Collaborative Research: Conformal Assemblies of Polyphosphazenes with Controlled Biofunctionality

第一部分：非技术概述本项目专注于工程多功能生物材料，具有先进的功能，如可控的蛋白质吸附和自我修复能力。许多目前的临床聚合物涂层一旦进入人体，就会容易在表面积聚蛋白质。虽然已经提出了解决方案，但将排斥蛋白质的能力与其他先进能力结合起来，如自我修复和可控药物释放，仍然是一个挑战。该项目专注于为冠状动脉支架、导管或人工植入物等设备创造涂层，这些设备都与各种生物环境密切接触。因此，希望这种涂层(A)易于以可控的方式应用于各种生物医学相关的基质；以及(B)与可预测的、无毒的降解成分具有生物相容性和生物降解性。逐层(LBL)技术被选为一种强有力的手段，可以在所有水性组件的几乎任何表面上创建厚度可控的保形涂层。该项目将探索新型杂化聚合物的能力，这些聚合物以具有结构多样性的有机侧基的无机骨架为基础，通过LBL技术进行组装，经历受控降解，并促进生物活性分子的调制释放。其目标将是实现易于制造的生物兼容涂层，并结合所需的性能。先进的仪器技术将用于了解涂层化学对自我修复能力、防止蛋白质粘连、加载/释放药物以及控制与生物环境相互作用的能力的影响。重要的是，这个项目将为参与的研究生和本科生创造一个肥沃的培训场地，这些学生将通过农业研究计划招募。One PI目前是“材料科学中的女性”(WIMS)组织的学术顾问，该组织通过积极参与校内外的外联活动，促进女性和少数族裔学生进入科学与工程专业。另一位PI则积极参与中学生“科学与医学前沿日”活动。第二部分：技术总结寻找连接生物系统的多功能生物材料，如人工植入物，包括冠状动脉支架和导管，是生命科学中最关键和最具挑战性的领域之一。目前临床上使用的聚合物涂层是以传统的商品聚合物为基础的，通常是使用有机溶剂通过溶液浇注在固体表面沉积，缺乏所需的化学功能，并且对生物活性物质的加载和释放进行可靠的控制。这项建议旨在(A)探索基于具有定制生物功能的新型聚磷腈(PPz)聚电解质的逐层(LBL)组装的基本性质，(B)通过一系列针对膜的物理化学性质的实验来探索结构-性质关系，并将其与平滑肌和上皮细胞的蛋白质吸附和黏附相关联，以及(C)探索自我修复和受控药物释放的组合。该项目将涉及合成新型PPz聚电解质，它结合了独特的混合性能(极端的链灵活性、前所未有的结构多样性、多功能和受控的水解性)。静电相互作用将被用来形成定义良好的聚电解质多层膜，其厚度和生长模式将用椭偏仪来表征。生物活性分子的包结作用将通过PPzs与带电小分子的直接自组装进行研究，而小分子的载药量和释放量将通过LC-MS进行研究。此外，还将评估这种涂层与人内皮细胞和平滑肌细胞的相互作用、对蛋白质的吸附(HSA、纤维蛋白原)和生物相容性。这些发现将使合理设计用于冠状动脉支架、导管或人工植入物等应用的自我修复和药物加载的生物兼容涂层。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

PART I: NON-TECHNICAL SUMMARY This project focuses on engineering multifunctional biomaterials with advanced capabilities such as controlled protein adsorption and the ability to self-heal. Many current, clinical polymer coatings are susceptible to a build-up of proteins on the surface once in the body. While solutions have been proposed, it remains a challenge to combine the ability to repel proteins with other advanced capabilities such as self-healing and controllable drug release. This project focuses on the creation of coatings for devices such as coronary stents, catheters, or artificial implants, which are all in intimate contact with a large variety of biological milieu. Therefore, it is desirable for such coatings to (a) be easy to apply to a variety of biomedically relevant substrates in a controllable manner; and (b) be biocompatible and biodegradable with predictable, non-toxic degradation components. The layer-by-layer (LbL) technique is chosen as a powerful means to create conformal coatings of controlled thickness on virtually any surface from all aqueous assembly. This project will explore the ability of novel hybrid polymers, which are based on an inorganic backbone with structurally diverse organic pendant groups, to assemble via the LbL technique, undergo controlled degradation, and facilitate modulated release of bioactive molecules. The goal will be to achieve easy to manufacture biocompatible coatings that combine the desired properties. Advanced instrumental techniques will be used to understand the effects of coating chemistry on ability to self-heal, prevent protein adhesion, and load/release drugs along with the ability to control interactions with biological surroundings. Importantly, this project will create a fertile training ground for the participating graduate and undergraduate students which will be recruited via the Aggie Research Program. One PI is currently the academic advisor of the "Women in Materials Science" (WIMS) organization, which promotes the inclusion of female and minority students in science & engineering through active engagement in outreach activities both on and off campus. The other PI is actively involved in "Frontiers in Science and Medicine Day" for middle school students. PART II: TECHNICAL SUMMARYThe search for multifunctional biomaterials interfacing biological systems, such as artificial implants, including coronary stents and catheters, is one of the most critical and challenging areas of life sciences. Current polymer coatings in clinical use are based on traditional commodity polymers, are often deposited on solid surfaces via solution casting using organic solvents, lack desired chemical functionalities, and reliable control over loading and release of bioactives. This proposal aims to (a) explore the fundamental properties of layer-by-layer (LbL) assemblies based on novel polyphosphazene (PPz) polyelectrolytes with tailored bio-functionality, (b) probe structure-property relationships through a set of experiments addressing physico-chemical properties of the films, and relate them to protein adsorption and adhesion of smooth muscle and epithelial cells, and (c) explore the combination of self-healing and controlled drug release. This project will involve synthesizing novel PPz polyelectrolytes, which combine a unique mixture of properties (extreme chain flexibility, unprecedented structural diversity, multi-functionality, and controlled hydrolytic degradability). Electrostatic interactions will be used to form well defined polyelectrolyte multilayers, whose thickness and growth patterns will be characterized with ellipsometry. Inclusion of bioactive molecules will be studied through direct self-assembly of PPzs with small charged molecules, while amount loaded and released of small molecules will be studied using LC-MS. Moreover, the interaction of such coatings with human endothelial and smooth muscle cells, adsorption of proteins, (HSA, fibrinogen) and biocompatibility will be assessed. These findings will enable rational design of biocompatible coatings for self-healing and drug-loading for applications such as coronary stents, catheters, or artificial implants.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.