Electroconductive hydrogels (ECHs) are highly hydrated 3D networks generated through the incorporation of conductive polymers, nanoparticles, and other conductive materials into polymeric hydrogels. ECHs combine several advantageous properties of inherently conductive materials with the highly tunable physical and biochemical properties of hydrogels. Recently, the development of biocompatible ECHs has been investigated for various biomedical applications, such as tissue engineering, drug delivery, biosensors, flexible electronics, and other implantable medical devices. Several methods for the synthesis of ECHs have been reported, which include the incorporation of electrically conductive materials such as gold and silver nanoparticles, graphene, and carbon nanotubes, as well as various conductive polymers (CPs), such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxyythiophene) into hydrogel networks. Theses electroconductive composite hydrogels can be used as scaffolds with high swellability, tunable mechanical properties, and the capability to support cell growth both in vitro and in vivo. Furthermore, recent advancements in microfabrication techniques such as three dimensional (3D) bioprinting, micropatterning, and electrospinning have led to the development of ECHs with biomimetic microarchitectures that reproduce the characteristics of the native extracellular matrix (ECM). In addition, smart ECHs with controlled structures and healing properties have also been engineered into devices with prolonged half-lives and increased durability. The combination of sophisticated synthesis chemistries and modern microfabrication techniques have led to engineer smart ECHs with advanced architectures, geometries, and functionalities that are being increasingly used in drug delivery systems, biosensors, tissue engineering, and soft electronics. In this review, we will summarize different strategies to synthesize conductive biomaterials. We will also discuss the advanced microfabrication techniques used to fabricate ECHs with complex 3D architectures, as well as various biomedical applications of microfabricated ECHs.

Myocardial infarction (MI) leads to a multi-phase reparative process at the site of damaged heart that ultimately results in the formation of non-conductive fibrous scar tissue. Despite the widespread use of electroconductive biomaterials to increase the physiological relevance of bioengineered cardiac tissues in vitro, there are still several limitations associated with engineering biocompatible scaffolds with appropriate mechanical properties and electroconductivity for cardiac tissue regeneration. Here, we introduce highly adhesive fibrous scaffolds engineered by electrospinning of gelatin methacryloyl (GelMA) followed by the conjugation of a choline-based bio-ionic liquid (Bio-IL) to develop conductive and adhesive cardiopatches. These GelMA/Bio-IL adhesive patches were optimized to exhibit mechanical and conductive properties similar to the native myocardium. Furthermore, the engineered patches strongly adhered to murine myocardium due to the formation of ionic bonding between the Bio-IL and native tissue, eliminating the need for suturing. Co-cultures of primary cardiomyocytes and cardiac fibroblasts grown on GelMA/Bio-IL patches exhibited comparatively better contractile profiles compared to pristine GelMA controls, as demonstrated by over-expression of the gap junction protein connexin 43. These cardiopatches could be used to provide mechanical support and restore electromechanical coupling at the site of MI to minimize cardiac remodeling and preserve normal cardiac function.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction (MI). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (GelMA) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof-of-concept study was to evaluate the cardioprotective potential of GelMA in a mouse model of MI. Methods and Results The physical properties of GelMA bioadhesive hydrogel were optimized in vitro. Impact of GelMA bioadhesive hydrogel on post-MI recovery was then assessed in vivo. In 20 mice, GelMA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI. An additional 20 mice underwent MI but received no GelMA bioadhesive hydrogel. Survival rates were compared for GelMA-treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post-MI were 89% for GelMA-treated mice and 50% for untreated mice (P=0.011). Left ventricular contractile function was better in GelMA-treated than untreated mice (fractional shortening 37% versus 26%, P<0.001). Average scar burden in GelMA-treated mice was lower than in untreated mice (6% versus 22%, P=0.017). Conclusions Epicardial GelMA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post-MI survival compared with control animals. In addition, GelMA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.