Thermoresponsive dendronized chitosan-based hydrogels as injectable stem cell carriers

Abstract

Stimulus-responsive injectable hydrogels with self-healing properties are promising materials for the delivery of bioactives owing to their protection of the payloads, minimally invasive procedures and site-specific administration. In this work, we report on a type of thermoresponsive dendronized chitosan-based (G1-CS) injectable hydrogel and its potential as scaffolds for stem cell delivery. G1-CS was synthesized through dendronization of chitosan with dendritic oligoethylene glycols (OEGs) to afford characteristic thermoresponsiveness, and its further crosslinking through dynamic covalent Schiff-base chemistry generated the hydrogels. The mechanical properties of the obtained hydrogels are weak with a storage modulus around 0.2 kPa at room temperature, which can be significantly improved to about 1.4 kPa at 37 °C. This feature comes remarkably from thermally induced aggregation and a simultaneously enhanced Schiff-base reaction in an aqueous phase, resulting in promoted crosslinking of the hydrogel network and immediate gelation under physiological conditions. The Schiff-base linkage also endows the hydrogels with shear-thinning and self-healing properties, which facilitate the injection process of the hydrogels and maintenance of their stability. G1-CS hydrogels were examined to encapsulate stem cells. After long term (14 days) culture, the cells exhibited high viability and well maintained their differentiation potential. We therefore believe that hydrogels from this dendronized chitosan, featuring biocompatibility, thermoresponsiveness, self-healing ability, and enhanced mechanical properties, can serve as promising scaffolds for drug delivery and tissue engineering.