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Biodegradable polyesters blended with crab shells unveil effective nerve repair material

Researchers at the University of Washington (UW) recently announced a significant innovation in nerve repair material. They have developed a new hybrid fiber by weaving industrial polyester and chitosan which has shown huge promise for creating tiny tubes (called nerve guides) that support repair of a severed nerve. The first component of the new material-polycaprolactone, is a strong, flexible, biodegradable polyester commonly used in sutures. The second component, chitosan, is found in the shells of crustaceans like crabs and shrimps. The hybrid fiber combines the biologically favorable qualities of the natural material with the mechanical strength of the synthetic polymer. Miqin Zhang, a UW professor of material science and engineering says, "A nerve guide requires very strict conditions. It needs to be biocompatible, stable in solution, resistant to collapse and also pliable, so that surgeons can suture it to the nerve." On its own, polycaprolactone is not suitable for use as a nerve guide because water-based cells don't like to grow on the polyester's water-repelling surface. On the other hand, chitosan is cheap, readily available, biodegradable and biocompatible. Chitosan has a rough surface similar to the surfaces found inside the body that cells can attach to. However, chitosan swells in water, making it weak in wet environments. As a result, the researchers developed a thread made of crab shell and polyester to repair broken nerves.
After an injury that severs a peripheral nerve, such as one in a finger, nerve endings continue to grow. But to regain control of the nerve surgeons must join the two fragments. For large gaps surgeons used to attempt a more difficult nerve graft. Current surgical practice is to attach tiny tubes, called nerve guides, that channel the two fragments toward each other. Currently, commercial nerve guides are made from collagen, a structural protein derived from animal cells. But collagen is expensive, the protein tends to trigger an immune response and the material is weak in wet environments, such as those inside the body. The strength of the nerve guide is important for budding nerve cells. As an alternative to collagen nerve guides, the team combined the industrial polyester polycaprolactone with chitosan at the nanometer scale by first using a technique called electrospinning to draw the materials into nanometer-scale fibers, and then weaving the fibers together. The study notes resulting material to have a texture similar to that of the nanosized fibers of the connective tissue that surrounds human cells. The researchers maintain that the two materials are different and are difficult to blend, but proper mixing is crucial because imperfectly blended fibers have weak points. As a part of the study, the team tested a guide made from the chitosan-polyester blend against another biomaterial under study, polylacticcoglycolic acid, and a commercially available collagen guide. The chitosan-polyester nerve guide showed the most consistent performance for strength, flexibility and resistance to compression under both dry and wet conditions. Under wet conditions, which the researchers say best mimics those in the body, the chitosan-polyester blend required twice as much force to push the tube halfway shut as the other biomaterial, and eight times as much force as the collagen tube. In addition to developing strong nerve guides for repairs, the new chitosan-polyester blend is also envisaged to work well for wound dressings, heart grafts, tendons, ligament, cartilage, muscle repair and other biomedical applications.

Researchers at Purdue University have developed a technique using spun-sugar filaments to create a scaffold of tiny synthetic tubes that might serve as conduits to regenerate nerves severed in accidents or blood vessels damaged by disease. The sugar filaments are coated with a corn-based degradable polymer, and then the sugar is dissolved in water, leaving behind bundles of hollow polymer tubes that mimic those found in nerves. The scaffold could be used to promote nerve regeneration by acting as a bridge placed between the ends of severed nerves. The researchers are initially concentrating on the peripheral nerves found in the limbs and throughout the body because nerve regeneration is more complex in the spinal cord. About 800,000 peripheral nerve injuries are reported annually in the United States, with about 50,000 requiring surgery. The approach also might have applications in repairing blood vessels damaged by trauma and disease such as atherosclerosis and diabetes. The new approach represents a potential alternative to the conventional surgical treatment, which uses a nerve "autograft" taken from the leg or other part of the body to repair the injured nerves. Researchers are trying to develop artificial scaffolds to replace the autografts because removing the donor nerve causes a lack of sensation in the portion of the body where it was removed. The autograft is the lesser of two evils because you have to sacrifice a healthy nerve to repair a damaged segment.
Researchers from Cornell University published similar findings that focused on using the technique to create vascular networks for providing blood and nutrients to tissues and grafts. The synthetic scaffold resembles the structural assembly of natural nerves, which are made of thousands of small tubes bundled together. These tubes act as sheaths that house the conducting elements of the nerve cell. The first step in making the tubes is to spin sugar fibers from melted sucrose. The sugar filaments were coated with a polymer called poly L-lactic acid. After the filaments were dissolved, hollow tubes of the polymer remained. The researchers then grew nerve-insulating cells called Schwann cells on these polymer tubes. These cells automatically aligned lengthwise along the tubes, as did nerve cells grown on top of the Schwann cells. This alignment is critical for the fast growth of nerves. Nerve cells grew not only inside the hollow tubes but also around the outside of the tubes. This finding is important because the increased surface area may accelerate the regeneration process following an accident. The scaffolds are designed specifically to regenerate a portion of a nerve cell called the axon, a long fiber attached to the cell body that transmits signals. Fast regeneration is essential to prevent the atrophy of muscles and organs connected to severed nerves. The researchers also discovered that the polymer tubes contain pores that are ideal for supplying nutrients to growing nerve cells and removing waste products from the cells. Images of the polymer-coated sugar strands were taken using a scanning electron microscope. Another instrument, called an atomic force microscope, was used to obtain images of the hollow tubes and pores in the walls of the tubules. Other images using fluorescent dyes revealed the nerve cell alignment along the tubes. The work was done using cell cultures in petri dishes, but ongoing work focuses on implanting the scaffolds in animals. The method for creating the scaffolds is relatively simple and inexpensive and does not require elaborate laboratory equipment. A provisional patent application on the material has been filed.
Cotton candy and networks of veins and capillaries inside living tissue, at first glance, may not have much in common. Dr. Leon Bellan, a former doctoral student at Cornell University's Nanobiotechnology Center and Dr. Jason Spector of New York-Presbyterian Hospital/Weill Cornell Medical Center, thought otherwise. Using cotton candy, the team developed a promising new method to create artificial vascular and capillary systems for laboratory-grown tissue, skin, muscle or fat. The three-dimensional vascular network was created by pouring a liquid polymer over a ball of cotton candy attached to two sugar rods. After the polymer solidified, the sugar is dissolved, leaving a complex network of tiny channels. To test how well blood could flow through the artificial vascular system, the researchers injected ratís blood containing fluorescent dye. By following its progress through the network using a video fluorescence microscope, they confirmed that the microchannels and the other larger channels were observed to fill with blood. This technique could someday solve a central problem of developing artificial organs, currently limited by the difficulty of reconstructing the human bodyís complex and essential circulatory system quickly and cheaply. Without fine-grained nets of capillaries that can be connected to the body's circulatory system, complex tissue can't dispose of waste effectively, nor receive the nutrients it needs from blood cells. While future medical applications are compelling, putting this technique into use in reconstructive surgery and wound healing treatments will likely require significantly more research and extensive testing.
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