Adhesive and mechanical properties of hydrogels influence neurite extension

Photopolymerizable polyethylene glycol (PEG) hydrogels conjugated with bioactive ligands were examined for their use as scaffolds in peripheral nerve regeneration applications. The bioactivity and mechanical properties of PEG hydrogels can be tailored through the integration of bioactive factors (adhesion ligands, proteolytic sites, growth factors) and the alteration of PEG concentrations, respectively. For peripheral nerve regeneration, it will be important to determine the type and concentration of the bioactive molecules required to improve neurite extension. In this study, cell adhesion ligands (RGDS, IKVAV, and YIGSR) were covalently attached to PEG hydrogels. Both the type and concentration of cell adhesion ligand used affected neurite extension. Extension from PC12 cells was greater on hydrogels with RGDS incorporated than IKVAV, and the optimal concentration for each ligand was different. Cells adhered to but did not extend neurites on hydrogels with YIGSR. Cells did not adhere to hydrogels containing RGES. Furthermore, different combinations of these ligands affected neurite extension to different degrees. The mechanical properties of the hydrogels also significantly affected neurite extension. PC12 cells grown on more flexible hydrogels exhibited the greatest degree of neurite extension. PEG hydrogels have thus been developed with varying biochemical and mechanical properties that may enhance nerve regeneration.