Spider Silk Applications in Nerve Regeneration

Golden orb weaver (Nephila edulis) collected in Australia. Image Credit: Gail Hampshire (2014)

Overview

Researchers have shown interest in spider silk due to its potential in medical applications. Spider silk is biocompatible, strong, and has antimicrobial properties. These traits allow spider silk to be used in different medical situations such as tissue engineering, sutures, and in many studies spider silk has proven to serve as a promising material for nerve regeneration.

Definitions

In vivo: within the organism; In vitro: outside the organism
Proliferation: division and multiplication of cells
Schwann Cells: cells in the peripheral nervous system responsible for the growth and maintenance of the myelin sheath around neuronal axons
Spidroins: building blocks of spider silk
Spinnerets: spider silk producing glands

Spider silk bandage

Image Credit: SynBioBeta (2024)

Past Applications of Spider Silk

In ancient Rome and Greece it was common to use spider webs as a form of bandaging for wounds

Doctors believed that the silk used to make the webs had natural remedies to protect against infection and heal wounds

Became an impractical solution to treating wounds because of how difficult it is to collect spider silk in large quantities and the lack of proven effectiveness compared to modern treatments. [7]

Types of Spider Silk Produced by Orb Weaving Spiders

Major Ampullate (MA) Silk

Has high tensile strength and elasticity
Typically used to build an outline of the spiders web
Can be used as a lifeline to escape from predators [8]

Minor Ampullate (Mi) Silk

Used to reinforce the web
Creates the initial spiral to build the web from [8]

Flagelliform (Flag) Silk

Primary silk used to capture prey
Has one of the highest levels of elasticity to ensure prey get caught in the web
Can also be used to help collect water [8]

Aggregate Silk

What makes the silk sticky to help capture and keep prey within their web
Spiders form of "glue" [8]

Silk glands dissected from a false black widow, still attached to their spinneret

Image Credit: Ayoub (2017)

Major Ampullate Silk

With the combination of strength and extensibility, MA silk outperforms any synthetic equivalents. These traits make this silk one of the world's toughest natural material.

MA Silk is primarily composed of major ampullate spidroins (MaSps). MaSp1 and MaSp2 contribute to the strength and elasticity of the MA silk fiber.

This silk has proven to be a suitable material to promote regeneration after long-distance nerve defects. [3]

Figure 1: Strain and Stress Test of Various Fiber Materials: Strain refers to the elasticity of a fiber, so how long can it be stretched before snapping. Stress refers to the rigidity of a fiber, so how much power it can endure before losing its composition.

Spider Silk Engineering Properties

In Figure 2, spider silk has a balance in both engineering applications of elasticity and rigidity. It can be stretched to extreme lengths while also maintaining its composition which is not commonly seen especially within natural compounds.

Kevlar is known for its strength in helping stop bullets and stab wounds, but lacks stretchability. However, in spider silk we can see that it can reach similar highs of stress to the Kevlar once it reaches a certain elastic length.

This highlight the importance of understanding spider silk for use in biomedical applications as it has such diverse strengths and traits. [9]

Nerve Regeneration Applications of Spider Silk

Why Spider Silk?

Spider silk promotes cell regeneration at a faster rate than other materials, due to its mechanical strength it is able to be used in long gap nerve defect regeneration. Its antibacterial and anti-inflammatory properties allow it to last longer and not trigger a immune response in the host.

Example of a conduit which can be used with spider silk

Image Credit: Semmler, Lorenz, et al. (2023)

Artificial Conduits

Alternative form of treatment for nerve regeneration that does not require immunosuppressants. Spider silk is used to form the inside of a tube structure which bridges the gaps between nerves guiding the growth of nerve fibers across the gap. [1]

Figure 2: Comparison of the growth of rSCs, rFBs and rDRG neurons on different substrates. Success shown on spider silk. [4]

Meshwork

Dragline silk is harvested and arranged in a crisscross pattern around 1x1 cm metal frames of stainless steel. These meshworks were used to seed many different kinds of neurons. Cultivating cells and assessing their behaviors such as proliferation and migration in vitro. [4]

