Highly tunable chitosan and carboxymethylated dextran hydrogels crosslinked with NHS/EDC with potential application for preventing postoperative adhesions

Abstract

Postoperative adhesions (POA) are a complication arising after surgery, causing pain and inflammation. Their treatment leads to significant costs, a considerable financial strain on both patients and healthcare systems. To address this issue, we have developed fully biocompatible hydrogels composed of chitosan (CHI) and carboxymethylated dextran (CMD), chemically crosslinked with carbodiimide chemistry (i.e. NHS/EDC) and producing no undesired side-reactions, as a potential surgical aid and physical barrier against POA. Of interest, CHI is used without any chemical modification, since the addition of sodium bicarbonate to the formulation promotes both its solubilisation at nearly neutral or slightly alkaline pH, and inhibits CHI uncontrolled complexation and precipitation with CMD, yielding uniform and transparent hydrogels. We tested a wide range of CHI:CMD mixtures for their gelling kinetics. Those were shown to be tuned with temperature, ranging from approx. 1 min at 37 °C, to over 30 min at 4 °C - making these hydrogels injectable and/or moldable. Ultimately, we showed that the crosslinking chemistry using NHS/EDC can be used with pristine CHI and any biopolymer containing carboxylic groups, making this approach accessible, well-defined and highly versatile for the preparation of hydrogels destined to the prevention of POA, and for biomedical applications in general.