Stable and biocompatible hydrogel composites based on collagen and dialdehyde carboxymethyl cellulose in a biphasic solvent system.

Stable hydrogels with a mechanically strong matrix microenvironment are favorable biomaterials for three-dimensional cell culture. Acidic collagen solution is commonly combined with chemical crosslinkers for rapid network formation. Herein, dialdehyde carboxymethyl cellulose (DCMC) was selected as an optimal crosslinking reagent for its excellent biocompatibility and suitable chemical reactivity. Both shielding of electrostatic attractions between these two oppositely charged biomaterials and obtaining concentrated collagen solution were achieved using a novel biphasic acetic acid /1-ethyl-3-methylimidazolim acetate (AA/[EMIM][Ac]) solvent system. Hydrogel composites containing more crosslinks were obtained by increasing collagen concentrations (5-25 mg/mL), as confirmed by the improved mechanical properties, thermal denaturation temperature, anti-enzymatic ability and compact microstructure. Moreover, cell proliferation assay demonstrated that all the obtained DCMC-crosslinked collagen hydrogel composites ensures commendable biocompatibility. This study provides a promising strategy for manipulating stable and biocompatible hydrogel composites by blending concentrated collagen solution with DCMC in a biphasic solvent system.