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：格鲁吉亚理工学院材料研究部生物材料项目的这一奖项是为了合成和表征一种称为透明质酸的特定类型的糖基聚合物，该聚合物具有可调、可编程和动态的功能特性。这些刷状聚合物广泛分布，并作为细胞和周围基质（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的方向性、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是罕见的，其中一些特性的复制还有待于通过合成手段来实现。受细胞实现的精致界面控制的启发，该奖项将使用细胞表面称为透明质酸合成的生物催化剂合成透明质酸的大分子。这些动态的和可再生的界面预计将产生生物催化剂的密集阵列，这反过来又会在表面上产生透明质酸。这些界面材料是独特的，原因有很多：它们可以再生;它们的厚度可从100 nm到20微米调节，使它们成为有史以来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;并且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，药物递送，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的培训，并将使小学生接触到科学和工程新材料的创造性方面，受到生物学的启发。技术摘要：接口在许多生物医学应用中至关重要，从生物传感到蛋白质纯化，到抗菌涂层，到组织修复和再生，再到生物工程。特别是，聚合物刷是一个有吸引力的策略，用于设计功能表面，因为它们将允许控制的一些重要的结构特征，允许调整的界面特性。研究者已经建立了一种策略，使用移植方法生产可调的、自愈合的极厚透明质酸（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，该生物催化剂透明质酸合酶合成HA并将HA挤出穿过尺寸大至20微米的细胞膜。 活性HA合成酶刷接口是具有许多潜在应用的迷人系统。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的响应，如溶剂质量，pH值和离子强度。此外，该奖项将调查刷的动力学方面，并将解决有关其再生能力的重要问题，包括：1）如何刷年龄一旦酶合成停止？2)如果酶的合成永不停止，一把刷子能维持多久？（3）一把刷子在拔下后可以再生多少次？以及4）在受限几何形状中的酶界面的功能是什么，如在插入组织中的装置上实现的那些（以及在体内的细胞-细胞和细胞-细胞外基质界面处发现的那些）。更好地了解HA合酶的酶功能和HA刷形成的限制是相关的生物材料的应用，以及更广泛地了解HA丰富的糖萼整合和协调细胞的粘附和相互作用，以他们的环境。该奖项的科学影响广泛，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。该奖项由物理和数学科学理事会材料研究部的生物材料计划和BioMaPS基金以及化学、生物工程、生物医学和生物工程部的催化计划共同支持。环境和运输系统在工程局。

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.