Regeneration Matrix's technology, licensed from Georgia Tech, enables the design of a next generation nerve guide product to bridge large peripheral nerve gaps created due to trauma, tumor resection, or reconstructive surgery. The fundamental technology consists of a 'core'nanofiber based film, containing aligned biodegradable electrospun polymeric fibers (diameter 400-600nm), placed inside a tubular conduit. This 10 micron thick film occupies only 0.3% of the cross-sectional area of the nerve cuff/conduit and yet by facilitating efficient migration of host Schwann cells into the gap, significantly enhances the critical gap that can be bridged with conduits. Additionally, this fiber enhanced nerve guide (FE Nerve Guide) is able to bridge critically sized nerve gaps without the addition of any exogenous proteins, enabling its classification as a device and based on the predicate nerve cuffs, we are confident of their FDA approval as a device. Peripheral nerve injuries present a serious clinical problem. Around 250,000-300,000 peripheral nerve trauma cases are reported every year. The clinical gold standard for peripheral nerve repair uses nerves harvested from patient donor sites. These autografts are the best clinical bridging option available today;however, complications such as limited availability and neuroma formation reduce their appeal. Manufactured approaches use nerve cuffs (tubular conduits) alone which are technically approved for bridging gaps up to 30mm, but they are seldom used beyond 10mm gaps because of lack of efficacy. The FE Nerve Guide using nanoscaffold film(s) addresses this shortcoming in critically sized peripheral nerve gaps, and significantly enhances regeneration when compared to nerve cuffs. Having established the proof of concept with a polyacrylonitrile-methacrylate co-polymeric fibers, here we propose to evaluate a degradable fiber enhanced nerve cuff in phase I of this STTR application. Based on a freedom to operate analysis, we have have chosen to fabricate this device with polycaprolactone, a degradable polymer. Using rigorous histological, behavioral and electrophysiological techniques, in this phase I STTR application, we will evaluate the performance of a PCL-nanofiber enhanced PCL nerve conduit scaffold against a) the clinical gold standard, the autograft;and b) the leading nerve cuff in the market, the collagen NeuroGen nerve guide, using a critically sized 15mm peripheral nerve gap in a rodent model.
Over 250,000 peripheral nerve injuries occur every year in the US alone. This phase I study will facilitate the development of a new generation of nerve cuffs for the treatment of peripheral nerve injuries. We are confident that our biodegradable nerve cuff will perform significantly better than existing nerve conduits and substantially improve outcomes after peripheral nerve injury.
| Mokarram, Nassir; Merchant, Alishah; Mukhatyar, Vivek et al. (2012) Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials 33:8793-801 |
