Review
Electrical cuing of chitosan's mesoscale organization

https://doi.org/10.1016/j.reactfunctpolym.2020.104492Get rights and content

Abstract

Chitosan is a weak cationic polyelectrolyte that can be cued to undergo reversible pH-dependent self-assembly in which individual chains associate to form macroscopic hydrogels. Nearly 20 years ago it was observed that the high pH cues that induce chitosan's self-assembly can be imposed electrically to induce chitosan hydrogels to electrodeposit on cathode surfaces. These imposed electrical signals (< 5 V) have two components: the current (or rate of electron-transfer from the electrode) that quantifies the localized generation of OH that is responsible for neutralizing chitosan chains and inducing their self-assembly; and the voltage (or field) that can provide a force on the charged chitosan chains to drive their migration toward the cathode and their alignment during electrodeposition. Five years ago, it was reported that an oscillatory ON-OFF electrical input cued the emergence of a segmented hydrogel structure: segments are formed during the ON-step while denser boundary regions are formed during the OFF-step. Later work extended the use of electrical signals to guide the emergence of structure from a dual-responsive chitosan-agarose interpenetrating network. In this short review, we summarize our understanding of the underlying phenomena, and the relevance to the transduction of electrical to structural information and the controllable introduction of hydrogel properties.

Introduction

In 2006, Kjell Varum arranged an introduction between the two corresponding authors and this introduction resulted in a collaboration between the University of Maryland and Wuhan University that has spanned more than a decade and has expanded to other groups both in China and the US. Dr. Shi worked in the Maryland lab between 2007 and 2009; Dr. Payne worked at Wuhan University for 6 months between 2013 and 2016; and two Wuhan University students (Kun Yan and Si Wu) spent a year in the Maryland lab as part of their PhD programs. When this collaboration began, it was already known that chitosan could be electrodeposited through the cathodic neutralization mechanism of Fig. 1a [[1], [2], [3], [4]].

In initial collaborative studies, it was discovered that anodic inputs could be used to activate chitosan for subsequent protein conjugation [5]. The presumptive anodic activation mechanism is illustrated in Fig. 1b. Specifically, anodic oxidation of Cl ions generates reactive species (e.g., HOCl) which can partially oxidize chitosan (e.g., to generate aldehydes) that react with amines to form Schiff base linkages (e.g., to crosslink chitosan chains or to conjugate a protein through its lysine amines). Later work provided support for this proposed mechanism [6] and extended this observation to enable the anodic generation of chitosan with chloramine residues [7].

In 2008, the Domard group in Lyon published their papers on multimembrane hydrogel formation [8,9]. Specifically, this group provided gel-inducing stimuli (base treatments) that caused chitosan's gelation to be repeatedly interrupted resulting in the formation of multilayered structure that has also been referred to as an onion or a segmented structure. The Wuhan group then asked the question: what if the gel-inducing cathodic stimuli were imposed in an oscillatory fashion? Using a cylindrical wire electrode and a cyclic ON-OFF electrical input current (i), they experimentally observed the emergence of a segmented multi-layered structure that could be controllably organized to generate segment regions of various thickness separated by boundary regions (Fig. 1c). These observations stimulated further collaboration, both to understand the fundamental mechanisms associated with chitosan's hierarchical self-assembly, and to create chitosan-based hydrogels with ever-more complex structures, properties and functions [[10], [11], [12], [13]]. Here, we review our current understanding of how electrical inputs can guide the self-assembly of chitosan hydrogels.

Section snippets

Two components of the electrical input signal

To our knowledge, the polysaccharides chitosan [[16], [17], [18]] and alginate [[19], [20], [21]] were the first bio-based polymers to be electrodeposited, while later, independent studies showed that electrical inputs could be used to cue the mesoscale assembly of films/gels from the proteins collagen [[22], [23], [24]] and silk [[25], [26], [27]]. In most cases, the detailed, molecular-level mechanisms of how the electrical input induces individual chains to associate into multi-chain (i.e.,

Electrical to molecular information transduction

A broad focus of our collaborative research is the interconversion of electrical and molecular information. In microelectronics, information is often processed using electrical signals, while biology often uses molecular structure as a means to store, transmit, receive and process information. For instance, a cell-surface receptor may “recognize” and bind an extracellular ligand to induce the protein-protein interactions involved in the intracellular signal transduction that directs the

Conclusions

Chitosan is unique in that is has primary amines in most of its repeating residues and these amines confer important physical-chemical properties. When the amines are protonated chitosan is a water-soluble cationic polyelectrolyte that can form complexes with various anionic species. When the amines are deprotonated, they are nucleophilic and can undergo a chemical reaction with a variety of electrophiles. Also, when their amines are deprotonated the chitosan chains can associate to form

Notes

The authors declare no competing financial interest.

Acknowledgements

This work was supported by the United States National Science Foundation (DMREF-1435957; CBET 1805274) and Defense Threat Reduction Agency (HDTRA11910021), and the National Natural Science Foundation of China (51373124), Fundamental Research Funds for the Central Universities (2042016kf0145) and the China Scholarship Council.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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