IO4- -stimulated crosslinking of catechol-conjugated hydroxyethyl chitosan as a tissue adhesive

Abstract

Catechol-functionalized polymers are of particular interest because of their strong water-resistant adhesive properties. Hydroxymethyl chitosan (HECTS) has been used as an implantable biomaterial having good water solubility, biodegradability and biocompatibility. Here, hydrocaffeic acid (HCA) grafted HECTS (HCA-g-HECTS) was prepared through carbodiimide coupling and the tethered catechol underwent periodate ( ${\text{IO}}_4^{-}$ )-stimulated mono and double cross-linking with genipin. The gelation time of these cross-linked HCA-g-HECTS hydrogels decreased with increasing molar ratio of cross-linker to grafted catechol group, increasing temperature, or the addition of genipin. Under the same molar ratio of cross-linker to catechol, ${\text{IO}}_4^{-}$ -induced cross-linked HCA-g-HECTS hydrogels exhibited much stronger storage modulus and temperature stability than hydrogels made by Fe³⁺ -triggered cross-linking. The ${\text{IO}}_4^{-}$ -stimulated HCA-g-HECTS hydrogels were biocompatible on a cellular level when the molar ratio of ${\text{IO}}_4^{-}$ to catechol group was less than 0.5:1. The hydrogels prepared with a 0.125:1 molar ratio of ${\text{IO}}_4^{-}$ to catechol group exhibited high adhesion strength of 73.56 kPa against wet rat skin, and a higher adhesion strength than sutures in a rat wound closure model. This biocompatible ${\text{IO}}_4^{-}$ -stimulated HCA-g-HECTS hydrogel may represent a promising new tissue adhesive. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 582-593, 2019.

Keywords: catechol group; hydrogel; hydroxyethyl chitosan; tissue adhesive.