Biological Methods for Enhancing Wound Healing Properties

描述（由申请人提供）：慢性伤口和溃疡随着糖尿病和相关疾病发病率的增加而增加，每年的费用超过200亿美元。这些无法愈合的伤口会导致慢性疾病、截肢和死亡，并伴有耐抗生素细菌感染。本提案旨在改善和发展这种伤口的生物治疗的新能力，蛆清创治疗（MDT）是有效的，但未被充分利用。一些种类的蛆已经进化到可以消化伤口中的液体、死组织和细菌，200多年来人们已经认识到这种改善伤口愈合的行为。大约一个世纪以来，丝光露蝇蛆一直被用于MDT。该提案旨在创造具有支持增加MDT使用特性的转基因果蝇。该提案的目标是：1)生产具有有限扩散能力的不会飞行的果蝇；2)设计更容易在伤口中观察到的荧光果蝇；3)设计促进止痛和治疗肽表达的果蝇，以改善患者的舒适度和伤口愈合。这些突变体将促进苍蝇的生产，也阻碍基因工程昆虫的逃脱。本建议的目标将支持更多地使用联合化疗，从而降低治疗费用，改善伤口愈合并限制长期使用抗生素治疗慢性伤口。

DESCRIPTION (provided by applicant): Chronic wounds and ulcers are increasing with the growing incidence of diabetes and associated illnesses and have annual costs exceeding $20 billion. These non-healing wounds result in chronic disease, limb amputations and death and are complicated by antibiotic resistant bacteria infection. This proposal seeks to improve and develop new capabilities of a biological treatment of such wounds, maggot debridement therapy (MDT) that is effective but underutilized. Some maggot species have evolved to digest fluids, dead tissues and bacteria in wounds and have been recognized for over 200 years for this improved wound healing behavior. For approximately a century, Lucilia sericata maggots have been produced for MDT. This proposal seeks to create transgenic flies with properties that will support increased use of MDT. The goals of the proposal are 1) to produce flightless flies with limited dispersal capability, 2) to engineer fluorescent flies that are more readily observed in wounds, 3) to engineer flies that facilitate analgesic and therapeutic peptide expression to improve patient comfort and wound healing. These mutants will facilitate fly production and also impede genetically engineered insect escape. The objectives of this proposal will support greater use of MDT thereby reducing treatment costs, improving wound healing and limiting the persistent use of antibiotics for treating chronic wounds.