Where is neural tissue

It stimulates muscle contraction , creates an awareness of the environment, and plays a major role in emotions, memory, and reasoning. To do all these things, cells in nervous tissue need to be able to communicate with each other by way of electrical nerve impulses. The cells in nervous tissue that generate and conduct impulses are called neurons or nerve cells. These cells have three principal parts: the dendrites , the cell body, and one axon. In general, natural polymers offer the advantage of better biocompatibility and bioactivity, while synthetic or non-natural polymers have better mechanical properties and structural stability.

Often, combinations of the two allow for the development of polymeric conduits able to mimic the native physiological environment of healthy neural tissues and, consequently, regulate cell behaviour and support the regeneration of injured nervous tissues. Currently, most of neural tissue engineering applications are in pre-clinical study, in particular for use in the central nervous system, however collagen polymer conduits aimed at regeneration of peripheral nerves have already been successfully tested in clinical trials.

This review highlights different types of natural and synthetic polymers used in neural tissue engineering and their advantages and disadvantages for neural regeneration. Tissue engineering combines principles and techniques of cell biology, material science, and engineering to fabricate tissue substitutes that mimic the structural and physiological nature of native tissue with the fundamental aim to regenerate the functional properties of an injured or diseased tissue [ 1 ].

The regeneration and repair of both the central nervous system CNS and peripheral nervous system PNS remain crucial challenges in tissue engineering. The underlying reason is that both CNS and PNS have limited capacity for self-regeneration in mammals, and lasting functional deficits are common after disease and injury [ 2 ]. Impairments to the CNS can occur in a number of ways, such as trauma due to falls, car accidents, and assaults, which are the leading causes of long-term disability in both urban and rural population worldwide [ 3 ].

In addition, sport-related traumatic brain injuries contribute significantly in developed countries when compared to developing countries [ 3 ]. Neurodegenerative diseases are insidious and progressive disorders and their incidence is on the rise as we have an aging population [ 5 ]. Finally, brain tumours are amongst the leading causes of death and are the second most common cancer found in children [ 10 ]. In the CNS, reactive astrocytes and the formation of an inhibitory glia scar largely prevent regeneration of the damaged tissues [ 11 ].

Most of the current research has been focused towards preventing further damage and on the stabilisation of the affected area, with limited research directed towards understanding reparative processes to enhance recovery of lost functions associated with injury to the CNS. In addition, the PNS is also vulnerable to different kinds of traumatic injuries due to the extensive presence of nerves throughout the body [ 12 ]. The most common types of traumatic peripheral nerve injuries are penetrating injury, crush injury, traction injury, ischemia, laceration, compression, and thermal injury [ 13 , 14 , 15 ].

Trauma due to motor vehicle accidents, penetrating trauma related to violence, falls, and occupational accidents are the most common causes of traumatic injuries to the PNS [ 16 ]. Currently, end-to-end neurorrhaphy is considered the clinical gold standard for the treatment of nerve gaps smaller than 1 cm and autologous nerve grafting is the common treatment for nerve damage exceeding 1 cm [ 18 ].

However, limited availability of nerve grafts, donor site morbidity, possible neuroma formation, and immunological responses are some of the critical issues limiting autologous nerve grafting as a therapeutic approach [ 12 ]. With the limitation of current therapeutic approaches for CNS and PNS injuries to be translated into the clinic, significant work has been directed towards developing novel neural tissue engineering strategies as potential treatments for tissue regeneration.

Polymers, both synthetic and natural in origin, have shown consistent positive results in neural tissue engineering, including neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging [ 19 , 20 , 21 , 22 , 23 , 24 ]. New strategies aimed at the treatment of CNS and PNS injuries include polymeric scaffolds [ 25 , 26 , 27 , 28 , 29 ], hydrogels [ 23 , 30 , 31 , 32 , 33 ], nanoparticles [ 34 , 35 , 36 , 37 ], and nerve conduits [ 20 , 38 , 39 , 40 , 41 ].

The purpose of this review is to present an overview of the literature concerning polymeric applications, focusing particularly on the most recent discoveries, for neural tissue engineering and functional regeneration of nerve tissue.

