Early-stage aggregation of thermo-sensitive chitosan hydrogels: study of the transition from a polymer solution to an attractive colloidal g

Aqueous solutions of chitosan and phosphate salts are highly attractive biomaterials to deliver and encapsulate cell populations, as they are liquid at neutral pH and room temperature and form hydrogels at body temperature. Here, we aim to study the early stages of gelation which have been hitherto little investigated. Preliminary results show that microscopic chitosan-rich aggregates first emerge and form a colloidal suspension that later aggregates to form a colloidal gel. Using time-resolved SAXS and XPCS, we will systematically explore the formation of microscopic structures during gelation as a function of chitosan concentration. We aim to decipher the physical mechanism controlling the formation of these colloidal-like chitosan particles, as well as their attractive interactions. This holds the keys to understanding the microscopic origin of the final microstructural properties of these gels, and will help us defining formulation guidelines to improve cell-hydrogel interactions.