Regulation of cell signaling and function via changes in growth factor presentation

The ability to control cell migration has significance in virtually all areas of wound repair and regeneration, and the creation of biomaterials that actively control the migration rate and direction of cells has implications for both the clinic and basic science. In this work, we describe the covalent modification of materials with immobilized growth factor in order to: 1) explore how growth factor presentation impacts cellular response to materials, and 2) pursue the development of bioactive, growth factor-modified materials for dermal wound healing. Specifically, we have cultured human keratinocytes in the presence of epidermal growth factor (EGF) in a soluble form, tethered in a homogeneous pattern, or tethered in a gradient pattern, followed by analysis of cellular signaling, proliferation, and migration in response to these EGF cues. Keratinocyte migration was strongly dependent upon EGF presentation, with soluble EGF eliciting a strong proliferative response and tethered EGF eliciting a strong migratory response. The greatest acceleration of keratinocyte migration was achieved using gradients of immobilized EGF. Such acceleration of cell migration may have a significant impact on the development of treatments to enable faster, more cost-effective wound repair in many different types of tissues. Moreover, better understanding the interaction of cells with soluble vs. immobilized growth factors can help us to elucidate native healing events and achieve greater control over cell function.