In traumatic brain injury (TBI), a series of damaging events is initiated that lead to cell death and overall dysfunction, which cause the formation of an irregularly-shaped lesion cavity.
[8] It is also very important for minimally invasive delivery that the MC solution has a viscosity at temperatures below its LCST, which allows it to be injected through a small gauge needle for implantation in in vivo applications.
Due to these disadvantages, use of MC in neural tissue regeneration requires attaching a biologically active group onto the polymer backbone in order to enhance cell adhesion.
[9] Longitudinally oriented channels are macroscopic structures that can be added to a conduit in order to give the regenerating axons a well-defined guide for growing straight along the scaffold.
A molding technique was created by Wang et al. for forming a nerve guidance conduit with a multi-channel inner matrix and an outer tube wall from chitosan.
[10] In their 2006 study, Wang et al. threaded acupuncture needles through a hollow chitosan tube, where they are held in place by fixing, on either end, patches created using CAD.
[17] Examination by scanning electron microscope and TEM showed no signs of axon thinning due to stretch, and the cytoskeleton appeared to be normal and intact.
[18] The mechanical shearing was created by dragging out a 0.2 ml bolus to 3 cm with forceps; fibronectin aggregates into insoluble fibers at the rapidly moving interface in an ultrafiltration cell.
[20] In the past decade, scientists have also developed numerous methods for production of aligned nanofiber scaffolds, which serve to provide additional topographic cues to cells.
[7] In a study conducted by Yang et al. (2005), aligned and random electrospun poly (L-lactic acid) (PLLA) microfibrous and nanofibrous scaffolds were created, characterized, and compared.
[7] There are a growing number of methods for the manufacture of micro- and nanostructures (many originating from the semiconductor industry) allowing for the creation of various topographies with controlled size, shape, and chemistry.
[7] In a study conducted by Gomez et al. (2007), microchannels 1 and 2 μm wide and 400 and 800 nm deep created by EBL on PDMS were shown to enhance axon formation of hippocampal cells in culture more so than immobilized chemical cues.
[28] Microdispensing was used to create micropatterns on polystyrene culture dishes by dispensing droplets of adhesive laminin and non-adhesive bovine serum albumin (BSA) solutions.
The micropattern resolution depends on many factors: dispensed liquid viscosity, drop pitch (the distance between the centre of two adjacent droplets in a line or array), and the substrate.
For the purpose of neural tissue engineering degradable materials are preferred whenever possible, because long-term effects such as inflammation and scar could severely damage nerve function.
An advantage of using dextran in biomaterials applications include its resistance to protein adsorption and cell-adhesion, which allows specific cell adhesion to be determined by deliberately attached peptides from ECM components.
[34] AEMA was copolymerized with Dex-MA in order to introduce primary amine groups to provide a site for attachment of ECM-derived peptides to promote cell adhesion.
It is considered an elastomer because it is able to recover from deformation in mechanically dynamic environments and to effectively distribute stress evenly throughout regenerating tissues in the form of microstresses.
Hydrogel degradation was monitored over time by measuring mechanical strength (compressive modulus) and average mesh size from swelling ratio data.
[35] 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.
[16] 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.
[36] 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.
[6] 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.
[39] 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.
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..
[44] These findings may be useful for aligning Schwann cells in a nervous system injury to promote the formation of bands of Bungner, which are crucial for maintaining the endoneurial tube that guides the regrowing axons back to their targets.
A study by Ma, Fitzgerald et al. is the first demonstration of murine neural stem and progenitor cell-derived functional synapse and neuronal network formation on a 3D collagen matrix.
[citation needed] One approach to develop a biomaterial for directing NSC differentiation is to combine extracellular matrix (ECM) components and growth factors.
A very recent study by Nakajima, Ishimuro et al. examined the effects of different molecular pairs consisting of a growth factor and an ECM component on the differentiation of NSCs into astrocytes and neuronal cells.
[51] The results provide valuable information on advantageous combinations of ECM components and growth factors as a practical method for developing a biomaterial for directing differentiation of NSCs.