Effect of collagen gel stiffness on neurite extension

Although collagen is commonly used as components of tissue-engineered nerve-guidance channels, little is known about the effect of the mechanical properties of commonly used gel concentrations on the extension of neurites. This study focused on neurite extension of dissociated chick dorsal root ganglia in vitro over a range of collagen concentrations (0.4-2.0 mg/ml). Neurite length increased in all gels between day 1 and day 4, except at the highest collagen concentration, where a 9% decrease was noted at day 4. Although maximum neurite extension was seen in lower concentration gels (0.6-0.8 mg/ml), mechanical stiffness of each gel significantly increased with increasing concentration, from 2.2 Pa at 0.4 mg/ml to 17.0 Pa at 2.0 mg/ml. A previous model of mechanical stiffness versus neurite outgrowth did not fit this data well, likely because of interactions between the growth cone and the collagen fibers. Overall, these results provided insight regarding factors that influence neurite elongation and may be utilized to further optimize tissue-engineered scaffolds.