Rheological Characterization of Genipin-Based Crosslinking Pigment and O-Carboxymethyl Chitosan–Oxidized Hyaluronic Acid In Situ Formulable Hydrogels

Abstract

The aim of this study was to develop a material capable of rapidly absorbing bodily fluids and forming a resilient, adhesive, viscoelastic hydrogel in situ to prevent post-surgical adhesions. This material was formulated using O-carboxymethyl chitosan (O-CMCS), oxidized hyaluronic acid (OHA), and a crosslinking pigment derived from genipin and glutamic acid (G/GluP). Both crosslinked (O-CMCS/OHA-G/GluP) and non-crosslinked hydrogels (O-CMCS/OHA) were evaluated using a HAAKE™ MARS™ rheometer for their potential as post-surgical barriers. A rheological analysis, including dynamic oscillatory measurements, revealed that the crosslinked hydrogels exhibited significantly higher elastic moduli (G′), indicating superior gel formation and mechanical stability compared to non-crosslinked hydrogels. The G/GluP crosslinker enhanced gel stability by increasing the separation between G′ and G″ and achieving a lower loss tangent (tan δ < 1.0), indicating robustness under dynamic physiological conditions. The rapid hydration and gelation properties of the hydrogels underscore their effectiveness as physical barriers. Furthermore, the O-CMCS/OHA-G/GluP hydrogel demonstrated rapid self-healing and efficient application via spraying or spreading, with tissue adherence and viscoelasticity to facilitate movement between tissues and organs, effectively preventing adhesions. Additionally, the hydrogel proved to be both cost effective and scalable, highlighting its potential for clinical applications aimed at preventing post-surgical adhesions.