NervAlign® Nerve Cuff

The ReNerve NervAlign^® Nerve Cuff is a pliable, semi-permeable, resorbable membrane made of collagen designed to protect traumatised but intact nerves, sutured and short gap nerve repairs where ends have been re-approximated and suture sites of nerve grafts. The tissue product is biodegradable and protects from scarring and excess inflammation, while allowing nutrients and neurotrophic factors to pass through to facilitate nerve repair. The product also has the potential to be used in conjunction with cell therapies to enhance patient recovery. As a result, the NervAlign^® Nerve Cuff can be used in a wide range of nerve repair and nerve replacement surgical procedures.

The NervAlign^® Nerve Cuff has recently received market clearance in the USA via the 510(k) pathway.

The ReNerve NervAlign^® Nerve Cuff manufacturing process has been developed and scaled for commercial production and therefore the cost of goods sold (COGs) are extremely competitive relative to the list prices of the competing products.

The NervAlign^® Nerve Cuff would be used either alone as a protective wrap around cut, damaged, inflamed or replaced nerves, or in combination with the ReNerve Nerve Graft and the ReNerve ‘bionic’ nerve replacement, to protect the suture site of implanted grafts. The cuff can also be used in nerve transfer and ‘super charging’ procedures and harvested grafts. The benefits of the NervAlign^® Nerve Cuff are:

• Semipermeable – allows small-sized nutrients and neurotrophic factors to pass through yet provides a barrier to scar forming cells. Remodelling and neovascularisation in the fascia surrounding tissue of the exterior of the nerve cuff.
• Highly biocompatible – porcine Type 1 collagen is non-inflammatory and generally non immunogenetic.
• Completely absorbable – collagen matrix is degraded and resorbed by normal metabolic processes leaving behind the repaired nerve.
• Easy to use – NervAlign^® Nerve Cuff can be used as a flat or tubular implant to protect repaired nerve injuries. The NervAlign^® Nerve Cuff is very pliable and conforms to shape for easy positioning around transected nerves repaired with tension-less nerve repair techniques.
• Non-toxic manufacturing process – important with changing requirements for devices used in theatre. No ethylene oxide sterilisation.
• Antigen free – No contaminating nuclei.

The NervAlign® Nerve Cuff will bring initial revenues into the company and allow for brand building in the marketplace. In the future, NervAlign® Nerve Cuff will be sold together with the company’s nerve graft (subject to successful clinical trials) and replacement nerves.

Current clinical practice and limitations

When direct repair of an injured nerve is not possible or the gap is too large, the damaged ends are excised, and the resulting gap is bridged by a healthy nerve graft harvested from the same patient (autologous).  Surgeons commonly remove a segment of the sural nerve which is a purely sensory nerve that is in the foot. This not only requires an additional procedure, but it also results in permanent sensory loss (numbness) and can also lead to painful neuroma formation. Furthermore, the diameter and structure of the harvested nerve does not always match that of the damaged nerve requiring repair and such size mismatch may lead to suboptimal repair.  In patients with significant injuries where long segments/multiple nerves require grafting, the availability of healthy autologous nerves may be limited.

Because of the above limitations alternative conduits have been developed including decellularised human allografts (e.g. Axogen’s Avance), conduits derived from bovine collagen and a number of synthetic alternatives derived from polyglycolic acid (PGA) or polylactide caprolactones (PLCL).  Axogen’s Avance conduit product (processed nerves that are harvested from human cadavers, available as an “off the shelf” alternative and currently in surgical use) have shown most commercial promise, but availability of cadaveric tissue is severely limited and may require cross-typing.

Advantages of a processed nerve xenograft (NervAlign® Nerve Graft) over autologous nerve grafts

1. Unlimited availability of xenograft material of required length and diameter to match the required repair.
2. No need for a secondary procedure to harvest autologous nerve grafts. This eliminates the inevitable sensory/motor deficits attributed to autologous nerve harvest as well as all the associated procedural risks and complications e.g. wound infection, neuroma formation, neuropathic pain, and scar formation.
3. Shorter operating time.
4. Theoretical advantage of “pre-degeneration”. A xenograft that has already undergone in-vitro degeneration through the cleaning processing method may, in theory, expedite re-innervation by allowing immediate commencement of regeneration following implantation, thereby by-passing the requirement for in vivo Wallerian degeneration.