During the last two decades, enormous progress has been made regarding our understanding of biological mechanisms regulating both CNS and PNS. Polymers have been largely used in neural tissue engineering due to their range of versatility that is unmatched by other biomaterials like metals and ceramics.

The physical, chemical, mechanical, and inherent biological properties vary depending on the different polymer and each of these properties can be variated depending on the application they are being used for, such as 3D cell culture for PC12 cells, drug delivery vehicles, hydrogels, nerve conduits, and scaffolds.

Successful polymeric structures not only offer mechanical support for growing neurites and inhibition of scar tissue, but they also regulate biological cues to guide axonal growth, promote regeneration, and stimulate integration into the existing healthy tissue [ 42 , 43 ], Fig 1. Polymer nanoparticles are considered an optimal and versatile drug delivery system for regions like the brain. Polymer nanoparticles are able to protect therapeutic agents, cross the blood-brain barrier BBB , and efficiently deliver drugs into damaged areas [ 44 , 45 ], Fig.

Polymeric neural probes and electrodes have been successfully used as long-term chronically implantable neuroprosthetic devices for the treatment of neurodegenerative diseases, dystonia, chronic pain, and deep brain stimulation, becoming an invaluable clinical and diagnostic tool [ 46 , 47 ].

Polymeric structure for neural regeneration. Polymeric structures seeded with NGF offer mechanical support for growing neurites that in time will differentiate into fully matured neurons. They regulate biological cues to guide axonal growth and sprouting, to promote the regeneration of the nerve tissue. Polymer coating allows crossing of the BBB.

Uncoated therapeutic drugs are unable to cross the BBB, but polymer nanoparticles are able to protect specific therapeutic agents, cross the BBB, and efficiently deliver drugs into damaged areas. In neural tissue engineering, the use of natural polymers is highly beneficial due to their high biocompatibility and natural biodegradation kinetics combined with chemically tuneable properties.

Often, natural polymers are analogues, if not identical like in the case of collagen, to substances already present in the human body, minimising the risks of cytotoxicity and immunogenic reaction upon implantation in the body [ 43 ]. In neural tissue engineering, natural polymers can fulfil different roles, including matrix formers, gelling agents, or drug release modifiers, and they can be easily adjusted to fit a defect in a difficult physiological geometry, such as the spinal cord [ 48 , 49 ].

Natural polymers applied in neural tissue engineering have different origins, such as extracellular matrix components ECM , like collagen, polymers derived from marine life, like alginate, polymers derived from crustaceans, like chitosan, and polymers derived from insects, like silk. Natural polymers are the most researched type of polymer in neural tissue engineering and they have been preclinically studied at length in numerous animal models, including primates.

In addition, collagen is the only biopolymer currently approved for clinical studies aimed at peripheral nerve regeneration. However, weak mechanical characteristics due to complex chemical structures, thermal sensitivity, and processing difficulties that frequently require use of solvents, hinder the efficacy of natural polymers, prompting researchers to combine them with synthetic or electroconductive polymers.

Table 1 summarises the main natural polymers used in neural tissue engineering and their applications. Humans have 28 proteins known as collagen and the most common is type I, a fibrillary type of collagen, the main component of connective tissues, which provide structure and support throughout the body, including bones, skin, tendons, cartilage, and nerves [ 50 ].

Collagen is a well-known biomaterial in neural tissue engineering. Early applications include the repair of a small 5mm nerve gap in non-human primates through a collagen based nerve guide that proved to be physiologically similar to a graft repair [ 51 , 52 ].

More recently, collagen conduits have been explored as a possible internal filler for neural conduits, increasing the quality of peripheral nerve regeneration over longer gaps. Collagen hydrogels improved the regeneration of a 15mm gap in rat sciatic nerve [ 23 ] and collagen conduits combined with NGF partially reconstructed a 35mm sciatic nerve defect in a dog model [ 53 ].

Collagen is also used in combinations with other biopolymers and proteins. For instance, the electrophysiological evaluation of a collagen-PGA tube confirmed its role as a promising biomaterial for nerve conduits for peripheral nerve regeneration in cats [ 54 ] while a linear ordered collagen scaffold crosslinked with laminin, a key protein of the ECM in the nervous system, guided axonal growth and enhanced nerve regeneration as well as functional recovery in rats [ 28 ].

