Magneto- and opto-stimuli responsive nanofibers as a controlled drug delivery system.

The drawbacks of conventional drug administration include repeated administration, non-specific biodistribution in the body's systems, the long-term unsustainability of drug molecules, and high global cytotoxicity, posing a challenge for the efficient treatment of chronic diseases that require varying drug dosages over time for optimal therapeutic efficacy. Most controlled-release methods encapsulate drug molecules in biodegradable materials that dissolve over time to release the drug, making it difficult to deliver drugs on a schedule. To address these limitations, we developed a magneto-, opto-stimuli responsive drug delivery system based on functionalized electrospun nanofibers loaded with superparamagnetic iron oxide nanoparticles (SPIONs). We exploited the Néel relaxation effect of SPIONs, where heat generated from vibrating SPIONs under exogenously applied magnetic fields or laser illumination induced structural changes of the thermo-sensitive nanofibers that encapsulate the particles. We showed that this structural change of nanofibers is the governing factor in controlling the release of dye molecules, used as a model drug and co-encapsulated within the nanofibers. We also showed that the degree of nanofiber structural change depends on SPION loading and duration of stimulation, demonstrating the tunability of the drug release profile. Overall, we demonstrated the potential of SPION-embedded thermoplastic nanofibers as an attractive platform for on-demand drug delivery.

Formation of 3D Self-Organized Neuron-Glial Interface Derived from Neural Stem Cells via Mechano-Electrical Stimulation.

Due to dissimilarities in genetics and metabolism, current animal models cannot accurately depict human neurological diseases. To develop patient-specific in vitro neural models, a functional material-based technology that offers multi-potent stimuli for enhanced neural tissue development is devised. An electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) nanofibrous scaffold is systematically optimized to maximize its piezoelectric properties while accommodating the cellular behaviors of neural stem cells. Hydro-acoustic actuation is elegantly utilized to remotely activate the piezoelectric effect of P(VDF-TrFE) scaffolds in a physiologically-safe manner for the generation of cell-relevant electric potentials. This mechano-electrical stimulation, which arose from the deflection of the scaffold and its consequent generation of electric charges on the scaffold surface under hydro-acoustic actuation, induces the multi-phenotypic differentiation of neural stem cells simultaneously toward neuronal, oligodendrocytic, and astrocytic phenotypes. As compared to the traditional biochemically-mediated differentiation, the 3D neuron-glial interface induced by the mechano-electrical stimulation results in enhanced interactions among cellular components, leading to superior neural connectivity and functionality. These results demonstrate the potential of piezoelectric material-based technology for developing functional neural tissues in vitro via effective neural stem cell modulation with multi-faceted regenerative stimuli.

Mechano-Responsive Piezoelectric Nanofiber as an On-Demand Drug Delivery Vehicle.

The control over biodistribution and pharmacokinetics is critical to enhance the efficacy and minimize the side effects of therapeutic agents. To address the need for an on-demand drug delivery system for precise control over the release time and the quantity of drugs, we exploited the mechano-responsiveness of piezoelectric poly(vinylidene fluoride-trifluroethylene) (P(VDF-TrFE)) nanofibers for drug delivery applications. The large surface area-to-volume ratio inherent to nanomaterials, together with the transformative piezoelectric properties, allowed us to use the material as an ultrasensitive and mechano-responsive drug delivery platform driven by the direct piezoelectric effect. The intrinsic negative zeta potential of the nanofibers was utilized to electrostatically load cationic drug molecules, where surface potential changes by exogenous mechanical actuation trigger the release of drug molecules. We show that the drug release kinetics of the P(VDF-TrFE) nanofibers depends on the fiber diameter, thus piezoelectric properties. We further demonstrated that the drug release quantity can be tuned by the applied pressure or dose of physiologically safe corporeal shockwaves as a mechanical stimulus in in vitro and ex vivo models. Overall, we demonstrated the utility of piezoelectric electrospun nanofibers for mechano-responsive controlled drug release.