No abstract

Applied electric fields (EFs) have previously been presented as a potential method of inducing functional recovery after neural trauma. To date, most of this research has focused on the application of a direct current (DC) stimulus to produce the desired EF and induce neuronal growth. We propose that high duty-cycle alternating current (AC) stimulation is capable of inducing similar EFs within the spinal cord and eliciting a neural response with the added benefits of increased field propagation and lower power consumption. Through ex vivo tissue testing of porcine spinal columns and Xenopus laevis cell cultures, 80% duty-cycle AC stimulation was compared to DC stimulation for efficacy in field generation and induction of neurite growth. Results from ex vivo measurement show that AC stimulation is capable of producing EFs of greater magnitudes over an increased distance in the spinal cord than DC stimulation at the same current magnitude. Furthermore, stimulation of Xenopus laevis neuronal cultures with 80% duty-cycle rectangular waves indicated a significant increase in neurite length as compared to non-stimulated controls and cathodal preference, growth that was statistically similar to DC-stimulated cells. These results suggest high duty-cycle stimulation modalities to be applicable and perhaps preferable to DC stimulation in electrically mediated neuronal therapies.

Proof-of-concept studies that display the potential of using a glucose-sensitive hydrogel as a continuous glucose sensor are presented. The swelling ratio, porosity, and diffusivity of the hydrogel increased with glucose concentration. In glucose solutions of 50, 100, 200, and 300 mg/dL, the hydrogel swelling ratios were 4.9, 12.3, 15.9, and 21.7, respectively, and the swelling was reversible. The impedance across the hydrogel depended solely on the thickness and had an average increase of 47 Ω/mm. The hydrogels exposed to a hyperglycemic solution were more porous than the hydrogels exposed to a normal glycemic solution. The diffusivity of 390 Da MW fluorescein isothiocyanate in hydrogels exposed to normal and hyperglycemic solutions was examined using fluorescence recovery after photobleaching and was found to be 9.3 × 10−14 and 41.4 × 10−14 m2/s, respectively, compared to 6.2 × 10−10 m2/s in glucose solution. There was no significant difference between the permeability of hydrogels in normal and hyperglycemic glucose solutions with averages being 5.26 × 10−17 m2 and 5.80 × 10−17 m2, respectively, which resembles 2–4% agarose gels. A prototype design is presented for continuous intravascular glucose monitoring by attaching a glucose sensor to an FDA-approved stent.

Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. Furthermore, cultures of chick dorsal root ganglia in gels of hyaluronic acid or chondroitin sulfate revealed enhanced growth in chondroitin sulfate gels only upon addition of peptide. Taken together, these results suggest a synergistic nerve growth factor-binding activity between this peptide and chondroitin sulfate.