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，每年治疗费用为160亿美元，因此存在对增强表皮伤口闭合的材料的明显临床需求。刺激角质形成细胞迁移具有通过恢复伤口表面完整性来增强或加速皮肤伤口愈合的潜力。加速伤口闭合不仅减少了患者的痛苦和治疗成本，而且还可以减少疤痕形成。许多目前的疗法利用含生长因子的材料来增强伤口愈合。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，并代表组织修复技术的重大进步。推动这项研究的具体假设是，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）的微图案梯度来控制。EGF在伤口愈合中起着关键作用，并且先前已显示出在表面固定后显示出增强的生物功效。为了提供角质形成细胞与EGF相互作用的全面分析，我们设计了以下具体目标。目的1将需要研究角质形成细胞迁移的2-D梯度模式的EGF形成通过EGF技术，特别注意：a）评价的影响，改变EGF模式梯度密度对细胞迁移速度和方向，和B）表征的生物因子的表达相关的细胞功能和迁移的细胞相互作用与模式的EGF。在目标2中，将探索其他迁移诱导生长因子或细胞外基质组分的模式化组合，目标是优化定向迁移平台并实现细胞迁移的协同增加。最后，目标3解决了从这些2-D定向迁移系统中获得的知识到3-D矩阵的开发的翻译。所提出的定向迁移系统是创新的，并且有可能通过创造促进多种类型组织再生的材料而产生广泛和显著的临床影响。

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.