Biomaterials Presenting Antimicrobial Peptides

呈现抗菌肽的生物材料

• 批准号: 0706627
• 负责人: Chengzhi Cai
• 金额: $ 33万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0706627&HistoricalAwards=false
• 关键词: Biomaterials; Presenting; Antimicrobial; Peptides

INTELLECTUAL MERIT: Antimicrobial peptides (AMPs) are small proteins found in all living systems. As a part of the innate immune system, they are potent against a broad spectrum of pathogens. Because they are derived from host tissue and have a non-specific mechanism of killing bacteria, AMPs have potential as novel pharmaceutical agents. They are often not as effective against bacteria in vitro as they are in vivo, and sometimes they are toxic to the host tissue. Here it is hypothesized that proper presentation and localization of AMPs onto biocompatible materials will increase their potency against pathogens and limit toxicity toward host cells in vitro. The objectives are to develop nanoscale-patterned surfaces presenting AMPs and to use these systems to quantify the antimicrobial activity and host cell toxicity in response to AMP presentation. A further objective is to modify collagen, currently in wide use as a biocompatible surface coating, with AMPs. The broader objective is to create biomaterials that mimic the in vivo presentation of AMPs to pathogens. The focus is on three AMPs expressed by human ocular surface epithelia. These species will be attached to biocompatible materials with control over density, spacing, and nanoscale patterning to investigate the effect of local AMP concentration and patterning on microbiocidal activity and corneal epithelial cell toxicity. The proposed research capitalizes on a new means of precisely controlling the presentation of AMPs on a size scare not previously available. It will allow quantification of microbiocidal effectiveness and host cell toxicity in response to nanoscale presentation of AMPs. BROADER IMPACTS: The proposed work is aimed directly at improvements in contact lens fabrication to inhibit eye infections. In addition to these and other novel antimicrobial devices that might emerge from this work, the project will yield new fundamental insights into the mechanism by which AMPs disrupt the bacterial membrane and the role of AMP concentration and cooperativity in determining their activity. The research program will provide interdisciplinary research experience for undergraduate, graduate, and postdoctoral level students. The PI will team with successful University of Houston minority outreach programs to Houston area high schools. He also plans to establish an undergraduate summer internship program with Texas Southern University, a historically minority university located near the University of Houston. Feeder school relationships with Xavier University, Prairie View A&M, and Texas Southern exist to provide research and educational programs accessible to women and minorities.

智力优势：抗菌肽(AMP)是存在于所有生命系统中的小蛋白质。作为先天免疫系统的一部分，它们对广泛的病原体具有很强的抵抗力。由于它们来自宿主组织，并且具有非特异性的杀菌机制，因此AMP具有作为新型药物的潜力。它们在体外对细菌的杀灭效果往往不如体内，有时对宿主组织有毒性。在这里，假设AMPs在生物相容材料上的适当呈现和定位将增加它们对病原体的效力，并在体外限制对宿主细胞的毒性。我们的目标是开发呈现AMP的纳米图案表面，并使用这些系统来量化AMP呈现的抗菌活性和宿主细胞毒性。另一个目标是用AMPS对目前广泛用作生物相容性表面涂层的胶原进行修饰。更广泛的目标是创造模拟AMP在体内呈现给病原体的生物材料。目前研究的焦点是人眼表面上皮细胞表达的三种AMP。这些物种将附着在可控制密度、间距和纳米图案的生物兼容材料上，以研究局部AMP浓度和图案对微生物杀灭活性和角膜上皮细胞毒性的影响。这项拟议的研究利用了一种新的方法来精确控制AMP的呈现，这是以前没有的尺寸恐慌。它将允许量化微生物杀灭效果和宿主细胞毒性，以响应纳米级的AMPS呈现。更广泛的影响：拟议的工作直接针对改进隐形眼镜制造以抑制眼睛感染。除了这些和其他可能从这项工作中出现的新型抗菌装置外，该项目还将对AMP破坏细菌膜的机制以及AMP浓度和协同性在确定其活性方面的作用产生新的基本见解。该研究计划将为本科生、研究生和博士后水平的学生提供跨学科的研究经验。PI将与休斯顿大学成功的少数民族推广项目合作，扩展到休斯顿地区的高中。他还计划与德克萨斯南方大学建立一个本科生暑期实习项目，这是一所历史上少数族裔的大学，位于休斯顿大学附近。与泽维尔大学、Prairie View A&Amp；M和德克萨斯南部大学建立了支线学校关系，为妇女和少数族裔提供研究和教育项目。