Zero Net Charge Polymer Brush Surfaces Highly Resistant to Protein Adsorption

描述（由申请人提供）：创造耐用、功能性和生物相容性的植入物和传感器是改善患者预后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装置的表面污染，以及随之而来的表面诱导的血栓和炎症反应，降低了装置的性能，并导致需要医疗干预的不良后果。针对防止生物污染的表面修饰的广泛文献强调了该策略在改善医疗设备和健康结果方面的广泛潜力和当前局限性。最近的报道表明，某些两性聚合物和两性聚合物在抑制生物污染方面是有效的。然而，缺乏对这种行为的机械理解。我们假设，在小于蛋白质大小的一定长度尺度内控制极性基团的空间分离，同时保持聚合物刷的零净电荷，使刷表面具有蛋白质吸附的阻力。因此，本项目旨在设计和合成具有一定距离的零净电荷聚合物刷，评估其对蛋白质吸附和细胞粘附的抵抗力，并分析相关的结构-功能关系。模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。这种技术允许对单体序列、电刷长度和电荷分离进行绝对控制。这项研究培训将得到研究者研究小组的多学科概况的帮助，该小组由医学学生和细胞、化学和材料工程方面的科学家组成。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。对具有分子水平、序列特异性化学和空间线索的聚合物系统的研究将促进生物材料的发展，从而获得理想的生物识别特性。

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.