‐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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> )-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, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> -induced cross-linked HCA-g-HECTS hydrogels exhibited much stronger storage modulus and temperature stability than hydrogels made by Fe³⁺ -triggered cross-linking. The <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> -stimulated HCA-g-HECTS hydrogels were biocompatible on a cellular level when the molar ratio of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> to catechol group was less than 0.5:1. The hydrogels prepared with a 0.125:1 molar ratio of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mrow><mml:mtext>IO</mml:mtext></mml:mrow><mml:mrow><mml:mn>4</mml:mn></mml:mrow><mml:mrow><mml:mo>-</mml:mo></mml:mrow></mml:msubsup></mml:math> -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.