Active Hyaluronan Polymer Brushes for Tunable Biointerfaces

用于可调生物界面的活性透明质酸聚合物刷

• 批准号: 1709897
• 负责人: Jennifer Curtis
• 金额: $ 36万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1709897&HistoricalAwards=false
• 关键词: Active; Hyaluronan; Polymer; Brushes; Tunable

Non-Technical Abstract:This award by the Biomaterials Program in the Division of Materials Research to Georgia Institute of Technology is for the synthesis and characterization of a specific type of sugar-based polymers called hyaluronans, which would have tunable, programmable and dynamic functional properties. These brush polymers are widely distributed, and function as biointerfaces between cells and surrounding matrix called extra cellular matrix. The interactions of hyaluronans are highly directional, specific, and reversible, and these interactions are the foundation of all living systems. Biomaterials that are both programmable and regenerative are rare, and reproduction of some of these properties are yet to be made by synthetic means. Inspired by the exquisite interface control realized by cells, this award would synthesize large macromolecules of hyaluronan using biocatalysts called hyaluronan synthese on the cell surface. These dynamic and regrowable interfaces are expected in generating dense arrays of the biocatalysts, which in turn will produce hyaluronan on surfaces. These interfacial materials are unique for a number of reasons: they can regenerate; and they are tunable in thickness from 100 nm to 20 microns, making them as one of the thickest polymer brushes ever reported. For these reasons, the polymers synthesized are considered a completely distinct class of HA material; and are comprised of a ubiquitous biopolymer with properties that make it particularly attractive for different biomaterials applications and interfaces including tissue repair, healing and regeneration, drug delivery, immunotherapy among others. As part of this project, interdisciplinary training will be provided to undergraduate and graduate students, and will expose elementary school students to the creative aspect of science and engineering new materials, as inspired by biology.Technical Abstract:Interfaces are crucial in many biomedical applications from biosensing to protein purification to antibacterial coatings to tissue repair and regeneration to bioengineering. In particular, polymer brushes are an attractive strategy for designing functional surfaces, as they would allow the control of a number of important architectural features that allows tuning of interfacial properties. The investigator had already established a strategy to produce tunable, self-healing extremely thick hyaluronan (HA) polymer brushes using a grafting approach. This is achieved using dense arrays of the biocatalyst hyaluronan synthase (HA synthase), which synthesizes and extrudes HA through the cells' membranes with sizes as large as 20 microns. Active HA synthase brush interfaces are a fascinating system with many potential applications. This award will fully characterize the structural properties of these brushes and their response to changes in environmental parameters such as solvent quality, pH, and ionic strength. Further, this award will investigate the dynamical aspect of the brush, and will address important questions about its regenerative capacity including: 1) how does the brush age once the enzyme synthesis is stopped?; 2) if enzyme synthesis is never halted, how long can a brush be maintained?; and 3) how many times can a brush be regrown after its removal?; and 4) what are the functions of the enzyme interfaces in confined geometries, like those realized on devices inserted into tissues (as well as those found at cell-cell and cell-extra cellular matrix interfaces in the body). A better understanding of HA synthase enzyme function and HA brush formation in confinement are relevant to both biomaterials applications as well as a broader understanding of HA-rich glycocalyx in integrating and orchestrating adhesion and interactions of cells to their surroundings. The scientific broader impacts of this award are in different biomaterial applications including tissue repair and healing, drug delivery, immunotherapy, biosensing, protein purification, antibacterial coatings and others.This award is jointly supported by the Biomaterials Program and BioMaPS funds of the Division of Materials Research in the Directorate for Physical and Mathematical Sciences, and the Catalysis Program of the Division of Chemical, Bioengineering, Environmental, and Transport Systems in the Directorate for Engineering.

