduits in all treatments with no
       macrophage invasion into hydrogel portions. Importantly, NSPC
       differentiation staining demonstrated that immobilized growth
       factors induced the majority of cells to differentiate into the
       desired cell types as compared with adsorbed growth factor
       treatments and controls by day 28. Interestingly, immobilized
       IFN-γ resulted in neural rosette-like arrangements and even
       structures resembling neural tubes, suggesting this treatment
       can lead to guided dedifferentiation and subsequent neurulation.
       [center][size=12pt]Download link
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