# On the Conditions Determining the Formation of Self-Crosslinking Chitosan Hydrogels with Carboxylic Acids

## TL;DR

This paper investigates how different chemical structures affect the formation and properties of self-crosslinking chitosan hydrogels using carboxylic acids.

## Contribution

The study reveals that the length and flexibility of the spacer group significantly influence the gelation and mechanical properties of chitosan hydrogels.

## Key findings

- Chitosan forms gels with N-carboxyalkyl derivatives, with stiffness increasing with longer alkyl spacers.
- N-succinyl chitosan forms gels across all acylation levels but is less stiff than N-carboxypropyl chitosan.
- A long and flexible spacer is crucial for effective crosslinking and gel formation.

## Abstract

The formation of self-crosslinking chitosan hydrogels using carboxylic acids has a number of limitations. Chitosan dissolves in oxalic, malonic, and succinic acids at a ratio of 1 amino group to 2 carboxyl groups into viscous solutions (G′ < G′′), but does not dissolve with lower amounts of the acid. Mixing chitosan hydrochloride with disodium carboxylates does not afford gels, but only a coacervate in the case of disodium oxalate, which dissolves upon dialysis. In the homologous series of N-carboxyalkyl derivatives (alkyl = methyl, ethyl, propyl), all members form gels (G′ > G′′). At approx. 50% of substitution, the storage modulus increases from 40 Pa (methyl) to 30,000 Pa (propyl) indicating the increasing strength of intermolecular interactions with the increasing length of the alkyl spacer. This could indicate that a sufficiently long spacer is required to properly connect the chitosan helices. N-succinyl chitosan, where the spacer is attached to the backbone as an amide, also forms polymer gels across all degrees of N-acylation. When compared to N-carboxypropyl chitosan, the latter forms significantly stiffer gels that swell less. This indicates that one covalent bond, a sufficient length, and the conformational flexibility of the spacer are important for gelation.