Active Hyaluronan Polymer Brushes for Tunable Biointerfaces

点击翻译按钮获取中文摘要

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.