Novel Coaxial Fibers Combining Piezoelectrical and Electrical Conductive Polymers towards Cardiac Tissue Engineering ^†

Electrical signals control cardiac mechanics using an excitation–contraction coupling mechanism that is present in cardiomyocytes from embryogenesis and early fetal development. In turn, the contraction activity of the heart influences the electrophysiological properties of cardiomyocytes by mechanoelectrical feedback. Through the combination of electrochemical signals from the autonomous nervous system and the elastic properties of the cardiac extracellular matrix, the excitation–contraction coupling mechanism is harnessed and cardiomyocytes can be induced to synchronously and continuously contract to pump blood out of the heart [1]. Hence, tissue engineering strategies capable of mimicking the electromechanical coupling of cardiac tissues are paramount to developing living cardiac patches for transplantation and more reliable in vitro disease models for cardiac diseases.

Electroconductive polymers and electrical stimulation have been investigated, aiming at developing smart scaffolds for cardiac regeneration [2]. Particularly, the electroconductivity of poly(aniline) (PANI) is greatly improved by chemical doping using camphorsulfonic acid (CSA) [3] and further enhanced by the use of optimised solvent systems [4]. However, current platforms to apply electrical stimulation in vitro, often require large external equipment, wires and electrodes, which limits the scalability and the in vivo application of these approaches.

Piezoelectric polymers are the key to overcoming these limitations due to their mechanoelectrical transduction properties, generating electrical stimulus when mechanically stimulated and vice versa (piezoelectricity). Poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) is one of the most promising piezoelectric materials, which owes its piezoelectric properties to a specific chain rearrangement identified through infrared spectroscopy as β-phase. Higher β-phase content correlates with increased piezoelectric properties of PVDF-TrFE and it can be increased through processing methods during electrospinning, as shown herein [5]. Hence, the combination of piezoelectric and electroconductive polymers into a scaffold with mechanoelectrical properties has the potential to produce and deliver electrical stimulation to cardiomyocytes, promoting their maturation. Such scaffold can be tailored to fibers using electrospinning, which structurally resemble the structure of the natural extracellular matrix and can further improve the cardiac cell phenotype.

In this work we propose a novel material-based approach to mimic the electromechanical coupling of cardiac tissues. Different electrospinning strategies were assessed to combine different polymers into monoaxial and coaxial nanofibers, including conjugated electroconductive (PANI:CSA), pizeoelectrical (PVDF-TrFE) and biodegradable polyesthers (poly(caprolactone) (PCL)). Various processing (e.g., voltage, flow rate) and solution (e.g., relative polymer ratio) parameters were optimised to obtain beadless and coaxial fibers. Fiber morphology, along with core-shell structure confirmation, was assessed by scanning electron microscopy. Fourier transform infrared data were used to simultaneously confirm the presence of the coaxial structure, quantify the β-phase content and infer the fiber’s piezoelectricity. Electroconductivity of the fibers was measured using the 4-probe method. Hydrophilicity was quantified by measuring the contact angle of the fibers using glycerol. Cellular studies using induced pluripotent stem cell-derived cardiomyocytes were performed and indicated better adhesion of the cells to the hydrophilic surfaces of the optimised coaxial fibers.

Overall, the coaxial electrospun fibers developed in this work expand the concept of electromechanical composites suitable for cardiac tissue engineering and, thus, contribute to the design of potential bioprosthetic implants to be transferred with in vitro cardiomyocytes and integrated in host tissues.