Figure 3: Reconstructed arm with spider silk nerve graft: Patient was in a car accident with open fractures in both forearms. Forearm was reconstructed with skin taken from his thigh. Nerve graft inserted to help restore functionality of moving his arm. [1]

Figure 4: Regeneration of nerve cells in the spider silk nerve implants: Shows advance growth over 4, 5, and 6 months, with cells clustering and organizing into clearer structure. Schwann cells are stained anti-S-100 in red. Nerve fibers are stained anti-neurofilament in green. Cell nuclei appear blue in DAPI. [6]

Spider Silk as an Artificial Conduit

In a clinical study involving four patients with different severe nerve damage, spider silk filled vein grafts were used to restore partial muscle function. In figure 3, one of the patients went from total muscle function loss to being able to make a fist and moving his fingers. Similar results were found in the other patients proving spider silk to be a new possible form of treatment in nerve reconstruction, although not restoring complete functionality. [1]

In another study, researchers used recombinant spider silk to build nerve guidance conduits (NGC). Their results showed that when the NGCs were filled with collagen fibers, nerve function was effectively restored. Nerves were able to build networks off each other, and fire action potentials used to communicate with other cells. In figure 4 it demonstrates how the conduits support the organizations of nerve cells with it promoting growth in the nerve defects, increasing over certain time periods. [6] Although this research has not yet been applied in a clinical study, it shows promise as a form of treatment for peripheral nerve repair. [2]

Figure 5: Spider silk weaved around metal frame. [5]

Figure 6: Neurons formed along spider silk mesh creating structures in the culture. [5]

Spider Silk in a Mesh Frame

One method of understanding more about nerve regeneration is analyzing cells from outside an organism, otherwise known as in vitro. In recent years scientists have developed spider silk mesh work in which spider silk is weaved around a 1x1 cm stainless steel frame in order to create arrays which can be used in cell culture experiments. [4]

These meshworks which use harvested dragline silk create a network in which cells can easily attach too creating a seed for proliferation in which you can observe the specific behaviors of certain nerve cell. One such experiment compares the growth of rat schwann cells (rSCs), rFBs, rDRG on silk versus controls, with the silk being favored for both growth and migration alignment proving silk being better over other materials. With spider silk encouraging the nerve cells to preform and grow as they normally would. [4]

Approaches done for the first time have shown that these new techniques could make the method of testing how cells interact before being implanted more efficient. [5]

Future Outlook

Spider silk shows a lot of promise for the regeneration of nerves with the ability to restore function in peripheral nerves and correct nerve defects formed by lesions from trauma or oncological reasons. However much of research that goes into it is relatively new and needs time to work out possible flaws and be used in other research fields.

From Our Own Backyard

Orb weaver (Araneidae family) collected by Nadja Bloetner on UMBC campus

Image Credit: Eli Gooding

Orb weaver using dragline silk to drop and pull itself back up

Video Credit: Eli Gooding

Fun Facts About Spider Silk

Click on the images to learn captivating facts about spider silk!

Spiders go fishing

There are some inventive ways spiders capture prey. Bolas spiders place a sticky drop of silk at the end of a silken line (a bolas), swinging it much like a fishing line to catch moths. [15]

Image Credit: Matt Coors (2009)

Real life Spiderman

A strand of spider silk if pencil thick could stop a Boeing 457 flight mid- air and could theoretically stop a runaway train. [13]

Image Credit: Brian Reiter

Spiders recycle silk

After about a day webs lose stickiness due to factors like dust accumulation and exposure to air. To save energy, spiders eat their web before forming a new one, allowing silk threads to be digested into protein, collected in silk glands, and recycled. [14]

Image Credit: Kalpana Mishra

Myth vs. Fact

What you think you know about spiders is false! Click on the images to debunk common spider myths

Myth: Spider bites are often deadly

In the U.S. only two kinds of spiders possess venom that could harm humans (black widows and brown recluses) and neither are aggressive.

