A macroporous hydrogel for the coculture of neural progenitor and endothelial cells to form functional vascular networks in vivo

Abstract

A microvascular network is critical for the survival and function of most tissues. We have investigated the potential of neural progenitor cells to augment the formation and stabilization of microvascular networks in a previously uncharacterized three-dimensional macroporous hydrogel and the ability of this engineered system to develop a functional microcirculation in vivo. The hydrogel is synthesized by cross-linking polyethylene glycol with polylysine around a salt-leached polylactic-co-glycolic acid scaffold that is degraded in a sodium hydroxide solution. An open macroporous network is formed that supports the efficient formation of tubular structures by brain endothelial cells. After subcutaneous implantation of hydrogel cocultures in mice, blood flow in new microvessels was apparent at 2 weeks with perfused networks established on the surface of implants at 6 weeks. Compared to endothelial cells cultured alone, cocultures of endothelial cells and neural progenitor cells had a significantly greater density of tubular structures positive for platelet endothelial cell adhesion molecule-1 at the 6-week time point. In implant cross sections, the presence of red blood cells in vessel lumens confirmed a functional microcirculation. These findings indicate that neural progenitor cells promote the formation of endothelial cell tubes in coculture and the development of a functional microcirculation in vivo. We demonstrate a previously undescribed strategy for creating stable microvascular networks to support engineered tissues of desired parenchymal cell origin.

Getting the right stuff: Controlling neural stem cell state and fate in vivo and in vitro with biomaterials

“…The width of the fibers did not affect the alignment response but NSCs proliferated more on nano-than on micro-scale fibers. Polyethylene glycol (PEG) alone [41] or in combination with polylysine [42] also supported the culture of NSCs. NSC progression from proliferation to neuronal differentiation and formation of functional synapses was reported for NSCs interdispersed in Type I collagen [43].…”

Biomaterials for the central nervous system

“…The hydrogel was seeded with brain endothelial cells and neural progenitor cells and implanted subcutaneously into mice. Functional microvascular network was formed in the hydrogel, which is critical to support engineered tissue replacement (Ford et al 2006).…”

Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype

“…[35], 2.3.3. Hydrogel mesh size-PEGDA hydrogel mesh size cannot be visualized using standard techniques such as scanning electron microscopy (SEM) [36]. Thus, a variety of methods to estimate PEGDA hydrogel mesh size have been developed, including correlations linking measurable quantities, such as equilibrium hydrogel swelling, to mesh size [34,37].…”