Photopolymerizable nanoarray hydrogels deliver CNTF and promote differentiation of neural stem cells

Abstract

One of the goals in neural tissue engineering is to be able to direct the repair and replacement of lost cells and tissue. This will likely involve a multifactorial approach that combines cells, an appropriate scaffold, and drug delivery. In many cases, this system will also need to be able to be delivered in a minimally invasive manner. To address these needs, we have developed a new nanoarray scaffold that can deliver a growth factor over a few weeks, is photopolymerizable to permit minimally invasive administration, and supports the encapsulation, migration, and differentiation of cells. As a model system, we have focused on delivering ciliary neurotrophic factor (CNTF) and neural stem cells (NSCs). CNTF has been shown to be neuroprotective in the central nervous system and also directs NSCs to differentiate, suggesting that it may be useful in treating or engineering tissues of the nervous system. However, combining CNTF delivery with a scaffold to support the growth of neural cells and tissue has been challenging. Here CNTF-loaded nanospheres based on poly(D,L-lactic-co-glycolic acid) (PLGA) were surface-modified with acrylated poly(ethylene glycol) (PEG) and crosslinked into a photopolymerizable poly-L-lysine/PEG hydrogel to act as both a tissue engineering scaffold and a drug delivery system. When NSCs were encapsulated in this CNTF-loaded construct, we observed high survival rates and significant differentiation to mature phenotypes. This allows us to tailor the microenvironment to engineer tissues in new ways.