distortion, which narrows the tubular lumen and can impede regeneration. it is advantageous that the degradation time of pgs can be varied by changing the degree of crosslinking and the ratio of sebacic acid to glycerol. in a study by sundback et al. (2005), implanted pgs and plga conduits had similar early tissue responses; however, plga inflammatory responses spiked later, while pgs inflammatory responses continued to decreases. polyethylene glycol hydrogel polyethylene glycol (peg) hydrogels are biocompatible and proven to be tolerated in many tissue types, including the cns. mahoney and anseth formed peg hydrogels by photopolymerizing methacrylate groups covalently linked to degradable peg macromers. hydrogel degradation was monitored over time by measuring mechanical strength (compressive modulus) and average mesh size from swelling ratio data. initially, the polymer chains were highly cross-linked, but as degradation proceeded, ester bonds were hydrolyzed, allowing the gel to swell; the compressive modulus decreased as the mesh size increased until the hydrogel was completely dissolved. it was demonstrated that neural precursor cells were able to be photoencapsulated and cultured on the peg gels with minimal cell death. because the mesh size is initially small, the hydrogel blocks inflammatory and other inhibitory signals from surrounding tissue. as the mesh size increases, the hydrogel is able to serve as a scaffold for axon regeneration. biological polymers there are advantages to using biological polymers over synthetic polymers. they are very likely to have good biocompatibility and be easily degraded, because they are already present in nature in some form. however, there are also several disadvantages. they have unwieldy mechanical properties and degradation rates that cannot be controlled over a wide range. in addition, there is always the possibility that naturally-derived materials may cause an immune response or contain microbes. in the production of naturally-derived materials there will also be batch-to-batch variation in large-scale isolation procedures that cannot be controlled. some other problems plaguing natural polymers are their inability to support growth across long lesion gaps due to the possibility of collapse, scar formation, and early re-absorption. despite all these disadvantages, some of which can be overcome, biological polymers still prove to be the optimal choice in many situations. polysialic acid (psa) polysialic acid (psa) is a relatively new biocompatible and bioresorbable material for artificial nerve conduits. it is a homopolymer of α2,8-linked sialic acid residues and a dynamically regulated posttranslational modification of the neural cell adhesion molecule (ncam). recent studies have demonstrated that polysialylated ncam (polysia-ncam) promotes regeneration in the motor system. psa shows stability under cell culture conditions and allows for induced degradation by enzymes. it has also been discovered recently that psa is involved in steering processes like neuritogenesis, axonal path finding, and neuroblast migration. animals with psa genetically knocked out express a lethal phenotype, which has unsuccessful path finding; nerves connecting the two brain hemispheres were aberrant or missing. thus psa is vital for proper nervous system development. collagen type i/iii collagen is the major component of the extracellular matrix and has been widely used in nerve regeneration and repair. due to its smooth microgeometry and permeability, collagen gels are able to allow diffusion of molecules through them. collagen resorption rates are able to be controlled by crosslinking collagen with polypoxy compounds. additionally, collagen type i/iii scaffolds have demonstrated good biocompatibility and are able to promote schwann cell proliferation. however, collagen conduits filled with schwann cells used to bridge nerve gaps in rats have shown surprisingly unsuccessful nerve regeneration compared to nerve autografts. this is because biocompatibility is not the only factor necessary for successful nerve regeneration; other parameters such as inner diameter, inner microtopography, porosity, wall thickness, and schwann cell seeding density will need to be examined in future studies in order to improve the results obtained by these collagen i/iii gels. spider silk fiber spider silk fibers are shown to promote cellular adhesion, proliferation, and vitality. allmeling, jokuszies et al. showed that schwann cells attach quickly and firmly to the silk fibers, growing in a bipolar shape; proliferation and survival rates were normal on the silk fibers. they used spider silk fibers to create a nerve conduit with schwann cells and acellularized xenogenic veins. the schwann cells formed columns along the silk fibers in a short amount of time, and the columns were similar to bands of bungner that grow in vivo after pns injury. spider silk has not been used in tissue engineering until now because of the predatory nature of spiders and the low yield of silk from individual spiders. it has been discovered that the species nephila clavipes produces silk that is less immunogenic than silkworm silk; it has a tensile strength of 4 x 109 n/m, which is six times the breaking strength of steel. because spider silk is proteolytically degraded, there is not a shift in ph from the physiological ph during degradation. other advantages of spider silk include its resistance to fungal and bacterial decomposition for weeks and the fact that it does not swell. also, the silk's structure promotes cell adhesion and migration. however, silk harvest is still a tedious task and the exact composition varies among species and even among individuals of the same species depending on diet and environment. there have been attempts to synthetically manufacture spider silk. further studies are needed to test the feasibility of using a spider silk nerve conduit in vitro and in vivo. silkworm silk fibroin in addition to spiders, silkworms are another source of silk. protein from bombyx mori silkworms is a core of fibroin protein surrounded by sericin, which is a family of glue-like proteins. fibroin has been characterized as a heavy chain with a repeated hydrophobic and crystallizable sequence: gly-ala-gly-ala-gly-x (x stands for ser or tyr). the surrounding sericin is more hydrophilic due to many polar residues, but it does still have some hydrophobic β-sheet portions. silks have been long been used as sutures due to their high mechanical strength and flexibility as well as permeability to water and oxygen. in addition, silk fibroin can be easily manipulated and sterilized. however, silk use halted when undesirable immunological reactions were reported. recently, it has been discovered that the cause of the immunological problems lies solely with the surrounding sericin. since