Hyperbranched phosphoramidate-hyaluronan hybrid: A reduction-sensitive injectable hydrogel for controlled protein release

In the study, an injectable hybrid hydrogel (HPPAE-HA) was fabricated by in situ polymerization between acrylated hyperbranched polyphosphoramidate (HPPAE-AC) and thiolated hyaluronan (HA-SH) via Michael-addition reaction. Gelation times ranged from 4 to 360 min, depending on the stoichiometric ratio of HA-SH to HPPAE-AC, HA concentration and solution pH. In addition, due to the readily oxidation of thiol groups, the HPPAE-HA hydrogel bears disulfide bond. The DTT triggered disulfide bond cleavage and the subsequent cross-linking between thiol and abundant acryloyl groups presented in HPPAE-HA hydrogel contribute to the controlled release of bovine serum albumin (BSA) from the hydrogels. The burst release of BSA from HPPAE-HA hydrogel decreased from 23.7 to 4.0% during the first 3 h, and the 80% cumulative release of BSA was retarded for 12 h to nearly 96 h in 10 mM DTT. The facile synthesis of Michael-additional, disulfide containing HPPAE-HA hydrogel may enable further development of hydrogel matrices potentially suitable for tissue engineering and drug delivery applications.