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It takes some nerve: How biologics and fibres can advance nerve generation

If pharmaceuticals and biologics could be successfully loaded into fibres, it could make for an entirely new approach to nerve regeneration, as well as advanced drug delivery and tissue engineering. Dr. Kevin Nelson, founder and CSO, TissueGen explains.

Traditional melt extrusion processes used to manufacture fibres destroys the viability of most drugs and biologics, given that melt extrusion must occur at temperatures often exceeding 200 degrees celsius.

Today, emerging technologies such as electrospinning and wet-extrusion processes occur at room temperature, greatly expanding the range of pharmaceuticals and biologics that can be incorporated into implantable medical devices and therapies. These low temperature processes potentially allow a broader variety of drugs and biologics to be loaded into fibres compared to melt extrusion; however, this benefit comes at a price. In these low temperature processes solvent exposure is accepted in exchange for heat exposure. 

During the wet spinning process, a polymer is dissolved in a solvent, and this solution is injected under pressure through a spinneret into a coagulating bath. The coagulating bath is comprised of a solution that is highly miscible with the solvent used to dissolve the polymer, yet is a non-solvent for the polymer. As the polymer solution stream enters the coagulating bath, the solvent diffuses from the polymer solution stream into the coagulating bath, locally increasing the polymer concentration. At the same time, the polymer stream is exposed to the non-solvent of the coagulation bath. This combined effect causes the polymer molecules to precipitate out of the solution, forming a solid fibre. The polymer fibre is then pulled from the coagulation bath and taken through several draw stations where the fibre is stretched and heated, but at typically much lower temperatures than possible with melt extrusion because the residual solvents (and non-solvents from the coagulating bath), rather than heat, provide the molecular mobility required to allow the polymer chains to align and create entanglement sites that provide high mechanical properties to the fibre.

Providers of these low temperature processes must now create a means whereby the drugs are protected from the frequently harsh solvents associated with electrospinning or wet extrusion.  These protection processes now become the heart of the intellectual property of these manufacturers. When successful, the biological activity of incorporated sensitive growth factors and biologically-based agents can now be preserved so that a wide range of pharmaceuticals and biologics remain viable when loaded to biodegradable fibre. These electrospun or wet-extruded fibres are ideal for use in current and next-generation implantable medical devices, regenerative medicine, and as pharmaceutical depots for slow controlled release. The localised pharmaceutical delivery capability of these fibres may even allow medical device designers to locally alter the body’s response to the device.

The controlled release of wet extruded fibre-based systems is well-suited for a variety of medical applications, including meshes and weaves for current textile applications, sutures, ligatures and scaffolding. The fibres are also strong enough to potentially be used to create biodegradable, self-expanding, pharmaceutical-loaded cardiovascular stents. 

Using this proprietary technology, even viral particles have been successfully loaded into fibres, implanted into immune compromised animals, and have shown extremely efficient transfection.

With wet extrusion, sensitive growth factors such as Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF), and other sensitive biological molecules including immune proteins and enzymes such as IgG and even live adenoviruses can be loaded and delivered via fibres. 

Fibres loaded with such biologics and incorporated into implantable medical devices may find use in several regenerative applications, including:

One specific example of how this technology may be applied is the repair of the nervous system. During embryonic development, growing nerves are known to follow growth factor concentration gradients; and this also true in wound-healing for adults. Therefore, it is speculated that if it were possible to create a concentration gradient of the right growth factors in an adult wound-healing situation that it may be possible to induce accelerated, focused regeneration of axons. Using these same growth factors loaded into a fibre, it may be possible to create a conduit containing a variable-pitched, growth factor-loaded coil, meaning the loops of the coil are much closer together at one end than the other. This gives an opportunity to create a concentration gradient moving down the center of the coil as there will be more growth factor where the loops are closer, and less growth factor where they are further apart. This drug-loaded fibre-based coil may then be a key component to creating nerve regeneration across long gaps in humans.

This technology may also prove beneficial to other areas of nerve repair both in the peripheral and central nervous systems.

By preforming extrusion at or near room temperature, the limitations to drug viability that have impeded how pharmaceuticals and biologics can be delivered via implantable medical textiles can finally be overcome. 

Extrusion processes that occur at room temperature enable loading a wide range of pharmaceutical and biological agents into biodegradable implantable devices thereby enabling localized delivery within the body which may facilitate breakthroughs in medical applications such as nerve generation, spinal cords injury repair, tissue engineering and even vascular grafts.

This technology has the potential to be particularly well-suited for the repair of the nervous system, as nerve cells are known to follow growth factor concentration gradients during development and after injury.

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