this discovery, silk with the sericin removed has been used in many pharmaceutical and biomedical applications. because it is necessary to remove the sericin from around the fibroin before the silk can be used, an efficient procedure needs to be developed for its removal, which is known as degumming. one degumming method uses boiling aqueous na2co3 solution, which removes the sericin without damaging the fibroin. yang, chen et al. demonstrated that the silk fibroin and silk fibroin extract fluid show good biocompatibility with schwann cells, with no cytotoxic effects on proliferation. chitosan chitosan and chitin belong to a family of biopolymers composed of β(1–4)-linked n-acetyl-d-glucosamine and d-glucosamine subunits. chitosan is formed by alkaline n-deacetylation of chitin, which is the second most abundant natural polymer after cellulose. chitosan is a biodegradable polysaccharide that has been useful in many biomedical applications such as a chelating agent, drug carrier, membrane, and water treatment additive. chitosan is soluble in dilute aqueous solutions, but precipitates into a gel at a neutral ph. it does not support neural cell attachment and proliferation well, but can be enhanced by ecm-derived peptide attachment. chitosan also contains weak mechanical properties, which are more challenging to overcome. degree of acetylation (da) for soluble chitosan ranges from 0% to 60%, depending on processing conditions. a study was conducted to characterize how varying da affects the properties of chitosan. varying da was obtained using acetic anhydride or alkaline hydrolysis. it was found that decreasing acetylation created an increase in compressive strength. biodegradation was examined by use of lysozyme, which is known to be mainly responsible for degrading chitosan in vivo by hydrolyzing its glycosidic bonds and is released by phagocytic cells after nerve injury. the results reveal that there was an accelerated mass loss with intermediate das, compared with high and low das over the time period studied. when drg cells were grown on the n-acetylated chitosan, cell viability decreased with increasing da. also, chitosan has an increasing charge density with decreasing da, which is responsible for greater cell adhesion. thus, controlling the da of chitosan is important for regulating the degradation time. this knowledge could help in the development of a nerve guidance conduit from chitosan. aragonite aragonite scaffolds have recently been shown to support the growth of neurons from rat hippocampi. shany et al. (2006) proved that aragonite matrices can support the growth of astrocytic networks in vitro and in vivo. thus, aragonite scaffolds may be useful for nerve tissue repair and regeneration. it is hypothesized that aragonite-derived ca2+ is essential for promoting cell adherence and cell–cell contact. this is probably carried out through the help of ca2+-dependent adhesion molecules such as cadherins. aragonite crystalline matrices have many advantages over hydrogels. they have larger pores, which allows for better cell growth, and the material is bioactive as a result of releasing ca2+, which promotes cell adhesion and survival. in addition, the aragonite matrices have higher mechanical strength than hydrogels, allowing them to withstand more pressure when pressed into an injured tissue. alginate alginate is a polysaccharide that readily forms chains; it can be cross-linked at its carboxylic groups with multivalent cations such as cu2+, ca2+, or al3+ to form a more mechanically stable hydrogel. calcium alginates form polymers that are both biocompatible and non-immunogenic and have been used in tissue engineering applications. however, they are unable to support longitudinally oriented growth, which is necessary for reconnection of the proximal end with its target. in order to overcome this problem, anisotropic capillary hydrogels (ach) have been developed. they are created by superimposing aqueous solutions of sodium alginate with aqueous solutions of multivalent cations in layers. after formation, the electrolyte ions diffuse into the polymer solution layers, and a dissipative convective process causes the ions to precipitate, creating capillaries. the dissipative convective process results the opposition of diffusion gradients and friction between the polyelectrolyte chains. the capillary walls are lined with the precipitated metal alginate, while the lumen is filled with the extruded water. prang et al. (2006) assessed the capacity of ach gels to promote directed axonal regrowth in the injured mammalian cns. the multivalent ions used to create the alginate-based ach gels were copper ions, whose diffusion into the sodium alginate layers created hexagonally structured anisotropic capillary gels. after precipitation, the entire gel was traversed by longitudinally oriented capillaries. the ach scaffolds promoted adult npc survival and highly oriented axon regeneration. this is the first instance of using alginates to produce anisotropic structured capillary gels. future studies are need to study the long-term physical stability of the ach scaffolds, because cns axon regeneration can take many months; however, in addition to being able to provide long-term support the scaffolds must also be degradable. of all the biological and synthetic biopolymers investigated by prang et al. (2006), only agarose-based gels were able to compare with the linear regeneration caused by ach scaffolds. future studies will also need to investigate whether the ach scaffolds allow for reinnervation of the target in vivo after a spinal cord injury. hyaluronic acid hydrogel hyaluronic acid (ha) is a widely used biomaterial as a result of its excellent biocompatibility and its physiologic function diversity. it is abundant in the extracellular matrix (ecm) where it binds large glycosaminoglycans (gags) and proteoglycans through specific ha-protein interactions. ha also binds cell surface receptors such as cd44, which results in the activation of intracellular signaling cascades that regulate cell adhesion and motility and promote proliferation and differentiation. ha is also known to support angiogenesis because its degradation products stimulate endothelial cell proliferation and migration. thus, ha plays a pivotal role in maintaining the normal processes necessary for tissue survival. unmodified ha has been used in clinical applications such as ocular surgery, wound healing, and plastic surgery. ha can be crosslinked to form hydrogels. ha hydrogels that were either unmodified or modified with laminin were implanted into an adult central nervous system lesion and tested for their ability to induce neural tissue formation in a study by hou et al.. they demonstrated the ability to support cell ingrowth and angiogenesis, in addition to inhibiting glial scar formation.