Research

Neurotrophic factors (NTF) such as NGF, BDNF, and NT-3, as well as GDNF, play an important role in axonal regeneration. To provide sustained three-dimensional molecular gradients and extracellular matrix support we developed a method capable of establishing sustained 3D NTF gradients in the collagen-filled lumen of multi-luminal nerve guides and showed that NGF gradient increased axonal length. This device was patented and licensed to Tissue Gen Inc. We recently demonstrated that PTN and GDNF synergistically stimulate nerve regeneration across 3 and 4 cm long-gap injuries. On SCI we demonstrated for the first time that NGF can overcome the inhibitory nature of the CNS and demonstrated the neuroprotective role of Riluzole in an unique animal model of atraumatic spine distraction injury.

We developed a non-obstructive regenerative multielectrode interface (REMI), placed between the transected ends of an end-to- end to record motor intent from amputated nerves, and deliver sensory feedback from robotic limb prosthetic devices. A further development on the REMI was the use of growth factors in a Y-shape conduit for modality-specific neural interfacing in the PNS. We have reported a miniaturized wireless 16-electrode array for peripheral nerve stimulation, which worked reliably continuously in vivo for more than 14 months. We also assist in the development of a sub-millimeter wireless stimulator and recently demonstrated that this device can be attached to commercial nerve cuff electrodes for wireless neural stimulation. Since commercial cuff electrodes are made with relatively thick silicone conduits, we also reported the fabrication of 16-electrode arrays using a thin film softening polymers that are cause significantly less fibrosis compared to silicone cuff electrodes. Recently we have reported the development of amorphous silicon carbide ultramicroelectrode arrays (a-SiC UMEAs) to provide selectivity in the recording of neural activity in peripheral nerves.

We have been interested in developing testing new materials that can improve the conductivity and safety of peripheral nerve interfaces. We first reported the use of carbon nanotubes as material for neural stimulation/recording. We then showed that platinized graphene fibers have significantly lower impedance and increased charge injection capacity compared to Pt electrodes. We have also been interested in developing new medical applications for neural interfacing. We have shown that stimulation of somatic nerve fascicles can effectively reduce the mean arterial pressure in genetically hypertense rats, and that stimulation of motor nerves controlling individual pelvic floor muscles can be used as a treatment for stress urinary incontinence and detection of neural activity in the cVN related to changes in systemic oxygenation and blood pressure. We also demonstrated that stimulation of pelvic floor nerves can increase the urethral pressure and reverse bladder efficiency deficits in old multiparous rabbits, an accepted model for SUI.

During development axons are guided to their targets via membrane bound and secreted molecular cues, which can be either attractive or repulsive. We uncovered the role of NT-3 in proper targeting of thalamic neurons projecting to the primary sensory cortex, defined the role of Klf7 in the regulation of nociceptive neuron development, and discovered that Ephrin B-3 plays a critical developmental role in the proper targeting of axonal projections from the primary motor cortex to the ventral motor neurons in the spinal cord. We then discovered that EB-3 is upregulated in oligodendrocytes early postnatally and reported for the first time that this molecule is a myelin-associated inhibitor in the adult spinal cord. More recently, we uncovered the role of the Ephrin ligands in guiding the migration of CA-3 hippocampal neurons from their birth site in the sub-ventricular zone.