Optimal Poly(l-lysine) Grafting Density in Hydrogels for Promoting Neural Progenitor Cell Functions

• Published in: Biomacromolecules Vol. 13; no. 5; pp. 1663 - 1674
• Main Authors: Cai, Lei, Lu, Jie, Sheen, Volney, Wang, Shanfeng
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14.05.2012
• Subjects: Animals; Applied sciences; Biological and medical sciences; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Exact sciences and technology; Hydrogels - chemistry; Hydrogels - pharmacology; Medical sciences; Mice; Models, Molecular; Molecular Structure; Neural Stem Cells - cytology; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Physicochemistry of polymers; Polyethylene Glycols - chemistry; Polylysine - chemistry; Polylysine - pharmacology; Polymerization; Polymers and radiations; Structure-Activity Relationship; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Biological properties; Encapsulation; Cell proliferation; Viscoelasticity; Graft copolymer; Property composition relationship; Aminoacid copolymer; Lysine polymer; Macromer; Ethylene oxide polymer; Colloidal gel; Cell adhesion; Electrokinetic potential; Acrylate copolymer; Biomaterial; Framework; Photochemical copolymerization; Swelling; Tissue engineering; Cell differentiation; Ethylene oxide copolymer; Experimental study; Gene expression; Neuron; Preparation; Allylic derivative copolymer; Prepolymer; Lysine copolymer; Nervous tissue; Progenitor cell
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm300381d

Recently, we have developed a photopolymerizable poly(l-lysine) (PLL) that can be covalently incorporated into poly(ethylene glycol) diacrylate (PEGDA) hydrogels to improve their bioactivity by providing positive charges. To explore the potential of these PLL-grafted PEGDA hydrogels as a cell delivery vehicle and luminal filler in nerve guidance conduits for peripheral and central nerve regeneration, we varied the number of pendent PLL chains in the hydrogels by photo-cross-linking PEGDA with weight compositions of PLL (ϕPLL) of 0, 1, 2, 3, and 5%. We further investigated the effect of PLL grafting density on E14 mouse neural progenitor cell (NPC) behavior including cell viability, attachment, proliferation, differentiation, and gene expression. The amount of actually grafted PLL and charge densities were characterized, showing a proportional increase with the feed composition ϕPLL. NPC viability in 3D hydrogels was significantly improved in a PLL grafting density-dependent manner at days 7 and 14 postencapsulation. Similarly, NPC attachment and proliferation were promoted on the PLL-grafted hydrogels with increasing ϕPLL up to 2%. More intriguingly, NPC lineage commitment was dramatically altered by the amount of grafted PLL chains in the hydrogels. NPC differentiation demonstrated a parabolic or nonmonotonic dependence on ϕPLL, resulting in cells mostly differentiated toward mature neurons with extensive neurite formation and astrocytes rather than oligodendrocytes on the PLL-grafted hydrogels with ϕPLL of 2%, whereas the neutral hydrogels and PLL-grafted hydrogels with higher ϕPLL of 5% support NPC differentiation less. Gene expression of lineage markers further illustrated this trend, indicating that PLL-grafted hydrogels with an optimal ϕPLL of 2% could be a promising cell carrier that promoted NPC functions for treatment of nerve injuries.