NJCBM has ben involved in multiple NEUROSCIENCE INITIATIVES, working in cutting-edge areas of research and collaboration across both the central and peripheral nervous systems. Here are examples of presently running activities.
A braided kink-resistant degradable conduit to be applied in nerve gap-injury and post-amputation neuroma
Peripheral nerves may suffer from a complete resection that leaves an empty gap between the stumps. These gap-injuries can be treated by implanting a bridging nerve-guidance-conduit (NGC) that will provide a protected environment where nerve fibers can regenerate and reconnect. This engineered treatment avoids the limitations of the traditional autografting procedure, which requires the sacrifice of another nerve from the same patient but still not guarantee a full recovery (so, in the worst case, the patients can end up with two lesions, instead of one). Nerve-guidance-conduit are effective on gap lengths about 20 mm or shorter and they are mostly applied in lesions of the digital nerves of the hand.
When an amputation occurs, however, there is only one nerve stump that remains and, so, regenerating fibers grow in a whirling fashion without a distal target and produce a “neuroma”, a disordered assembly of nerve fibers entangled with fibrous tissue. Neuroma can be the source of a severe chronic pain that can limit greatly the patient activities and very negatively affect the quality of life. In this case, the protected environment provided by a long capped-conduit can help in decreasing its occurrence.
The specific characteristics provided by the NGC developed at NJCBM will be of help in both instances. The unique degradable polymer and braiding technology of the NJCBM NGC allow for a kink resistance and optimal degradation time. They have been tested in multiple in-vivo model in the rat, rabbit and pig. These studies have been funded by several sources, the most notable of which is the NIH-NINDS (National Institute of Neurological Disorders and Stroke).
A 44 mm long Tyrosine-derived poly-carbonate conduit is going to be micro-surgically implanted in an experimental lesion in the rabbit sciatic nerve.
Device-assisted controlled biophysical environment for spinal cord regeneration
Spinal cord injuries (SCI) are lifelong severe de-habilitating injuries. The surgical repair of transection of the spinal cord is an unmet clinical need. A surgical procedure centered on an implantable degradable device able to provide a suitable biophysical environment to protect and guide spinal cord regeneration was developed at NJCBM. This was done trying to translate the experience in peripheral nerve injury to SCI. There are, however, profound biological differences between spinal cord regeneration and peripheral nerve regeneration and the spinal cord anatomy poses great challenges in the surgical implantation of artificial devices. NJCBM is testing a novel strategy based on a 3D-printed degradable device thanks to a grant awarded by the NJCSCR (New Jersey Commission on Spinal Cord Research). The animal model is the New Zealand White Rabbit.
In vitro study of the myelination process in the “suspended wire model”
Axons prolonging from neuronal cells are ensheathed by the “myelin”, a multiple membrane wrapping provided by specific cells: the Oligodendrocytes present in the Brain and Spinal Cord, and the Schwann cells present in peripheral nerves.
The process of myelination is affected by traumatic lesions or by demyelinating diseases (like Alzheimer) and a lot of studies are presently conducted to find a way to re-established this process once it has been disrupted. It is difficult, however, to study the biology of isolated myelinating cells in-vitro because they need a neuronal axon to express their myelinating capability.
At NJCBM a unique in-vitro system has been developed to culture myelinating cells on microscopic wires that act as “artificial axons” and are suspended in the liquid culture media. These studies have been supported by the NJHF (New Jersey Health Foundation).
Schwann cells are elongating on a Carbon fiber (nucleus in blue; cytoplasm in green).
Oligodendrocytes (nucleus in blue; cytoplasm in red) and an Astrocytes (in yellow) are present on a suspended network of artificial axons (study performed in cooperation with Dr. Cheryl Dreyfus, RWJMS).