Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

Abstract

Poly(ethylene glycol) (PEG) hydrogels are being developed as cell delivery vehicles that have great potential to improve neuronal replacement therapies. Current research priorities include (1) characterizing neural cell growth within PEG hydrogels relative to standard culture systems and (2) generating neuronal-enriched populations within the PEG hydrogel environment. This study compares the percentage of neural precursor cells (NPCs), neurons, and glia present when dissociated neural cells are seeded within PEG hydrogels relative to standard monolayer culture. Results demonstrate that PEG hydrogels enriched the initial cell population for NPCs, which subsequently gave rise to neurons, then to glia. Relative to monolayer culture, PEG hydrogels maintained an increased percentage of NPCs and a decreased percentage of glia. This neurogenic advantage of PEG hydrogels is accentuated in the presence of basic fibroblast growth factor and epidermal growth factor, which more potently increase NPC and neuronal expression markers when applied to cells cultured within PEG hydrogels. Finally, this work demonstrates that glial differentiation can be selectively eliminated upon supplementation with a g-secretase inhibitor. Together, this study furthers our understanding of how the PEG hydrogel environment influences neural cell composition and also describes select soluble factors that are useful in generating neuronal-enriched populations within the PEG hydrogel environment.

Monodisperse polyethylene glycol diacrylate hydrogel microsphere formation by oxygen-controlled photopolymerization in a microfluidic device

“…Over a certain polymer composition range, highly water-swollen PEGDA hydrogel networks have been proven to be cytocompatible encapsulants for many cell types including fibroblasts 13 , chondrocytes 14 , vascular smooth muscle cells (SMCs) 15 , endothelial cells (ECs) 16 , osteoblasts 17 , neural cells 18 , and stem cells 19 . Synthetic customization of PEGDA macromolecular architecture and chemistry provides a broad diversity of properties, making it an attractive alternative to natural hydrogels.…”

Silk Hydrogels as Soft Substrates for Neural Tissue Engineering

“…Here, we sought materials of controllable biomechanics that could be formed under non‐toxic conditions. Although polyethylene glycol (PEG) hydrogels are frequently suggested for cell encapsulation and are non‐toxic, it has been found that neuronal cell cultures in PEG hydrogels experienced initial cell death within 1 day of culture and did not exhibit greater viability or proliferation as compared to monolayer controls, even when supplemented with soluble growth factors 45. Natural biomaterials that have been explored for neural cell culture include collagen,46 Matrigel,2 alginate,47 agarose,48 and fibrin 49.…”

Development and characterization of polyethylene glycol–carbon nanotube hydrogel composite

“…9 Not surprisingly, various CNT-hydrogel composites have been developed, including both natural and synthetic polymers such as polyacrylamide, 15 polymethacrylic acid, 16 polysaccharides, 17 gelatin, 18,19 collagen, 6,20 and PEG 3, 13 among others. 21 Furthermore, PEG hydrogels have shown promise as neural and neural stem cell scaffolds 22,23 or neural cell delivery vehicles, 24 CNT-PEG-acrylate hydrogels have shown excellent promise as neural electrode coatings, 13,25 and PEGfunctionalized CNTs have been shown to promote neural regeneration. 21 Furthermore, PEG hydrogels have shown promise as neural and neural stem cell scaffolds 22,23 or neural cell delivery vehicles, 24 CNT-PEG-acrylate hydrogels have shown excellent promise as neural electrode coatings, 13,25 and PEGfunctionalized CNTs have been shown to promote neural regeneration.…”