Collagen has been extensively studied as a biomaterial for neural tissue engineering and as a result, numerous collagen based nerve guides are commercially available on the market for peripheral nerves regeneration. Currently, collagen is the only biopolymer approved for clinical testing in neural tissue engineering.

It is clear that collagen based nerve conduits are the most biocompatible nerve conduit currently available in clinical settings, and its efficacy is often comparable to the clinical gold standard, autologous nerve grafting.

An interesting application of collagen is entubulation, hence the use of magnetically aligned type I collagen gel, achieved by exposing the forming collagen gel to a high-strength magnetic field, as a filler for collagen tubes. This method was successful in small peripheral nerve lesions, improving significantly nerve regeneration in a 6mm nerve gap in mice [ 57 ] and guiding neurite elongation and Schwann cell invasion in vitro [ 58 ] and in vivo [ 59 ]. Fish collagen has attracted interest as an alternative to its bovine counterpart.

Fish collagen can be obtained from the by-products of fish and invertebrate processing, in form of skin, bone, and scales [ 60 ]. Fish collagen has been investigated as a potential biomaterial due to its advantageous biological characteristics, such as excellent biocompatibility, low antigenicity, high level of cell adhesion, and excellent biodegradability [ 61 ].

Fish collagen scaffolds, 2D or 3D, exhibit considerable cell viability, comparable to that of bovine collagen and they have been used for both soft and hard tissue applications [ 61 , 62 ]. However, there is little to no work done on fish collagen for neural tissue engineering and, despite its promising features as a biomaterial, research carried out by Liu et al. For the moment, the findings of Liu et al.

Gelatin is a denatured protein obtained by hydrolysis of animal collagen with either acid or alkaline. Gelatin has a long history of safe use in pharmaceuticals, cosmetics, and food products due to its broad array of advantages, including low cost, availability, high biocompatibility, and biodegradability.

Further, as a denatured product, gelatin is less antigenic than collagen and its chemically modifiable structure allows modulation of cell adhesion and proliferation, improving the biological behaviour of a polymeric device upon implantation [ 64 ]. Primarily, gelatin has found applications in neural tissue engineering as electrospun combinations with other polymers, synthetic or natural in origin.

The use of electrospinning as a fabrication technique for gelatin-based nerve conduits is particularly advantageous because it allows the optimisation and manipulation of mechanical, biological, and kinetic properties. In particular, electrospinning allows control over the orientation of the nanofibres, which is a key component in the creation of a functional scaffold [ 65 ].

Gelatin has also been successfully blended and electrospun with PLA, increasing differentiation into motor neurons lineages and promoting neurite outgrowth [ 72 ]. Polymeric nerve conduit. Components of a polymeric nerve conduit, oriented substratum, support cells, and controlled release of a neural growth factor. Gelatin is often crosslinked with genipin, a non-toxic crosslinker for proteins which enhances both biocompatibility and stability of the crosslinked product.

An interesting application involved electrospun gelatin scaffolds crosslinked with genipin as a platform to provide biochemical cues to seeded cells in a decellularised rat brain ECM. This novel approach showed biocompatibility, cytocompatibility, and differentiative potential, providing tissue-specific signals aimed at expressing neural precursor cells [ 27 ].

Yang et al. The conduit was tested on a short gap, 10 mm, in rat sciatic nerve, but it showed increased motor functionality and histomorphometric assessments confirmed its superiority over silicone tubes [ 73 , 74 ].

Recently, gelatin nanoparticles have been used to enhance the biocompatibility of polymeric scaffolds for neural tissue engineering. In addition, gelatin hydrogels have been used as a printable bioink for advanced bioprinting. Zhu et al. The same research group combined this technology with low level light therapy which exhibited positive effects on the rehabilitation of degenerative nerves and neural disorders [ 78 ].

Elastin-based biomaterials are attracting a lot of interest for tissue engineering applications due to their remarkable properties. Elastin is a structural protein characterised by elasticity, self-assembly, long-term stability, and biological activity. Elastin is an ECM protein that provides elasticity to tissues and organs, therefore it is most abundant in organs where elasticity is a key aspect, such as blood vessels, elastic ligaments, lungs, and skin [ 79 ].

