methods reduce scarring of the nerves, increasing the functionality of the nerves to transmit action potentials after reconnection. two types of materials are used in guidance methods of pns regeneration: natural-based materials and synthetic materials. natural-based materials are modified scaffolds stemming from ecm components and glycosaminoglycans. laminin, collagen, and fibronectin, which are all ecm components, guide axonal development and promote neural stimulation and activity. other molecules that have the potential to promote nerve repair are: hyaluronic acid, fibrinogen, fibrin gels, self-assembling peptide scaffolds, alginate, agarose, and chitosan. synthetic materials also provide another method for tissue regeneration in which the graft's chemical and physical properties can be controlled. since the properties of a material may be specified for the situation in which it is being used, synthetic materials are an attractive option for pns regeneration. the use of synthetic materials come with certain concerns, such as: easy formation of the graft material into the necessary dimensions, biodegradable, sterilizable, tear resistant, easy to operate with, low risk of infection, and low inflammation response due to the material. the material must also maintain the channel during the nerve regeneration. currently, the materials most commonly researched mainly focus on polyesters, but biodegradable polyurethane, other polymers, and biodegradable glass are also being investigated. other possibilities for synthetic materials are conducting polymers and polymers biologically modified to promote cell axon growth and maintain the axon channel. difficulty of research because there are so many factors that contribute to the success or failure of neural tissue engineering, there are many difficulties that arise in using neural tissue engineering to treat cns and pns injuries. first, the therapy needs to be delivered to the site of the injury. this means that the injury site needs to be accessed by surgery or drug delivery. both of these methods have inherent risks and difficulties in themselves, compounding the problems associated with the treatments. a second concern is keeping the therapy at the site of the injury. stem cells have a tendency to migrate out of the injury site to other sections of the brain, thus the therapy is not as effective as it could be as when the cells stay at the injury site. additionally, the delivery of stem cells and other morphogens to the site of injury can cause more harm than good if they induce tumorigenesis, inflammation, or other unforeseen effects. finally, the findings in laboratories may not translate to practical clinical treatments. treatments are successful in a lab, or even an animal model of the injury, may not be effective in a human patient. related research modeling brain tissue development in vitro two models for brain tissue development are cerebral organoids and corticopoiesis. these models provide an "in vitro" model for normal brain development, but they can be manipulated to represent neural defects. therefore, the mechanisms behind healthy and malfunctioning development can be studied by researchers using these models. these tissues can be made with either mouse embryonic stem cells (esc)s or human escs. mouse escs are cultured in a protein called sonic hedgehog inhibitor to promote the development of dorsal forebrain and study cortical fate. this method has been shown to produce axonal layers that mimic a broad range of cortical layers. human esc-derived tissues use pluripotent stem cells to form tissues on scaffold, forming human ebs. these human esc-derived tissues are formed by culturing human pluripotent ebs in a spinning bioreactor. targeted reinnervation targeted reinnervation is a method to reinnervate the neural connections in the cns and pns, specifically in paralyzed patients and amputees using prosthetic limbs. currently, devices are being investigated that take in and record the electrical signals that are propagated through neurons in response to a person's intent to move. this research could shed light on how to reinnervate the neural connections between severed pns nerves and the connections between the transplanted 3d scaffolds into the cns.