非技术摘要：该奖项由佐治亚理工学院材料研究部生物材料项目颁发，旨在奖励一种称为透明质酸的特定类型糖基聚合物的合成和表征，该聚合物具有可调节、可编程和动态的功能特性。这些刷状聚合物分布广泛，充当细胞和周围基质（称为细胞外基质）之间的生物界面。透明质酸的相互作用具有高度定向性、特异性和可逆性，这些相互作用是所有生命系统的基础。既可编程又可再生的生物材料很少见，并且其中一些特性尚未通过合成方法复制。受细胞实现的精致界面控制的启发，该奖项将使用称为透明质酸合成的生物催化剂在细胞表面合成透明质酸大分子。这些动态且可再生的界面有望产生密集的生物催化剂阵列，进而在表面产生透明质酸。这些界面材料具有独特性，原因有很多：它们可以再生；它们的厚度可在 100 nm 至 20 微米之间调节，使其成为迄今为止报道的最厚的聚合物刷之一。由于这些原因，合成的聚合物被认为是完全不同类别的 HA 材料；由普遍存在的生物聚合物组成，其特性使其对不同的生物材料应用和界面特别有吸引力，包括组织修复、愈合和再生、药物输送、免疫治疗等。作为该项目的一部分，将为本科生和研究生提供跨学科培训，并使小学生受生物学启发，接触到科学和工程新材料的创造性。 技术摘要：接口在许多生物医学应用中至关重要生物传感、蛋白质纯化、抗菌涂层、组织修复和再生、生物工程。特别是，聚合物刷对于设计功能表面来说是一种有吸引力的策略，因为它们可以控制许多重要的结构特征，从而可以调整界面特性。研究人员已经制定了一种策略，使用嫁接方法生产可调节、自修复的极厚透明质酸 (HA) 聚合物刷。这是通过使用生物催化剂透明质酸合酶（HA 合酶）的密集阵列来实现的，该酶合成 HA 并通过尺寸达 20 微米的细胞膜挤出。 活性 HA 合酶刷接口是一个令人着迷的系统，具有许多潜在的应用。该奖项将全面表征这些刷子的结构特性及其对溶剂质量、pH 值和离子强度等环境参数变化的响应。此外，该奖项将研究刷子的动力学方面，并将解决有关其再生能力的重要问题，包括：1）一旦酶合成停止，刷子如何老化？ 2）如果酶的合成永不停止，刷子可以维持多久？； 3) 刷子移除后可以重新生长多少次？ 4）酶界面在有限几何形状中的功能是什么，例如在插入组织的装置上实现的功能（以及在体内细胞与细胞和细胞与细胞外基质界面处发现的功能）。更好地了解HA合酶功能和HA刷在限制中的形成与生物材料应用以及更广泛地了解富含HA的糖萼在整合和协调细胞与其周围环境的粘附和相互作用方面相关。该奖项的科学广泛影响涉及不同的生物材料应用，包括组织修复和愈合、药物输送、免疫治疗、生物传感、蛋白质纯化、抗菌涂层等。该奖项由材料司生物材料计划和BioMaPS基金共同支持物理和数学科学部的研究，以及工程部化学、生物工程、环境和运输系统部的催化项目。

项目成果

Self-regenerating giant hyaluronan polymer brushes

• DOI: 10.1038/s41467-019-13440-7
• 发表时间: 2019-12
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Wenbin Wei;J. Faubel;Hemaa Selvakumar;Daniel T. Kovari;Joanna Tsao;Felipe Rivas;Amar T. Mohabir;Michelle C Krecker;Elaheh Rahbar;A. Hall;M. Filler;Jennifer L. Washburn;P. Weigel;J. Curtis

Sculpting Enzyme-Generated Giant Polymer Brushes

雕刻酶生成的巨型聚合物刷

• DOI: 10.1021/acsnano.0c06882
• 发表时间: 2021
• 期刊: ACS Nano
• 影响因子: 17.1
• 作者: Faubel, Jessica L.;Wei, Wenbin;Curtis, Jennifer E.
• 通讯作者: Curtis, Jennifer E.