Collaborative Research: Conformal Assemblies of Polyphosphazenes with Controlled Biofuncationality

合作研究：具有受控生物功能的聚磷腈的共形组装

• 批准号: 1808531
• 负责人: Alexander Andrianov
• 金额: $ 22万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808531&HistoricalAwards=false
• 关键词: Collaborative; Research; Conformal; Assemblies; Polyphosphazenes

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.

第一部分：非技术概述该项目的重点是工程多功能生物材料与先进的能力，如控制蛋白质吸附和自我修复的能力。许多当前的临床聚合物涂层一旦进入体内就容易在表面上积聚蛋白质。虽然已经提出了解决方案，但将联合收割机排斥蛋白质的能力与其他先进的能力（例如自修复和可控的药物释放）相结合仍然是一个挑战。该项目的重点是为冠状动脉支架、导管或人工植入物等设备创建涂层，这些设备都与各种各样的生物环境密切接触。因此，期望这样的涂层（a）易于以可控的方式施加到各种生物医学相关的基底上;和（B）具有生物相容性和生物可降解性，具有可预测的无毒降解组分。选择逐层（LbL）技术作为在几乎所有水性组件的任何表面上创建受控厚度的保形涂层的有力手段。该项目将探索新型混合聚合物的能力，该聚合物基于具有结构多样的有机侧基的无机主链，通过LbL技术组装，进行受控降解，并促进生物活性分子的调节释放。目标将是实现易于制造的生物相容性涂层，联合收割机所需的属性。先进的仪器技术将用于了解涂层化学对自我修复能力的影响，防止蛋白质粘附，并加载/释放药物沿着控制与生物环境相互作用的能力。重要的是，该项目将为参与研究生和本科生创造一个肥沃的培训基地，这些学生将通过农业研究计划招募。一名PI目前是“材料科学中的女性”组织的学术顾问，该组织通过积极参与校内和校外的外联活动，促进女性和少数民族学生参与科学工程。另一名PI积极参与中学生的“科学和医学前沿日”。第二部分：技术概述寻找与生物系统连接的多功能生物材料，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。目前临床使用的聚合物涂层基于传统的商品聚合物，通常通过使用有机溶剂的溶液浇铸沉积在固体表面上，缺乏所需的化学功能，以及对生物活性物质的负载和释放的可靠控制。该提案旨在（a）探索基于具有定制生物功能性的新型聚磷腈（PPz）聚电解质的层层（LbL）组装体的基本性质，（B）通过一组针对膜的物理化学性质的实验来探测结构-性质关系，并将它们与平滑肌和上皮细胞的蛋白质吸附和粘附相关联，以及（c）探索自修复与药物控制释放的结合。该项目将涉及合成新型PPz聚电解质，该聚电解质结合了联合收割机独特的混合性能（极高的链柔性，前所未有的结构多样性，多功能性和可控的水解降解性）。静电相互作用将被用来形成良好定义的多层膜，其厚度和生长模式将与椭圆偏振特性。将通过PPZ与小带电分子的直接自组装来研究生物活性分子的包含，同时将使用LC-MS研究小分子的装载和释放量。此外，将评估这种涂层与人内皮细胞和平滑肌细胞的相互作用、蛋白质（HSA、纤维蛋白原）的吸附和生物相容性。这些发现将使合理设计的生物相容性涂层的自我愈合和药物负载的应用，如冠状动脉支架，导管，或artificial implants.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

项目成果

Ionic Fluoropolyphosphazenes as Potential Adhesive Agents for Dental Restoration Applications

离子型氟聚磷腈作为牙齿修复应用的潜在粘合剂

• DOI: 10.1007/s40883-020-00192-w
• 发表时间: 2021
• 期刊: Regenerative Engineering and Translational Medicine
• 影响因子: 2.6
• 作者: Weir, Michael D.;Kaner, Papatya;Marin, Alexander;Andrianov, Alexander K.
• 通讯作者: Andrianov, Alexander K.

Next generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine.

• DOI: 10.1016/j.nano.2021.102359
• 发表时间: 2021-04
• 期刊: Nanomedicine : nanotechnology, biology, and medicine
• 作者: Marin A;Chowdhury A;Valencia SM;Zacharia A;Kirnbauer R;Roden RBS;Pinto LA;Shoemaker RH;Marshall JD;Andrianov AK
• 通讯作者: Andrianov AK

Protein-loaded soluble and nanoparticulate formulations of ionic polyphosphazenes and their interactions on molecular and cellular levels

• DOI: 10.1016/j.msec.2019.110179
• 发表时间: 2020-01-01
• 期刊: MATERIALS SCIENCE AND ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
• 影响因子: 7.9
• 作者: Andrianov, Alexander K.;Marin, Alexander;Fuerst, Thomas R.
• 通讯作者: Fuerst, Thomas R.