Clearly, incorporation of elastin in biomaterials is majorly significant when the elasticity effects can be exploited, hence its most popular applications are for soft tissue regeneration, such as skin and blood vessels [ 80 , 81 ].

However, elastin-like polypeptides ELPs have found specialised applications in neural tissue engineering. ELPs enhance the biocompatibility and stability of polymeric structures and, due to their tuneable characteristics, act as robust drug delivery systems targeting the brain.

For example, ELPs can be tailor made to be thermally responsive and passively target specific areas of the CNS for treatment of neurodegenerative disorders [ 82 ]. ELPs fused with neurotrophin served as a drug depot, limiting neurotrophin loss due to diffusion, and allowed controlled spatio-temporal drug delivery [ 83 ]. Moreover, the tuneable characteristics of ELPs allowed intranasal administration aimed at therapeutic delivery of drugs to the CNS [ 84 ]. Elastin is not widely used in neural tissue engineering, but ELPs have been recently investigated for novel drug delivery systems and they have found promising applications for thermal inhibition of neurodegenerative disorders.

Therefore, it is conceivable that elastin has found its niche role in neural tissue engineering and its applications could expand to include different devices and regeneration strategies. Hyaluronic acid HA is a glycosaminoglycan found in extracellular tissues in various parts of the human body, where it plays a crucial role in lubrication. HA has been investigated at length for tissue engineering purposes due to its tuneable properties including biodegradability, biocompatibility, bioresorbability, and hydrogel forming ability [ 85 ].

HA has found widespread success in neural tissue engineering, supporting neurite outgrowth, differentiation, and proliferation on different substrates. HA hydrogels enhance the survival rates and proliferation of neural precursors, holding great promise for peripheral nerve regeneration therapies [ 86 , 87 ] and therapeutic approaches to the CNS [ 32 , 88 , 89 ] In particular, HA hydrogels have suitable mechanical properties that influence the differentiation of neural progenitors, opening a new path for therapies targeting neurodegenerative diseases [ 21 , 90 ].

HA can be combined with other natural biopolymers, especially collagen due to the similar nature of the two biomaterials. For instance, Zhang et al.

Combinations of HA and chitosan have also been successful in peripheral nerve regeneration. Li et al treated peripheral nerve crush injury in a rat model using chitosan conduits combined with HA [ 41 ], and Xu et al. Further, blends of HA and biodegradable synthetic polymers, such as PLGA and poly-L-lysine, showed great potential for controlled delivery of drugs aimed at axonal regrowth after spinal cord injury in vitro [ 93 ] and in vivo [ 94 ]. The high biocompatibility of HA has been invaluable to decrease the inflammatory response generated by electroconductive polymers in neural tissue engineering.

Alginate is a naturally occurring anionic biopolymer usually obtained from brown seaweed. Alginate has found growing interest in tissue engineering due to its biocompatibility, low toxicity, low-cost, and gelation characteristics [ 97 ]. However, one of the key disadvantages of alginate is the natural presence of impurities, such as heavy metals, endotoxins, proteins, and polyphenolic compounds, attributable to its marine origin. Therefore, alginate has to be purified in a multi-step extraction procedure to a very high purity in order to minimise possible adverse effects, including immunogenic or inflammatory responses, upon implantation [ 97 ].

Alginate has been used in various biomedical applications, such as drug and protein delivery, wound healing, and as a substrate for cell culture. Alginate gels were also found to be particularly useful for tissue engineering, promoting the regeneration of blood vessels, bones, cartilage, muscle, pancreas, liver, and peripheral nerves.

Suzukia et al. Their studies showed that alginate gels promote peripheral nerve regeneration across a long gap, 50mm, in cat sciatic nerve [ 98 ] and a 10mm nerve gap in rats, increasing the diameter of the regenerating axons [ 99 ]. The group also tested an alginate sponge for the repair of facial nerves in cats. The facial nerve repaired with alginate showed remarkable regeneration but the group notably reduced the size of the nerve defect to 5mm [ ].

Further, alginate sponges implemented to regenerate cavernous nerves in rats showed exceptional regeneration and restoration of erectile function [ ], and they also successfully enhanced elongation of regenerating axons in the spinal cord of young rats [ ], albeit both researches considered a very small gap 2mm.

