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：佐治亚理工学院材料研究部的生物材料计划的奖项是用于合成和表征称为Hyaluronans的特定类型的基于糖的聚合物，该聚合物具有可调，可编程和动态功能性能。这些刷子聚合物被广泛分布，并且在细胞和周围矩阵之间的生物界面作用，称为额外的细胞基质。透明质者的相互作用是高度方向性，特异性和可逆的，这些相互作用是所有生物系统的基础。既可以程序化又是再生的生物材料很少见，并且其中一些特性的繁殖尚未通过合成手段进行。受细胞实现的精美界面控制的启发，该奖项将使用称为透明质酸合成的生物催化剂合成大型透明质酸大分子，称为细胞表面上。这些动态和可再生的接口有望产生生物催化剂的致密阵列，而生物催化剂又会在表面上产生透明质酸。这些界面材料是独一无二的，其原因有很多：它们可以再生；它们的厚度从100 nm到20微米，使其成为有史以来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的HA材料。并由无处不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，药物递送，免疫疗法等。作为该项目的一部分，将向本科生和研究生提供跨学科的培训，并将使小学生接触到受生物学启发的科学和工程新材料的创造性。技术摘要：界面对于许多生物医学应用至关重要，从生物学纯化到蛋白质到蛋白质到抗体涂料到组织涂料和组织修复的蛋白质。特别是，聚合物刷是设计功能表面的有吸引力的策略，因为它们将允许控制许多重要的体系结构特征，以调整界面性能。研究人员已经建立了一种使用接枝方法生产可调，自我修复极为厚的透明质酸（HA）聚合物刷的策略。这是使用生物催化剂透明质酸合酶（HA合酶）的致密阵列来实现的，该酶合成和挤压HA通过细胞的膜，其大小高达20微米。 主动HA合酶刷界面是一个引人入胜的系统，具有许多潜在的应用。该奖项将充分表征这些刷子的结构特性及其对环境参数变化（例如溶剂质量，pH和离子强度）的反应。此外，该奖项将调查刷子的动力学方面，并将解决有关其再生能力的重要问题，包括：1）一旦酶合成的刷子年龄如何停止？ 2）如果酶合成永远不会停止，则可以维持刷子多长时间？ 3）刷子去除后可以再生几次？ 4）酶界面在受约束几何形状中的功能是什么，就像在插入组织中的设备上（以及在人体中细胞细胞和细胞外extra细胞矩阵接口）中所识别的功能。对HA合酶的功能和HA刷形成的更好理解与生物材料的应用有关，以及对富含HA的糖脂的更广泛理解，在整合和编排细胞与周围环境的粘附和相互作用时。 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,和工程局中的运输系统。

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.