Bridging peripheral nerve gaps with conduits for enhanced nerve regeneration
Inventors
Woods, Alexander • PLOWRIGHT, Robyn • VOLLRATH, Friedrich
Assignees
Publication Number
US-11602348-B2
Publication Date
2023-03-14
Expiration Date
2041-07-08
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Abstract
Disclosed herein are compositions comprising containers and silk elements. Disclosed herein are methods of regenerating an at least partially severed nerve cell. Disclosed herein are compositions for regenerating an at least partially severed nerve cell.
Core Innovation
The invention disclosed provides medical devices comprising containers configured to encourage the regrowth of at least a portion of a nerve cell in vivo within the container. These devices include features such as flexibility, permeability to allow nutrient influx and waste outflow through openings, and an interior element comprising fibers or filaments that span a substantial portion of the container's length. The containers may be in forms such as tubes or sheaths and include openings to allow nerve cell entry and exit, supporting the guided, oriented, and supported regrowth of nerve cells.
The problem being solved stems from the challenges associated with repairing severed or damaged nerve cells, particularly over critical gap lengths where natural regeneration is inefficient. Existing treatments like autografts have limitations including donor site morbidity, limited availability, and functional mismatches, while conventional nerve conduits lack the internal structure and environment conducive to effective nerve regrowth. The invention addresses these challenges by providing a flexible, permeable nerve conduit with internal silk-based fiber elements and optimized physical and biochemical properties to enhance axonal regeneration, guide cellular orientation, prevent scar tissue infiltration, and support functional nerve recovery.
Claims Coverage
The claims cover multiple inventive features related to a medical device structured as a flexible nerve regeneration conduit incorporating a silk-based sheath and internal silk fiber elements with hydrophilic coatings, controlled porosity, and biochemical gradients.
Flexible nerve sheath with silk-based construction
A nerve conduit sheath that is at least partly flexible, achieved by crosslinking, capable of bending into less than about a 90° angle without breaking or kinking while maintaining luminal patency, and comprising silk.
Permeable sheath supporting nerve cell ingress and egress
The sheath is configured with openings, including a plurality of pores up to about 200 μm, allowing at least partial influx of nutrients and outflow of waste. The sheath allows nerve cells to enter and exit through entrance and exit points.
Interior element comprising silk fibers or filaments spanning the sheath length
Within the interior of the sheath, at least one element comprising fibers or filaments spans at least a portion and preferably a majority of the sheath length, facilitating nerve cell regrowth guidance.
Hydrophilic coating of silk elements and bundles
Individual silk elements are wrapped in a first hydrophilic coating, bundles of silk elements are wrapped in a second hydrophilic coating, with hyaluronic acid used as a preferred coating material, promoting handling and stability.
Controlled porosity and distribution of pores
The sheath’s pore distribution can be uniform or non-uniform along its length, designed to prevent cell entry while allowing nutrient diffusion and minimizing scar tissue infiltration.
Incorporation of biochemical gradients and additional constituents
The conduit may comprise gradients of growth factors, microtubules, actin filaments, neurofilaments, cells, or cytokine inhibitors distributed to promote axonal growth and nerve regeneration.
Manufacturing methods involving freeze-gel-freeze-dry-crystallize processes
Methods include freezing silk protein solutions in molds, contacting with gelling agents such as PEG and acetic acid to create porous, flexible conduits, freeze drying to maintain pore structure, and crystallization to enhance mechanical strength.
Use of silk types including fibroin and spidroin from mulberry and non-mulberry silkworms and spiders
Silk fibers from Bombyx mori, Nephila species, and recombinant or analog silk proteins are used for conduit construction and internal fiber elements.
The patent claims cover a medical device comprising a flexible, porous, silk-based sheath with interior silk fiber elements that are hydrophilically coated and spatially organized to encourage and guide nerve cell regrowth. It includes specific structural features such as pore size and distribution, biochemical gradients, and defined manufacturing methods to fabricate conduits for nerve repair with improved functional outcomes.
Stated Advantages
The device combines flexibility with sufficient mechanical strength to avoid breaking or kinking during handling or implantation.
The conduit design permits nutrient influx and waste removal while preventing scar tissue infiltration, improving a conducive environment for nerve regeneration.
Hydrophilic coatings on silk fibers enhance handling, stability, and maintain spacing between fiber bundles to support nerve cell migration.
The device can be manufactured with controlled porosity and configured with biochemical gradients to enhance axonal growth and guidance.
The medical device facilitates nerve regeneration over large gap lengths (up to about 20 cm), surpassing limitations of current autografts and nerve conduits.
Improved surgeon handling due to the device’s physical properties, including the ability to cut to bespoke lengths and maintain shape during implantation.
Documented Applications
Treatment of severed or injured nerve cells, including peripheral nerves and spinal cord nerve tracts.
Bridging nerve gaps ranging from about 1 cm up to about 20 cm to facilitate regrowth and reconnection of nerves.
Use in both human and veterinary medicine to restore functional control, sensation, and movement in limbs affected by nerve injury.
Implantation in spaces previously occupied by a nerve cell, especially in conditions where the nerve cell has been partially or completely severed.
Application in nerve repair procedures requiring the guidance and support of axonal regeneration to restore function after trauma or disease-induced degeneration.
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