(165u) Combinatorial Approach to Assess Self-Assembly Dynamics and Structure Properties of Alkyl Chain Modification of Hyaluronic Acid Hydrogels

Hydrogels have been identified as biomaterials of significant interest owing to their unique properties—hydrophilic structures, high degree of structural flexibility, low toxicity, biocompatibility—that qualify them as ideal candidates in a widening range of biomedical and pharmaceutical applications from wound dressing surface coatings, to drug delivery composites, and tissue scaffolds. However, the desired properties of hydrogels simultaneously endow such materials with inherent shortcomings that have hindered their prolific implementation; specifically, hydrogels suffer from low mechanical stability and loss of native function upon exposure to industrial solvents. One proposed technique to overcome these challenges and thus functionalize hydrogels for a wider range of biomedical applications is the chemical modification of such materials to elicit controllable changes in hydrogel structure and function to thus fulfill user-defined/user-designed applications. While the chemical modification of hydrogels has led to the successful design and employment of biopolymers with more varied mechanical and biological properties, the strategy further drives the need for an in-depth understanding of the physical and chemical phenomena that drive the assembly of modified biopolymers and thus determine biopolymer functionality for a given application.

We hypothesize that a combinatorial approach based on both molecular dynamics (MD) simulations and analytical techniques could be used to probe the self-assembly of alkyl chain-modified hyaluronic acid (HYA)—a model polymer chosen for its hydrophilicity, relative abundance, biocompatibility, and periodic carboxylate reactive group. Such a strategy will allow for control of the assembly dynamics of modified HYA such that it can predict end-structure properties of alkyl-chain modified HYA networks to ultimately define porosity, average pore aperture size, and accessible surface area, all important characteristics to increase such polymer implementation in biomedical industries. Modified HYA chains were synthesized via 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated amine group attachment of dodecylamine to the periodic carboxylate group on the HYA backbone. Material characterization including Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were conducted to confirm the expected EDC reaction chemistry and to assess the water uptake capacity of the modified hydrogels, respectively, while gas adsorption studies and atomic force microscopy (AFM) were used to analyze structural differences between modified and unmodified HYA. MD simulations of both unmodified and modified HYA chains—varied lengths of attached alkyl groups as well as varied degrees of alkyl group substitution on the HYA backbone—were carried out to analyze the self-assembly dynamics of the chains and determine how differences in chemical modification eventuate critical differences in the end structure properties. Our findings demonstrate that targeted, atomic-level investigation as well as corroborated analytical analyses of the assembly of chemically modified hydrogels are necessary to develop the next generation of fully optimized biomaterials that have extended applicability beyond biomedical and pharmaceutical applications including in biosensing and decontamination.