Our research centers in the understanding of the mechanism involved in axon guidance and target recognition during development, and after injury, and the application of this knowledge in translational applications. Specific projects include: spinal cord injury and neuroprotection, peripheral nerve gap repair, neuroma prevention, and regenerative peripheral neurointerfaces for the control and feel or robotic prosthetic limbs. Our areas of research are shown in the following sections.
Areas of Research
Peripheral Nerve Interfacing
Advanced robotic prosthesis are capable of performing complex movements, and equipped with multiple proprioceptive and exteroceptive sensors and embedded controllers for implementing automatic grasp control and for potentially delivering sensory feedback to the amputee. We developed a non-obstructive regenerative multielectrode interface (REMI), which is placed between the transected ends of an end-toend repaired nerve, and has been successful in obtaining single and multiunit recordings. The REMI was shown to record action potentials as early as 7 days post implantation with high signal-to-noise ratio, for as long as 3 months in some animals. We then developed a new strategy for modality-specific neural interfacing in the PNS. Instead of relying on the physical design of the electrode array and/or the differential electrical stimulation of a mixed nerve, our strategy is based on the use of developmental and regenerative molecular guidance cues to separate specific neuron-types from a mixed population, and to compartmentalize and stabilize the neuron-electrode interface. In collaboration with Dr. Phil Troik at IIT, we have recently developed a miniaturized wireless electrode array for peripheral nerve stimulation, which has
been working continuously in vivo for almost a year.
been working continuously in vivo for almost a year.
Peripherarl Nerve Regeneration
Nerve gap injuries remain a significant clinical problem, as current nerve guides do not provide results better than autografts, particularly for long gaps. We developed a biosynthetic nerve implant that offers a multiluminal scaffolds with luminar attractants to entice nerve repair across a gap defect. Neurotrophic factors (NTF) such as NGF, BDNF, and NT-3, as well as GDNF, play an important role in axonal regeneration. However, Current NTF delivery methods do not provide sustained three-dimensional molecular gradients and extracellular matrix support for optimal axonal elongation and directed growth. We recently developed a method capable of establishing sustained 3D NTF gradients in the collagen-filled lumen of multi-luminal nerve guides by placing biodegradable polymeric fibers on the wall of the microchannels. Neurons growing in microchannels exposed to a NGF gradient showed an increase in axonal length compared to those treated with a linear growth factor concentration. This device has a patent pending protection and is currently licensed by Tissue Gen Co.
Anecdotal and clinical reports have suggested that radio-frequency electromagnetic fields (RF EMFs) may serve as a trigger for neuropathic pain. However, these reports have been widely disregarded, as the epidemiological effects of electromagnetic fields have not been systematically proven, and are highly controversial. Here, we demonstrate that anthropogenic RF EMFs elicit post-neurotomy pain in a tibial neuroma transposition model. Behavioral assays indicate a persistent and significant pain response to RF EMFs when compared to SHAM surgery groups. Laser thermometry revealed a transient skin temperature increase during stimulation. Furthermore, immunofluorescence revealed an increased expression of temperature sensitive cation channels (TRPV4) in the neuroma bulb, suggesting that RF EMF-induced pain may be due to cytokine-mediated channel dysregulation and hypersensitization, leading to thermal allodynia. Additional behavioral assays were performed using an infrared heating lamp in place of the RF stimulus. While thermally-induced pain responses were observed, the response frequency and progression did not recapitulate the RF EMF effects. In vitro calcium imaging experiments demonstrated that our RF EMF stimulus is sufficient to directly contribute to the depolarization of dissociated sensory neurons. Furthermore, the perfusion of inflammatory cytokine TNF-α resulted in a significantly higher percentage of active sensory neurons during RF EMF stimulation. These results substantiate patient reports of RF EMF-pain, in the case of peripheral nerve injury, while confirming the public and scientific consensus that anthropogenic RF EMFs engender no adverse sensory effects in the general population.
sPINAL CORD INJURY
Scoliosis corrective surgery requires the application of multidirectional stress forces to the spinal cord, including those of distraction. We have designed an innovative device that relies on intervertebral grip fixation and computer controlled linear actuators to induce bidirectional distraction injuries to the spine. Treatment of painful neuromas is frequently a challenge even for experienced peripheral nerve surgeons. Moreover, neuroma mediated pain can also be elicited by radiofrequency electromagnetic radiation (EMR). Furthermore, no animal model has been reported to replicate such EMR induced neuroma pain, and no current treatment incorporates strategies to reduce EMR to the neuroma. We recently establish an animal model for EMR neuroma pain and developed a “neuroma blocker” device specifically designed to prevent neuroma formation and block EMR induced pain.