Effect of poly(ethylene glycol)-based cross-linker length on the physicochemical and rheological properties of hyaluronic acid hydrogels potentially applicable in the biomedical field

The development of safe and effective hyaluronic acid-based materials is one of the main research focuses for biomedical applications. However, so far, an investigation of the influence of the cross-linker chain length on the physicochemical, mechanical, and rheological properties of the material has never been reported. Therefore, in the present work, a polydisperse poly(ethylene glycol) diglycidyl ether (PEGDE) and six monodisperse PEGDE with a well-defined length were successfully synthesized by a simple method and used as cross-linkers of hyaluronic acid to obtain hydrogels which differed only for the length of the cross-linker. Our results indicate that the cross-linking density, determined by using Flory-Rehner equation, and the total content of the cross-linker in the formulation, determined by 1 H NMR, decrease with PEGDE length. However, the formulations with the longer polydisperse PEGDEs (n ≥ 6) exhibits a higher storage modulus ( G ' = 110.4-114.7 Pa) and a stiffer mechanical behaviour, indicating that cross-linker chain length influences significantly the rheological properties of hydrogels.