There exists an obvious clinical need for materials that enhance epidermal wound closure, as over 5 million Americans have chronic wounds, costing $16 billion/year to treat. Stimulation of keratinocyte migration has the potential to enhance or accelerate dermal wound healing through restoration of wound surface integrity. Accelerated wound closure not only reduces patient suffering and the cost of treatment, but may also result in reduced scar formation. Many current therapies utilize growth factor-containing materials for the enhancement of wound healing. However, a gradient-patterned growth factor may be capable of not only stimulating cell migration, but also regulating cell migration speed and direction. Synthesis of such a system would enable more precise control over wound healing and represent a major advance in tissue repair technology. The specific hypothesis driving the proposed research is that the rate and direction of keratinocyte migration can be controlled via micropatterned gradients of epidermal growth factor (EGF). EGF plays a critical role in wound healing and has previously been shown to display enhanced biological efficacy following surface-immobilization. To provide a comprehensive analysis of the interactions of keratinocytes with EGF, we have designed the following Specific Aims.
Aim 1 will entail investigation of keratinocyte migration on 2-D gradient patterns of EGF formed via photolithographic techniques, paying specific attention to: a) evaluation of the effects of changing EGF pattern gradient density on cell migration speed and direction, and b) characterization of the expression of biological factors relevant to cell function and migration in response to cellular interaction with patterned EGF.
In Aim 2, patterning combinations of other migration-inducing growth factors or extracellular matrix components will be explored with the goal of optimizing the directed migration platform and achieving synergistic increases in cell migration. Lastly, Aim 3 addresses translation of the knowledge gained from these 2-D directed migration systems to the development of 3-D matrices. The proposed directed migration system is innovative and has the potential to make a widespread and significant clinical impact through the creation of materials that promote regeneration of many types of tissues. ? ? ?
| Puccinelli, Tracy J; Bertics, Paul J; Masters, Kristyn S (2010) Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation. Acta Biomater 6:3415-25 |
| Lee, Myung-Ryul; Stahl, Shannon S; Gellman, Samuel H et al. (2009) Nylon-3 copolymers that generate cell-adhesive surfaces identified by library screening. J Am Chem Soc 131:16779-89 |
| Stefonek-Puccinelli, Tracy Jane; Masters, Kristyn S (2008) Co-immobilization of gradient-patterned growth factors for directed cell migration. Ann Biomed Eng 36:2121-33 |
| Stefonek, Tracy Jane; Masters, Kristyn S (2007) Immobilized gradients of epidermal growth factor promote accelerated and directed keratinocyte migration. Wound Repair Regen 15:847-55 |
