Immobilized gradients of epidermal growth factor promote accelerated and directed keratinocyte migration

Abstract

Acceleration of wound closure results not only in decreased patient suffering and cost of wound treatment, but may also minimize scarring and lead to formation of a more stable closed wound. Cell migration is a critical element in wound healing, and it is believed that the ability to control the migration direction of cells will lead to accelerated closure of wounds. Thus, we have synthesized surfaces that are covalently modified with gradients of epidermal growth factor (EGF), a key molecule in the native wound-healing process, in order to create a platform that promotes directed cell migration. Standard photo-patterning techniques used herein enabled precise control over the spatial location of tethered EGF and the fabrication and quantitative characterization of gradient patterns of different types and slopes. Under serum-free conditions, human epidermal keratinocytes on immobilized EGF gradients preferentially migrated in the direction of higher EGF concentrations, and exhibited unidirectional migration speed and distance that was over five-fold greater than that observed on control surfaces. Treatment of migrating cells with an inhibitor of the EGF receptor resulted in immediate cessation of migration, thus verifying that the observed migration trends were directly attributable to keratinocyte interactions with immobilized EGF.