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

基本信息

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

项目摘要

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：非技术摘要该项目重点关注工程多功能生物材料，其具有先进的功能，例如受控蛋白质吸附和自愈能力。目前许多临床聚合物涂层一旦进入体内，就容易在表面积聚蛋白质。尽管已经提出了解决方案，但将排斥蛋白质的能力与其他先进功能（例如自我修复和可控药物释放）结合起来仍然是一个挑战。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，这些设备都与多种生物环境密切接触。因此，需要这样的涂层：（a）易于以可控的方式施加到各种生物医学相关的基材上； (b) 具有生物相容性和可生物降解性，具有可预测的、无毒的降解成分。逐层 (LbL) 技术被选为一种强大的手段，可以在所有水性组件的几乎任何表面上创建厚度受控的保形涂层。该项目将探索新型杂化聚合物的能力，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。目标是实现易于制造的生物相容性涂层，并结合所需的特性。先进的仪器技术将用于了解涂层化学对自愈能力、防止蛋白质粘附、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，该项目将为通过 Aggie 研究计划招募的研究生和本科生创造一个肥沃的训练基地。一名 PI 目前是“材料科学女性”(WIMS) 组织的学术顾问，该组织通过积极参与校内外的推广活动，促进女性和少数族裔学生融入科学与工程领域。另一位PI积极参与中学生“科学与医学前沿日”活动。第二部分：技术摘要寻找连接生物系统的多功能生物材料，例如人工植入物，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加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的新型聚磷腈（PPz）聚电解质的层层（LbL）组件的基本特性，（b）通过一系列解决物理问题的实验探索结构-性能关系-薄膜的化学性质，并将其与平滑肌和上皮细胞的蛋白质吸附和粘附联系起来，以及（c）探索自愈和受控药物释放的结合。该项目将涉及合成新型 PPz 聚电解质，该电解质结合了独特的性能组合（极端的链灵活性、前所未有的结构多样性、多功能性和受控的水解降解性）。静电相互作用将用于形成明确的聚电解质多层，其厚度和生长模式将通过椭圆光度法进行表征。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 研究小分子的负载和释放量。此外，还将评估此类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）的吸附以及生物相容性。这些发现将有助于合理设计生物相容性涂层，用于冠状动脉支架、导管或人工植入物等应用的自愈和药物装载。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进行评估，被认为值得支持以及更广泛的影响审查标准。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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
影响因子：
0
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

Factors Controlling Degradation of Biologically Relevant Synthetic Polymers in Solution and Solid State