Coacervation and adhesion mechanism of PEI/TA hydrogel revealed by molecular dynamics simulations.

Abstract

Coacervate-derived polyethyleneimine (PEI)/thioctic acid (TA) hydrogels can efficiently repel interfacial water and achieve robust underwater adhesion on diverse substrates, thus representing a promising material for a wide range of biomedical uses such as wound dressings, hemostatic agents, drug carriers, and tissue repair. Understanding the cohesion and adhesion dynamics in this coacervate-to-hydrogel strategy is critical for the development of underwater bioadhesive. However, these mechanisms remain obscure due to the difficulty of obtaining the atomic details. In this work, we first applied quantum calculations and classical mechanics models to obtain accurate force field parameters for PEI and TA. Based on the refined force field, we employed microsecond-long all-atom molecular dynamics (MD) simulations to investigate the coacervation of PEI/TA complex and its adhesion on glass and polypropylene. Our simulations revealed that the phase transition in PEI/TA coacervation was jointly achieved by two types of aggregation, i.e., TA-TA aggregation through hydrophobic associations and PEI-TA aggregation driven by electrostatic interactions. In addition, MD simulations further depicted the distinct adhesion modes of PEI/TA on the two substrates. TA assembled on top of the hydrophobic polypropylene substrate, replacing the interfacial water, whereas PEI amines penetrated the interfacial water to directly bind to the silanols of the hydrophilic glass substrate. The tight adhesion of PEI/TA hydrogel was then quantified by the diffusion coefficient of molecular moieties, which reflected the extremely low mobility of the bound moieties. These findings deepen our understanding of the formation and adhesion of PEI/TA hydrogel at the atomic level and provide guidance for the future design of advanced bioadhesive for potential clinical applications.