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In this work, electrospun polyvinylidene-trifluoroethylene (PVDF-TrFE) was utilized for its biocompatibility, mechanics, and piezoelectric properties to promote Schwann cell (SC) elongation and sensory neuron (SN) extension. PVDF-TrFE electrospun scaffolds were characterized over a variety of electrospinning parameters (1, 2, and 3 h aligned and unaligned electrospun fibers) to determine ideal thickness, porosity, and tensile strength for use as an engineered skin tissue. PVDF-TrFE was electrically activated through mechanical deformation using low-intensity pulsed ultrasound (LIPUS) waves as a non-invasive means to trigger piezoelectric properties of the scaffold and deliver electric potential to cells. Using this therapeutic modality, neurite integration in tissue-engineered skin substitutes (TESSs) was quantified including neurite alignment, elongation, and vertical perforation into PVDF-TrFE scaffolds. Results show LIPUS stimulation promoted cell alignment on aligned scaffolds. Further, stimulation significantly increased SC elongation and SN extension separately and in coculture on aligned scaffolds but significantly decreased elongation and extension on unaligned scaffolds. This was also seen in cell perforation depth analysis into scaffolds which indicated LIPUS enhanced perforation of SCs, SNs, and cocultures on scaffolds. Taken together, this work demonstrates the immense potential for non-invasive electric stimulation of an in vitro tissue-engineered-skin model.
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Formation of 3D Self‐Organized Neuron‐Glial Interface Derived from Neural Stem Cells via Mechano‐Electrical Stimulation
Abstract 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.
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- Award ID(s):
- 1805975
- PAR ID:
- 10449441
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Healthcare Materials
- Volume:
- 10
- Issue:
- 19
- ISSN:
- 2192-2640
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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