Micropatterned EGF of Accelerated Wound Healing

描述（由申请人提供）：由于超过500万美国人患有慢性伤口，每年花费160亿美元治疗慢性伤口，因此对增强表皮伤口闭合的材料存在明显的临床需求。刺激角质细胞迁移有可能通过恢复创面完整性来增强或加速皮肤伤口愈合。加速伤口愈合不仅可以减少患者的痛苦和治疗费用，而且还可以减少疤痕的形成。目前许多治疗方法利用含有生长因子的材料来促进伤口愈合。然而，梯度模式生长因子可能不仅能够刺激细胞迁移，而且能够调节细胞迁移的速度和方向。这种系统的合成将能够更精确地控制伤口愈合，并代表了组织修复技术的重大进步。推动该研究的具体假设是，角质形成细胞迁移的速度和方向可以通过表皮生长因子（EGF）的微模式梯度来控制。EGF在伤口愈合中起着至关重要的作用，并且在表面固定后显示出增强的生物功效。为了全面分析角质形成细胞与表皮生长因子的相互作用，我们设计了以下具体目标。目标1将需要研究角质细胞在通过光刻技术形成的EGF的二维梯度模式上的迁移，特别关注：a)评估改变EGF模式梯度密度对细胞迁移速度和方向的影响，以及b)表征细胞与模式EGF相互作用时与细胞功能和迁移相关的生物因子的表达。在Aim 2中，将探索其他诱导迁移的生长因子或细胞外基质成分的组合模式，以优化定向迁移平台并实现细胞迁移的协同增加。最后，Aim 3将从这些二维定向迁移系统中获得的知识转化为三维矩阵的开发。提出的定向迁移系统是创新的，并且有潜力通过创造促进多种组织再生的材料来产生广泛而重要的临床影响。

DESCRIPTION (provided by applicant): 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.