A π-π conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction

Previous studies suggested that a stiffer hydrogel system exhibited a better performance to promote heart function after myocardial infarction (MI). However, the nature of myocardium, a tissue that alternately contracts and relaxes with electrical impulses, leads us to hypothesize that a soft and conductive hydrogel may be in favor of mechanical and electrical signals transmission to enhance heart function after MI. In this work, pi-pi conjugation interaction was first employed to produce a soft injectable hydrogel with conductive property. Melamine with pi-pi conjugation ring was used as a core to synthesize a multi-armed crosslinker PEGDA700-Melamine (PEG-MEL), which could crosslink with thiol-modified hyaluronic acid (HA-SH) to form an injectable hydrogel rapidly. By incorporating graphene oxide (GO), the injectable PEG-MEL/HA-SH/GO hydrogel exhibited a soft (G' = 25 Pa) and anti-fatigue mechanical property and conductive property (G = 2.84 x 10(-4) S/cm). The hydrogel encapsulating adipose tissue-derived stromal cells (ADSCs) was injected into MI area of rats. The significant increase in cc Smooth Muscle Actin (alpha-SMA) and Connexin 43 (Cx43) expression confirmed that the gel efficiently promoted the transmission of mechanical and electrical signals. Meanwhile, a significant improvement of heart functions, such as distinct increase of ejection fraction (EF), smaller infarction size, less fibrosis area, and higher vessel density, was achieved. (C) 2017 Elsevier Ltd. All rights reserved.