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: 8126946
• 负责人: K. H. Aaron Lau
• 金额: $ 5.13万
• 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/8126946
• 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; 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结局和降低医疗成本的关键。非特异性蛋白质吸附和细胞附着导致的体液接触器械表面污染以及随后的表面诱导血栓形成和炎症反应会降低器械性能，并导致需要医疗干预的不良结局。关于旨在防止生物污染的表面改性的大量文献强调了这种改善医疗器械和健康结果的策略的广泛潜力和当前局限性。最近的报道已经证明，某些两性离子和两性聚合物在抑制生物污垢方面是有效的。然而，缺乏对这种行为的机械理解。我们假设，控制在一定的长度尺度小于蛋白质的大小的带相反电荷的基团的空间分离，同时保持在聚合物刷的零净电荷，赋予刷表面与蛋白质吸附阻力。因此，本项目的目的是设计和合成零净电荷聚合物刷与一系列的分离带相反电荷的基团，评估其抵抗蛋白质吸附和细胞粘附，并分析相关的结构-功能关系。拟肽聚合物的固相合成将使电荷分离的系统研究成为可能。该技术允许绝对控制单体序列、刷长度，从而控制电荷分离。这项研究培训将得到研究者研究小组的多学科简介的帮助，该研究小组由医学生和细胞，化学和材料工程方面的科学家组成。本研究的结果将包括识别适用于治疗和诊断设备的新型防污刷表面，以及赋予（伪）两性离子材料防污性能的配置要求的基本知识。具有分子水平、序列特异性化学和空间线索的聚合物体系的研究将促进生物材料的发展，从而引发期望的生物识别性能。 公共卫生相关性：本实验研究将系统地调查所需的分子结构，赋予防污性能的聚合物拥有平衡的静电电荷数。用这种防污聚合物涂覆生物医学装置将防止生物分子和细胞的不必要的污染，这将改善装置性能和患者结果，并降低医疗成本。