Investigation of Nerve Specific Hydrogel in Rat Model

INTRODUCTION Often, when one experiences trauma or undergoes an invasive surgery, peripheral nerve damage results. Each year 360,000 people in the United States suffer from peripheral nerve injury [1]. Peripheral nerve injury can result in a loss of sensory and or motor function and will often lead to long-term disability in patients [2]. When a peripheral nerve is compressed or severed, the injured section of the nerve undergoes Wallerian degeneration until a gap has formed, separating the proximal and distal ends of the nerve and leaving a nerve gap [3]. When nerve gaps are too large (>15mm) for a surgeon to repair effectively by suturing the proximal end of the nerve to the distal end, there are two standard modes of repair: an autologous nerve graph and the use of a nerve conduit. In the use of autologous nerve graphs to replace the missing nerve the nerve gap, a section of a nerve from the patients own body, usually the seural nerve which runs down the back of the leg. The section of nerve removed is then sutured in place of the degenerated nerve. The autologous nerve graft method currently used is less than satisfactory, as the seural nerve is a sensory nerve, and leg sensation can be lost as a result of the surgery. The alternative, the use of a nerve conduit has been shown to have positive effects in the nerve regeneration, as it is used as a guide to help the axons of the severed nerve grow outward from the proximal end until it meets the distal end of the severed nerve. The nerve guide is effective in preventing wayward nerve growth. Its tubular shape allows nerve axons to grow straight toward the distal end rather than branching out with no specific direction. While the autologous nerve grafts and use of nerve conduits are effective in assisting axons in growth between the nerve gaps, the outcome of nerve repair with these treatments is determined by the location of the injury of the injury and the time delay before treatment and fully functional recovery is rare [4]. Many researchers have been working to improve the functionality of regenerated nerves by not only using nerve conduits but by introducing various modifications to the conduits including addition of growth factors, supportive cells, and internal frameworks. The Brown Lab at the University of Pittsburgh has focused on the use of an internal framework and growth factors to modify a nerve conduit. We have done this by developing a nerve specific hydrogel derived from healthy porcine sciatic nerve. The nerve removed of DNA leaving behind only the extracellular matrix, which is an internal framework including growth factors that recruit Schwann cells similar to urinary bladder matrix hydrogels that have been used for regeneration of other types of tissue. Schwann cells are an integral component of nerve regeneration. The hydrogel begins as a liquid and becomes a gel at physiological temperature. Having peripheral nerve origin, the gel it maintains growth factors specific to nerves, and the hydrogel is hoped to have a positive effect on nerve regeneration [5]. To test the effectiveness of our product in vivo, we created a rat model in which the sciatic nerve was axially severed, creating a 15mm gap to simulate a severed nerve in a human. In study rats, our hydrogel was inserted into a conduit sutured to the ends of the severed nerve and taken out to 7, 14, 28, and 90day time points. The control models were similar but had saline injected in the conduits rather than our hydrogel. To gain preliminary results, we excised and imaged a 28-day rat and imaged the nerve regrowth as shown in Figure 1.