An injectable hyaluronic acid–tyramine hydrogel system for protein delivery

Previously, we reported the independent tuning of mechanical strength (crosslinking density) and gelation rate of an injectable hydrogel system composed of hyaluronic acid–tyramine (HA–Tyr) conjugates. The hydrogels were formed through the oxidative coupling of tyramines which was catalyzed by hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Herein, we studied the encapsulation and release of model proteins using the HA–Tyr hydrogel. It was shown that the rapid gelation achieved by an optimal concentration of HRP could effectively encapsulate the proteins within the hydrogel network and thus prevented the undesired leakage of proteins into the surrounding tissues after injection. Hydrogels with different mechanical strengths were formed by changing the concentration of H2O2 while maintaining the rapid gelation rate. The mechanical strength of the hydrogel controlled the release rate of proteins: stiff hydrogels released proteins slower compared to weak hydrogels. In phosphate buffer saline, α-amylase (negatively charged) was released sustainably from the hydrogel. Conversely, the release of lysozyme (positively charged) discontinued after the fourth hour due to electrostatic interactions with HA. In the presence of hyaluronidase, lysozymes were released continuously and completely from the hydrogel due to degradation of the hydrogel network. The activities of the released proteins were mostly retained which suggested that the HA–Tyr hydrogel is a suitable injectable and biodegradable system for the delivery of therapeutic proteins.

In vivo fluorescence imaging shows that rapid gelation prevents the diffusion of fluorescent proteins away from the injection site.Figure optionsDownload as PowerPoint slide