Chitosan solubility depends on different factors such as polymer molecular weight, degree of acetylation, pH, temperature, and polymer crystallinity. Homogeneous deacetylation (alkali treatment, 0 °C) of chitin permits the production of polymers soluble in aqueous acetic acid solutions with DD as low as 28%, with this value never being reached under heterogeneous deacetylation (alkali treatment, high temperatures). Moreover, with a DD of 49%, the samples are soluble in water. This behaviour is explained by the fact that homogeneous deacetylation leads to an increase in the number of glucosamine units and a modification in the crystalline structure of the polymer. Depending on polymer DD, these modifications range from a reduction in crystal size and crystal perfection to the presence of a new crystal structure close to β-chitin [18]. Sogias et al. [19] studied the role of crystallinity and inter- or intramolecular forces on chitosan solubility; in this work, a parent chitosan sample was half re-acetylated with anhydride acetic or fully N-deacetylated under homogeneous conditions. After reacetylation, the solubility of the polymer was expanded until pH 7.4, while a slight reduction in the solubility range of the fully deacetylated chitosan was determined. The lower solubility was explained due to the increase in the polymer crystallinity after deacetylation, which offsets the effect of the increase in glucosamine moieties. On the contrary, a reduction in the crystallinity was observed in the half-acetylated sample. The use of hydrogen bond disruptors such as urea or guanidine hydrochloride also alters the solubility window of chitosan. In fact, by a combination of chemical and physical disruption of the hydrogen bonds, broad solubility is achieved.