All-Polysaccharide, Self-Healing Injectable Hydrogels Based on Chitosan and Oxidized Hydroxypropyl Polysaccharides

Polysaccharide-based hydrogels are attractive materials for biomedical applications for reasons that include their polyfunctionality, generally benign nature, and biodegradability. However, the use of polysaccharide-based hydrogels may be limited by toxicity arising from small-molecule crosslinkers, or may involve undesired chemical modification [Hennink, W. E.; et al. Adv. Drug Delivery Rev. 2012, 64, 223-236]. Here, we report a green, simple, efficient strategy for the preparation of polysaccharide-based, in situ forming hydrogels. The Edgar group reports in the accompanying manuscript that chemoselective oxidation of oligo(hydroxypropyl)-substituted polysaccharides introduces ketone groups at the termini of the side chains [Nichols, B. L. B.; et al]. Amine-containing moieties can condense with ketones to form imines. The imine linkage is dynamic in the presence of water, providing the potential for self-healing [Wei, Z.; et al. Adv. Fund. Mater. 2015, 25, 1352-1359], injectability [Wei, Z.; et al. Adv. Funct. Mater. 2015, 25, 1352-1359], and pH responsiveness [Yao, K.; et al. J. Appl. Polym. Sci. 1993, 48, 343-354]. In this work, we designed and prepared two different types of hydrogels, oxidized hydroxypropyl cellulose/chitosan (Ox-HPC-Chitosan) and oxidized hydroxypropyl dextran/chitosan (Ox-HPD-Chitosan), each cross-linked by imine bonds. The mechanical properties of these hydrogels were characterized by rheometry, revealing that hydrogel storage modulus could be tuned from 300 Pa to 13 kPa simply by controlling the degree of substitution (DS) of ketone groups. Rheological characterization also illustrated the rapid self-healing property of these all-polysaccharide hydrogels. Moreover, these hydrogels exhibited high swelling rates and facile injectability. Therefore, this work reveals a potential strategy for the construction of hydrogels that require no small-molecule crosslinkers and are therefore highly attractive for biomedical, agricultural, controlled release, and other applications.