Polyethylene glycol (PEG) is a widely used polymer for biomedical applications because of good biocompatibility, non-immunogenicity, and tunable mechanical properties. Recently we have developed a photo-polymerizable poly-L-lysine (PLL) that can be covalently incorporated into PEG diacrylate (PEGDA) hydrogels to improve their bioactivity by providing both positive charges and cell binding sites. 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 amount of pendent PLL chains in the hydrogels by photo-crosslinking PEGDA with weight compositions of PLL (fPLL) 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, proliferation, and differentiation. The amount of actually grafted PLL and charge densities were characterized, showing a proportional increase with the feed composition fPLL. NPC viability in 3D hydrogels was significantly improved in a PLL grafting density-dependent manner at days 7 and 14 post-encapsulation. Similarly, NPC proliferation was promoted on the PLL-grafted hydrogels with increasing fPLL up to 2%. More intriguingly, NPC lineage commitment was dramatically altered by the amount of grafted PLL chains in the hydrogels. NPC differentiation elicited a parabolic or non-monotonic dependence on fPLL, resulting in cells mostly differentiated toward mature neurons with extensive neurite formation on the PLL-grafted hydrogels with fPLL of 2%, whereas the neutral hydrogels and PLL-grafted hydrogels with higher fPLL of 5% provided less support for NPC differentiation. These results demonstrated that PLL-grafted hydrogels with an optimal fPLL of 2% could be a promising cell carrier that promoted NPC functions for treatment of nerve injuries.

Optimal poly(L-lysine) grafting density in hydrogels for promoting neural progenitor cell functions

244th National Meeting (2012)

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