Tailoring thermoreversible hyaluronan hydrogels by "click" chemistry and RAFT polymerization for cell and drug therapy.

Thermoreversible hydrogels are promising matrices for tissue-engineered cartilage and spine constructs. They require specific properties during all the stages of a cell therapy (e.g., cell expansion, recovery, injection, delivery). Thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HA-PNIPAM) hydrogels with well-defined molecular architecture and properties were synthesized through RAFT polymerization and "click" chemistry. The effect of PNIPAM grafting length and density on HA-PNIPAM properties was evaluated by methods relevant for a cell therapy. It was found that reversibility of the PNIPAM gelling process was improved in the presence of HA. Increasing M(n) of PNIPAM decreased the viscosity at 20 degrees C and led to high G' at T > 30 degrees C; however, higher grafting density led to lower mechanical properties. Water uptake of the hydrogels was mainly dependent on PNIPAM M(n). All of the hydrogels and their degradation products were cytocompatible to hTERT-BJ1 fibroblasts. A composition with properties ideal for cell encapsulation was identified and characterized by a low viscosity at 20 degrees C, rapid gelling at 37 degrees C, absence of volume change upon gelling, and G' of 140 Pa at 37 degrees C.