ReNerve has developed proprietary methods to produce xenograft nerve grafts sourced from animal tissue with a view to obviate the need to harvest and use autologous tissue.

The NervAlign® Nerve Graft is designed to be readily available “off the shelf” and allow immediate nerve regeneration once implanted with no secondary surgery required. The NervAlign® grafts come in various diameter sizes to allow surgeons to better match donor and recipient nerves for size and diameter, thereby allowing for better repair and improved surgical outcomes. ReNerve proprietary methods were developed to thoroughly decellularise the tissue yet retain its structure such that the resulting cleaned scaffold that guides nerve regrowth should not be recognised as a foreign tissue and eliminates the risk of rejection.

ReNerve ‘bionic’ Nerve Graft

ReNerve, in collaboration with CSIRO, is developing a ‘bionic’ nerve graft to repair longer nerve gaps and offer further customisation of nerve grafts. ReNerve is leveraging its own knowledge and proprietary technologies with those the CSIRO has developed over the past 12 years. The initial prototypes will assess a combination of natural collagen and polymer technologies, with the goal to have an ‘off-the-shelf’ nerve that can be cut to measure to replace damaged nerves. Currently there is no effective option for surgeons in the replacement of longer nerves (>3-5 cm), with current options (donor or autologous tissue) providing inconsistent, less than optimum outcomes. ReNerve is also currently working with material science engineers at Monash University to develop additional surface patterned synthetic nerve repair materials.

Dura mater replacement

A recent development for ReNerve has been the growing understanding of the potential to apply Reserve’s technology as a Dura mater replacement. Dura mater is the outermost layer of the three meninges (connective tissue layers) that surround and protect the brain and spinal cord. ReNerve plans to develop two products for the replacement of dura mater.

Product one:

• Short term, remodeling dura replacement
• For small craniotomies and back/spinal surgery
• Based on the nerve cuff eCOO Technology
• Designed to be sutured in place to allow for remodeling repair
• Very clean and avoids the chemical meningitis seen with other products

Product two:

• Long term dura replacement
• Multi-functional product
• Sealed, anti-adhesion product for all craniotomies and spinal surgery
• Antibacterial to prevent surgical site infections

Operating room treatment kit

In discussions with surgeons, some have asked if the ReNerve proprietary graft treatment process could be modified for use in theatre for patient harvested tissue. As a result, ReNerve is developing an Operating Room Treatment Kit that would allow surgeons to treat harvested tissue post-harvest, prior to surgical implant. Following injury, and as part of the healing process, the nerve initially undergoes “Wallerian degeneration” so that existing nerve components break down and are cleared by the body before regeneration can occur. The purpose of the Operating Room Treatment Kit would be to remove the ‘excess’ material from the harvested tissue leaving a cleaner scaffold ready for repopulation and remodelling by cells appropriate to the area in which it is used so that recovery can be expedited. Cleaner scaffold ready for repopulation and remodelling by cells appropriate to the area in which it is used so that recovery can be expedited.

Although the Operating Room Treatment Kit was initially developed to target harvested nerve tissue, to date ReNerve has used the kit on nerve tissue, tendon and cardiovascular tissue, therefore making it a universal tissue theatre kit that can be used across a large range of surgical procedures globally.

ReNerve and Vivazome announced a collaboration to combine the ReNerve NervAlign® Nerve Cuff and the Vivazome exosome technology for the treatment of spinal cord injury. VivaZome Therapeutics Pty Ltd is a privately held Australian biotech company which aims to develop and commercialise exosome-based therapies for debilitating and/or life-threatening disorders.

The companies will explore the use of the clean, protective, nerve guiding NervAlign® scaffold to deliver regenerative purified exosomes from selected cell types locally to the area of spinal cord injury. On implantation, the loaded scaffold matrix should release the exosomes into the local, protected environment and the additional restorative effect of the combined products on the damaged spinal cord will be measured. Initial focus will be on ischemia, fibrotic disease and neurological disorders.