Hydrogel/electrospun fiber composites influence neural stem/progenitor cell fate

Cell replacement therapy with multi-potent neural stem/progenitor cells (NSPCs) into the injured spinal cord is limited by poor survival and host tissue integration. An injectable and biocompatible polymeric cell delivery system serves as a promising strategy to facilitate cell delivery, promote cell survival and direct cell behaviour. We developed and characterized the use of a physical hydrogel blend of hyaluronan (HA) and methylcellulose (MC) for NSPC delivery, and incorporated electrospun fibers of either collagen or poly(3-caprolactone-co-D,L-lactide) (P(CL:DLLA)) to promote cell–matrix interactions and influence cell behaviour. The shear-thinning and thermally reversible HAMC had a zero-shear viscosity of 1.2 Pa s at 25 C, formed a weak gel at 37 C with a yield stress of 0.5 Pa, and swelled to 115% of its original volume after one day. HAMC was both cytocompatible and allowed NSPC differentiation in vitro, similar to what one would observe in media. Interestingly, cells cultured in HAMC remained homogeneously dispersed over the 7 d culture period, unlike those cultured in media controls where significant cell aggregation was observed. Inclusion of electrospun fibers in the HAMC hydrogel further influenced cell behaviour. Composite systems of collagen fibers in HAMC resulted in reduced survival/proliferation and differentiation relative to HAMC itself whereas composites of P(CL:DLLA) fibers in HAMC maintained cell survival/proliferation and enhanced neuronal and oligodendrocytic differentiation similar to HAMC. In this study, the importance of the cell delivery vehicle to NSPC survival and cell fate was demonstrated in vitro and is being tested in ongoing studies in vivo.