In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells
are seeded within three-dimensional porous scaffolds to create functional
cardiac patches. However, current cardiac patches do not allow for online
monitoring and reporting of engineered-tissue performance, and do not interfere
to deliver signals for patch activation or to enable its integration with the
host. Here, we report an engineered cardiac patch that integrates cardiac cells
with flexible, free-standing electronics and a 3D nanocomposite scaffold. The
patch exhibited robust electronic properties, enabling the recording of cellular
electrical activities and the on-demand provision of electrical stimulation for
synchronizing cell contraction. We also show that electroactive polymers
containing biological factors can be deposited on designated electrodes to
release drugs in the patch microenvironment on-demand. We expect that the
integration of complex electronics within cardiac patches will eventually
provide therapeutic control and regulation of cardiac function.
Although cardiac patches hold a promise for repairing the infarcted heart, their integration with the myocardium by sutures may cause further damage to the diseased organ. To address this issue, we developed facile and safe, suture-free technology for the attachment of engineered tissues to organs. Here, nanocomposite scaffolds comprised of albumin electrospun fibers and gold nanorods (AuNRs) were developed. Cardiac cells were seeded within the scaffolds and assembled into a functioning patch. The engineered tissue was then positioned on the myocardium and irradiated with a near IR laser (808 nm). The AuNRs were able to absorb the light and convert it to thermal energy, which locally changed the molecular structure of the fibrous scaffold, and strongly, but safely, attached it to the wall of the heart. Such hybrid biomaterials can be used in the future to integrate any engineered tissue with any defected organs, while minimizing the risk of additional injury for the patient, caused by the conventional stitching methods.
Controlled release systems are often integrated into polymeric scaffolds to supply essential biofactors to trigger physiological processes in engineered tissues. Here, we report the modification of chondroitin sulfate (CS) electroactive polymer with gold nanorods (AuNRs) to create hybrid macroporous scaffolds for enhanced on-demand release of growth factors and cytokines. The mechanical properties, porosity and degradation of the hybrid scaffolds were evaluated, and the viability and functionality of seeded cardiac cells were assessed. Following, the ability to control the release of the enzyme lysozyme, and the cytokine, stromal cell-derived factor 1 (SDF-1) by applying electrical stimulation, was demonstrated. The AuNRs were able to increase the current through the scaffolds, providing an efficient on–off release profile of SDF-1, which resulted in higher migration of cells expressing CXCR4 receptor. Finally, the engineered scaffolds were transplanted in rats and SDF-1 was released daily by electrical stimulation, promoting blood vessel-forming cell infiltration and vascularization. We envision that gold nanoparticles and other conducting nanomaterials can be incorporated into different electroactive materials to improve their capabilities not only for tissue engineering applications, but for a variety of biomedical applications, where enhanced electrical stimulation is needed.
Graphical Abstract
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