Development of Electrically Conductive Double‐Network Hydrogels via One‐Step Facile Strategy for Cardiac Tissue Engineering

Abstract

Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one-step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene-3-acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo-crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10(-4) S cm(-1)) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose-derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.

Superaligned Carbon Nanotubes Guide Oriented Cell Growth and Promote Electrophysiological Homogeneity for Synthetic Cardiac Tissues

“…By seeding cardiac cells onto scaffolds and nurturing their growth in vitro, engineered tissues are expected to generate natural heart structures and functions and can be transplanted to replace fibrous scars . Precisely designed scaffolds have been used to organize cells into functional tissues, as in the cases of polymer scaffolds with special structures that guide morphologies of cultured cells and the use of conductive components that improve internal cardiac electrical connections . In fact, the natural myocardium possesses a hierarchically aligned structure with different layers .…”

Nanoreinforced Hydrogels for Tissue Engineering: Biomaterials that are Compatible with Load‐Bearing and Electroactive Tissues

“…One of the most accepted paradigms in cardiac‐tissue engineering is the fabrication of 3D scaffolds that can guide cardiac progenitor cells to form ex vivo “patches” or new in vivo tissue for the reparation of damaged myocardium . Some of the fundamental requirements for an ideal tissue‐engineering scaffold for cardiac regeneration are biodegradability, porosity, and mechanical/electrical properties matching those of healthy cardiac tissue . Nanocomposite hydrogels containing conductive nanomaterials represent an attractive multifunctional platform for cardiac regeneration, offering a combination of all these properties .…”

“…However, as a critical limitation, conventional engineering scaffolds cannot mimic the native properties of load‐bearing (ligaments, bone, cartilage, tendon, and bone) and electroactive tissues (cardiac, skeletal muscle, brain, and nerve) in the body ( Figure ). In fact, most of the current scaffolds are rigid insulators and therefore do not meld well with the elastic, dynamic, and electroactive organs of the body . Neither do they mimic the complex architecture of native tissues, nor do they provide the needed mechanical, electrical, and biology stimuli for orchestrating cells into mature and functional tissues.…”

“…Of the many commercially available scaffolding biomaterials, hydrogels are one suitable candidate for tissue engineering as they provide a biomimetic and hydrated 3D microenvironment to support cell function . In simple terms, these gels are largely made up of water (usually ≥ 90%) and their network‐building blocks can be numerous, spanning from purely natural to purely synthetic polymers – a variety that enables tailor‐made hydrogels .…”

Incorporation of Conductive Materials into Hydrogels for Tissue Engineering Applications

“…This is integrated with the materials that make up the biocompatible hydrogel, and diffusion may proceed to be transmitted to cells. Luo et al developed a method for producing PPy by using controlled nano-porous structures to release controlled dexamethasone in response to an electric current [155]. Wang et al prepared an electrodeposited AuNP conductive hydrogel by adopting a crosslinking method using 1,3,5-benzenetricarboxylic acid as a ligand and Fe3+ as a metal ion ( Figure 13) [156].…”