Electroactive and biocompatible fibrous
scaffolds have been prepared
and characterized using polyaniline (PAni) doped with dodecylbenzenesulfonic
acid (DBSA) combined with poly(lactic acid) (PLA) and PLA/poly(ethylene
glycol) (PEG) mixtures. The composition of simple and core–shell
fibers, which have been obtained by both uniaxial and coaxial electrospinning,
respectively, has been corroborated by Fourier-transform infrared
and micro-Raman spectroscopies. Morphological studies suggest that
the incorporation of PEG enhances the packing of PLA and PAni chains,
allowing the regulation of the thickness of the fibers. PAni and PEG
affect the thermal and electrical properties of the fibers, both decreasing
the glass transition temperature and increasing the electrical conductivity.
Interestingly, the incorporation of PEG improves the PAni-containing
paths associated with the conduction properties. Although dose response
curves evidence the high cytotoxicity of PAni/DBSA, cell adhesion
and cell proliferation studies on PLA/PAni fibers show a reduction
of such harmful effects as the conducting polymer is mainly retained
inside the fibers through favorable PAni···PLA interactions.
The incorporation of PEG into uniaxial fibers resulted in an increment
of the cell mortality, which has been attributed to its rapid dissolution
into the culture medium and the consequent enhancement of PAni release.
In opposition, the delivery of PAni decreases and, therefore, the
biocompatibility of the fibers increases when a shell coating the
PAni-containing system is incorporated through coaxial electrospinning.
Finally, morphological and functional studies using cardiac cells
indicated that these fibrous scaffolds are suitable for cardiac tissue
engineering applications.
The creation of cardiac tissue models for preclinical testing is still a non-solved problem in drug discovery, due to the limitations related to the in vitro replication of cardiac tissue complexity. Among these limitations, the difficulty of mimicking the functional properties of the myocardium due to the immaturity of the used cells hampers the obtention of reliable results that could be translated into human patients. In vivo models are the current gold standard to test new treatments, although it is widely acknowledged that the used animals are unable to fully recapitulate human physiology, which often leads to failures during clinical trials. In the present work, we present a microfluidic platform that aims to provide a range of signaling cues to immature cardiac cells to drive them towards an adult phenotype. The device combines topographical electrospun nanofibers with electrical stimulation in a microfabricated system. We validated our platform using a co-culture of neonatal mouse cardiomyocytes and cardiac fibroblasts, showing that it allows us to control the degree of anisotropy of the cardiac tissue inside the microdevice in a cost-effective way. Moreover, a 3D computational model of the electrical field was created and validated to demonstrate that our platform is able to closely match the distribution obtained with the gold standard (planar electrode technology) using inexpensive rod-shaped biocompatible stainless-steel electrodes. The functionality of the electrical stimulation was shown to induce a higher expression of the tight junction protein Cx-43, as well as the upregulation of several key genes involved in conductive and structural cardiac properties. These results validate our platform as a powerful tool for the tissue engineering community due to its low cost, high imaging compatibility, versatility, and high-throughput configuration capabilities.
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