Active Hyaluronan Polymer Brushes for Tunable Biointerfaces

摘要：该奖项由乔治亚理工学院材料研究部生物材料项目颁发，旨在表彰一种特殊类型的糖基聚合物透明质酸的合成和表征，这种聚合物具有可调、可编程和动态的功能特性。这些刷状聚合物分布广泛，是细胞与周围基质（细胞外基质）之间的生物界面。透明质酸之间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没有通过合成手段来实现。受细胞实现的精细界面控制的启发，该奖项将在细胞表面使用称为透明质酸合成的生物催化剂合成大的透明质酸大分子。这些动态和可再生的界面有望产生密集的生物催化剂阵列，从而在表面上产生透明质酸。这些界面材料是独一无二的，原因有很多：它们可以再生；它们的厚度从100纳米到20微米不等，这使它们成为有史以来报道过的最厚的聚合物刷子之一。由于这些原因，合成的聚合物被认为是一种完全不同的HA材料；它们由一种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方面。技术摘要：界面在生物传感、蛋白质纯化、抗菌涂层、组织修复和再生以及生物工程等许多生物医学应用中都是至关重要的。特别是，聚合物刷是设计功能性表面的一种有吸引力的策略，因为它们允许控制许多重要的结构特征，从而允许调整界面特性。研究人员已经建立了一种策略，可以使用接枝方法生产可调的、自修复的极厚透明质酸（HA）聚合物刷。这是通过密集排列的生物催化剂透明质酸合成酶（HA合成酶）来实现的，该酶可以合成并通过大小为20微米的细胞膜挤压HA。活性HA合成酶刷界面是一个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)如果酶的合成从未停止，刷能保持多长时间？3)梳子拔掉后能再生几次？4)在受限的几何结构中，酶界面的功能是什么，比如在插入组织的设备上实现的功能（以及在体内细胞-细胞和细胞-细胞外基质界面上发现的功能）。更好地了解透明质酸合成酶的功能和封闭条件下透明质酸刷的形成，不仅关系到生物材料的应用，也关系到更广泛地了解富含透明质酸的糖萼在整合和协调细胞与周围环境的粘附和相互作用方面的作用。该奖项对科学的广泛影响体现在不同的生物材料应用领域，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局材料研究部的生物材料计划和生物材料计划基金，以及工程局化学、生物工程、环境和运输系统部的催化计划共同支持。

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.