In fact, most people will never be bitten by a spider in their lifetime because spiders are not interested in interacting with humans. [10]

Image Credit: Drive-by Exterminators

Myth: All spiders spin webs

A web is a silk structure a spider makes to catch prey. Only about half of known spider species catch prey using webs. Other species actively hunt for prey or sit and wait for prey to come to them. [11]

Image Credit: Tone Killick

Myth: Harvesters are the most venomous spiders in the world, but their fangs are just too small to bite humans

Harvesters are not spiders (they are arachnids), nor do they have venom glands or fangs, which render them harmless. [12]

Image Credit: Dr. Morley Read

By: Nadja Bloetner, Eli Gooding, Ethan Chen, and Geneva Mon

Sources

Vogt, P., Radtke, C., Krezdorn, N., Kollewe, K., Liebsch, C., Dastagir, K. & Strauß, S. (2024). Biological conduits based on spider silk for reconstruction of extended nerve defects. Innovative Surgical Sciences, 9(3), 133-142. https://doi.org/10.1515/iss-2023-0050.
Pawar, K., Welzel, G., Haynl, C., Schuster, S., & Scheibel, T. (2019). Recombinant Spider Silk and Collagen-Based Nerve Guidance Conduits Support Neuronal Cell Differentiation and Functionality in Vitro. ACS Applied Bio Materials, 2(11), 4872–4880. https://doi.org/10.1021/acsabm.9b00628.
Branković, M., Zivic, F., Grujovic, N., Stojadinovic, I., Milenkovic, S., & Kotorcevic, N. (2024). Review of Spider Silk Applications in Biomedical and Tissue Engineering. Biomimetics, 9(3), 169. https://doi.org/10.3390/biomimetics9030169
Millesi F, Weiss T, Mann A, et al. Defining the regenerative effects of native spider silk fibers on primary Schwann cells, sensory neurons, and nerve-associated fibroblasts. The FASEB Journal. 2021; 35:e21196. https://doi.org/10.1096/fj.202001447R.
Roloff, Frank, Strauß, Sarah, Vogt, Peter M., Bicker, Gerd, Radtke, Christine, Spider Silk as Guiding Biomaterial for Human Model Neurons, BioMed Research International, 2014, 906819, 7 pages, 2014. https://doi.org/10.1155/2014/906819.
Kornfeld, T., Nessler, J., Helmer, C., Hannemann, R., Waldmann, K. H., Peck, C. T., Hoffmann, P., Brandes, G., Vogt, P. M., & Radtke, C. (2021). Spider silk nerve graft promotes axonal regeneration on long distance nerve defect in a sheep model. Biomaterials, 271, 120692. https://www.sciencedirect.com/science/article/abs/pii/S0142961221000430
Loredo Hand Care Institute. (2019). Loredohands.com. https://www.loredohands.com/blog/924351-bandages/.
Eisoldt, L., Smith, A., & Scheibel, T. (2011). Decoding the secrets of spider silk. Materials Today, 14(3), 80–86. https://doi.org/10.1016/s1369-7021(11)70057-8.
Ko, F. K., Kawabata, S., Inoue, M., Niwa, M., Fossey, S., & Song, J. W. (2001). Engineering Properties of Spider Silk. MRS Proceedings, 702. https://doi.org/10.1557/proc-702-u1.4.1.
6 Common Spider Myths, Debunked. (2024, October 9). Right as Rain by UW Medicine; RightAsRain. https://rightasrain.uwmedicine.org/well/health/spider-bite-myths.
Myth: All spiders make webs. (n.d.). Burke Museum. https://www.burkemuseum.org/collections-and-research/biology/arachnology-and-entomology/spider-myths/myth-all-spiders-make-webs.
Eaton, E. R. (2015, November 12). Daddy Longlegs in Myth and Legend. After Bite Insectlopedia. https://insectlopedia.com/daddy-longlegs-in-myth-and-legend/.
Powers, A. (2013). Spider Silk: Sronger than Steel? Nature’s Supermaterial. Berkeley Scientific Journal, 18(1). https://doi.org/10.5070/bs3181020651.
Spider Silk. (n.d.). Www.chm.bris.ac.uk. https://www.chm.bris.ac.uk/motm/spider/page2.htm.
Eight strange but true spider facts. (n.d.). Smithsonian Institution. https://www.si.edu/stories/eight-strange-true-spider-facts.

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