No abstract

Central nervous system (CNS) injuries and diseases result in neuronal damage and loss of function. Transplantation of neural stem cells (NSCs) has been shown to improve locomotor function after transplantation. However, due to the immune and inflammatory response at the injury site, the survival rate of the engrafted cells is low. Engrafted cell viability has been shown to increase when transplanted within a hydrogel. Hyaluronic acid (HA) hydrogels have natural anti-inflammatory properties and the backbone can be modified to introduce bioactive agents, such as anti-Fas, which we have previously shown to promote NSC survival while suppressing immune cell activity in bulk hydrogels in vitro. Although bulk HA hydrogels have shown to promote stem cell survival, microsphere gels for NSC encapsulation and delivery may have additional advantages. In this study, a flow-focusing microfluidic device was used to fabricate either vinyl sulfone-modified HA (VS-HA) or anti-Fas-conjugated HA (anti-Fas HA) microsphere gels encapsulated with NSCs. The majority of encapsulated NSCs remained viable for at least 24 h in the VS-HA and anti-Fas HA microsphere gels. Moreover, T-cells cultured in suspension with the anti-Fas HA microsphere gels had reduced viability after contact with the microsphere gels compared to the media control and soluble anti-Fas conditions. This approach can be adapted to encapsulate various cell types for therapeutic strategies in other physiological systems in order to increase survival by reducing the immune response. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 608-618, 2017.

A one-step Michael addition click chemistry reaction is used to fabricate a bioactive conjugated hyaluronic acid (HA) scaffold for neural engineering applications.

Polyelectrolyte multilayers (PEMs) are of great interest as cell culture surfaces because of their ability to modify topography and surface energy and release biologically relevant molecules such as growth factors. In this work, fibroblast growth factor 2 (FGF2) was adsorbed directly onto polystyrene, plasma-treated polystyrene, and glass surfaces with a poly(methacrylic acid) and poly-l-histidine PEM assembled above it. Up to 14 ng/cm of FGF2 could be released from plasma-treated polystyrene surfaces over the course of 7 days with an FGF2 solution concentration of 100 μg/mL applied during the adsorption process. This release rate could be modulated by adjusting the adsorption concentration, decreasing to as low as 2 ng/cm total release over 7 days using a 12.5 μg/mL FGF2 solution. The surface energy and roughness could also be regulated using the adsorbed PEM. These properties were found to be substrate- and first-layer-dependent, supporting current theories of PEM assembly. When released, FGF2 from the PEMs was found to significantly enhance fibroblast proliferation as compared to culture conditions without FGF2. The results showed that growth factor release profiles and surface properties are easily controllable through modification of the PEM assembly steps and that these strategies can be effectively applied to common cell culture surfaces to control the cell fate.

Common characterisation methods for cell-derived extracellular matrices (ECMs) are compared using both unmodified and azide-bearing fibroblast-derived ECM.