Ultrasound-Activated Piezoelectric Polyvinylidene Fluoride-Trifluoroethylene Scaffolds for Tissue Engineering Applications.

Severe peripheral nervous system (PNS) injuries have limited options for therapeutic solutions to regain functional recovery. This can be attributed in part to the lack of regeneration pathways promoted by recapitulating chemical, physical, and electrical cues to direct nerve guidance. To address this, we examined ultrasonic stimulation of a piezoelectric polyvinylidene fluoride-triflouroethylene (PVDF-TrFE) scaffold as a potentially clinically relevant therapy for PNS regeneration. Owing to the piezoelectric modality of PVDF-TrFE, we hypothesize that ultrasound stimulation will activate the scaffold to electrically stimulate cells in response to the mechanical deformation mediated by sound waves. Biocompatible PVDF-TrFE scaffolds were fabricated to be used as an ultrasound-activated, piezoelectric biomaterial to enhance cellular activity for PNS applications. NIH-3T3 fibroblasts were cultured on PVDF-TrFE nanofibers and stimulated with low-, medium-, or high-powered ultrasound. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays were performed on fibroblasts to measure the metabolic activity of the cells following stimulation. MTT assays showed that ultrasound-stimulated fibroblasts on PVDF-TrFE scaffolds had increased metabolic activity as power was increased, whereas on plain polystyrene, an opposite trend was observed where cells had a decreased metabolic activity with ascending levels of ultrasound power. Ultrasound-stimulated PVDF-TrFE nanofibers hold exciting potential as a therapy for PNS injuries by promoting increased metabolic activity and proliferation. The ability to noninvasively stimulate implantable piezoelectric nanofibers to promote mechanical and electrical stimulation for nerve repair offers a promising benefit to severe trauma patients.

Innervation of an Ultrasound-Mediated PVDF-TrFE Scaffold for Skin-Tissue Engineering.

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.