Zero Net Charge Polymer Brush Surfaces Highly Resistant to Protein Adsorption

零净电荷聚合物刷表面高度抵抗蛋白质吸附

• 批准号: 8263028
• 负责人: K. H. Aaron Lau
• 金额: $ 5.39万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8263028
• 关键词: Adsorption; Advanced Development; Back; Behavior; Biocompatible; Biocompatible Materials; Biosensor; Blood; Body Fluids; Caliber; Cardiovascular system; Cell Adhesion; Cell Culture Techniques; Cell-Matrix Junction; Cells; Characteristics; Charge; Chemicals; Cues; Devices; Diagnostic; Electrostatics; Engineering; Ensure; Equilibrium; Event; Future; Health; Infection; Inflammation; Inflammatory Response; Intervention; Investigation; Knowledge; Lead; Length; Literature; Medical; Medical Device; Medical Students; Modification; Molecular; Molecular Structure; Outcome; Outcome Study; Patients; Performance; Plague; Plasma Proteins; Polymers; Property; Prosthesis; Proteins; Reporting; Research; Research Personnel; Research Training; Resistance; S Phase; Scientist; Series; Solid; Structure-Activity Relationship; Surface; System; Techniques; Technology; Therapeutic; Thrombosis; Tissue Engineering; Vision; adverse outcome; cost; density; design; implantable device; implanted sensor; improved; microorganism; monomer; multidisciplinary; novel; peptidomimetics; physical property; physical separation; polymerization; prevent; public health relevance; research study; sensor

DESCRIPTION (provided by applicant): The creation of durable, functional and biocompatible implants and sensors is key to improved patient outcomes and lower medical costs. Surface fouling of body-fluid-contacting devices by non-specific protein adsorption and cell attachment, and the consequent surface-induced thrombotic and inflammatory responses, degrade device performance and lead to adverse outcomes that require medical intervention. The extensive literature on surface modifications aimed at preventing bio-fouling highlights both the broad potential and the current limitations of this strategy for improving medical device and health outcomes. Recent reports have demonstrated that certain zwitterionic and ampholytic polymers are effective at inhibiting biofouling. However, a mechanistic understanding of this behavior is lacking. We hypothesize that controlling the spatial separation of oppositely charged groups within a certain length-scale smaller than the size of proteins, while maintaining the zero net charge in a polymer brush, imparts the brush surface with resistance to protein adsorption. Accordingly, this project aims to design and synthesize zero net charge polymer brushes with a range of separation between oppositely charged groups, evaluate their resistance to protein adsorption and cell adhesion, and analyze the pertinent structure-function relationships. The systematic study of the charge separation will be enabled by the solid phase synthesis of peptidomimetic polymers. This technique allows absolute control over monomer sequence, brush length and thus charge separation. This research training will be aided by the multidisciplinary profile of the investigator's research group, consisting of medical students and scientists in cell, chemical and materials engineering. The outcomes of this study will include identification of novel anti-fouling brush surfaces applicable to therapeutic and diagnostic devices, and fundamental knowledge of the configurational requirements for imparting anti-fouling properties to (pseudo)zwitterionic materials. The investigation of polymer systems possessing molecular level, sequence-specific chemical and spatial cues will advance the development of biomaterials that elicit desirable biorecognition properties. PUBLIC HEALTH RELEVANCE: This experimental study will systematically investigate the molecular structure required to confer anti-fouling properties to polymers possessing a balanced number of electrostatic charges. Coating biomedical devices with such anti-fouling polymers would prevent unwanted fouling by biomolecules and cells, which would improve device performance and patient outcomes, and lower medical costs.

描述（由申请人提供）：创建耐用，功能性和生物相容性植入物和传感器是改善患者预后和降低医疗费用的关键。通过非特异性蛋白质吸附和细胞附着以及随之而来的表面诱导的血栓形成和炎症反应，降解装置性能并导致需要医疗干预的不良后果，通过非特异性蛋白质吸附和细胞附着对身体融合的设备进行表面结垢。旨在防止生物犯规的表面修饰的广泛文献突出了这种改善医疗设备和健康成果的巨大潜力和当前局限性。最近的报道表明，某些Zwitterionic和两氧化液聚合物可有效抑制生物污染。但是，缺乏对这种行为的机械理解。我们假设控制一个小于蛋白质尺寸的一定长度尺寸内的相对电荷基团的空间分离，同时将零净电荷保持在聚合物刷中，从而赋予刷子表面，以抗蛋白质的吸附性。因此，该项目旨在设计和合成零净电荷聚合物刷，并在相对电荷的组之间进行一系列分离，评估它们对蛋白质吸附和细胞粘附的耐药性，并分析相关的结构功能关系。通过肽类聚合物的固相合成，将对电荷分离进行系统研究。该技术允许对单体序列，刷子长度以及电荷分离的绝对控制。研究培训将由研究人员研究小组的多学科概况提供帮助，该小组由医学生和细胞，化学和材料工程的科学家组成。这项研究的结果将包括鉴定适用于治疗和诊断设备的新型抗死刷刷表面，以及对将抗死性质赋予（Pseudo）Zwitterionic材料的构型要求的基本知识。具有分子水平，序列特异性化学和空间提示的聚合物系统的研究将推动引起理想的生物识别特性的生物材料的发展。 公共卫生相关性：这项实验研究将系统地研究赋予具有均衡静电电荷的聚合物赋予抗死特性所需的分子结构。使用这种抗死聚合物的生物医学设备涂覆生物医学设备将防止生物分子和细胞不必要的污染，从而改善设备的性能和患者的结果，并降低医疗费用。