These findings were confirmed by Hashimoto et al. Alginate has been recently used to create scaffolds for neural applications. Usually, hybrid scaffolds combine the biological characteristics of alginate with the mechanical properties of other biopolymers, both natural and synthetic in origin such as HA or PVA, showing great potential for peripheral nerve regeneration [ , , ]. The leading application of alginate in neural tissue engineering is the treatment of spinal cord injury in rats, where it has been continuously successful in regenerating small nerve gaps, ranging from 2 to 4 mm [ , , , ].

Chitosan is a linear polysaccharide derived by the chemical deacetylation of chitin, the major structural polysaccharide found in crustaceans and shellfish. Chitosan has very interesting properties, such as gel forming capabilities, high adsorption capacity, and biodegradability. Chitosan is extremely biocompatible and non-cytotoxic, as well as presenting antibacterial, antifungal, and antitumor activity [ ].

In addition, chitosan is a versatile biopolymer easily processed into sponges, gels, membranes, beads, and scaffolds, therefore it can be tailor made to suit a specific application. Chitosan hydrogels have been consistently successful in neural tissue engineering, exhibiting cell adhesion, cell interaction, cell survival, and neurite outgrowth [ 76 , , ]. Further, 3D porous chitosan scaffolds combined with NGF had a synergistic effect on the differentiation of neural stem cells and showed potential to regenerate damages in both CNS [ , ] and PNS [ , ].

Often, chitosan is used to enhance the biocompatibility of synthetic polymers with better mechanical characteristics. In addition, chitosan can be chemically modified with ease, thanks to its ability to absorb cell-adhesive molecules, such as collagen, fibronectin, laminin, and genipin. These molecules react with the proteins on the surface of Schwann cells and support their attachment and proliferation, showing potential in directing peripheral nerve regeneration [ , , ].

For example, Skop et al. Chitosan nanoparticles have also been developed for intranasal delivery of therapeutic agents to the brain [ , ]. Chitosan has found recent application as a novel bioink for neural applications and 3D printing of neural constructs. Gu et al. Keratin protein is a polypeptide composed of different amino acids with intermolecular bonding of the disulphide cysteine amino acid and inter and intra-molecular bonding of polar and non-polar acids. Keratin has demonstrated great potential as a biomaterial and it has a long history of applications in the biomedical field due to its high performance biological functionalities.

Keratin also facilitates good cell adhesion and proliferation through its biological characteristics and its versatile amino acid structure can be easily modified to suit a particular tissue [ ].

Keratin was one of the first biomaterials to show promise for neural tissue engineering, due to its biological activities which facilitated the proliferation and infiltration of Schwann cells [ ]. Keratin has found widespread application in the treatment of peripheral nerve injuries. In particular, keratin hydrogels can build biocompatible structures that facilitate neural cell adhesion and axonal ingrowth, while being reliably biodegradable.

Multiple studies showed how keratin hydrogels promote the rapid regeneration of peripheral nerves in vivo , enhancing the activity, attachment, and proliferation of Schwann cells. Keratin hydrogels have the potential to be used clinically to improve conduits repair, producing long-term electrical and histological results equivalent to sensory nerve autograft.

However, some of these older studies [ , ] only considered small nerve gaps 4 mm. Recent studies have tried to bridge a more significant nerve gap. For example, Lin et al. Hill et al. Pace et al.

Keratin can be easily electrospun in combination with other non-natural polymers with stronger mechanical characteristics, enhancing their biocompatibility with excellent results. Electrospun keratin fibres consistently showed good biocompatibility, cell attachment, proliferation, and viability.

Silk is a fibrous structural protein produced by silkworms and spiders with unique properties suitable for a biomaterial. Silk shows great mechanical strength, excellent biocompatibility, minimal immunogenicity, limited bacterial adhesion, and controllable biodegradability [ ]. Further, silk is a versatile material that has been used for the fabrication of biomimetic structures, such as films, hydrogels, scaffolds, nanofibres, and nanoparticles.

In particular, silk hydrogels are soft and sustainable biomaterials often used in neural tissue engineering due to their ability to maintain structural integrity more than other biomaterials, such as fibrin and collagen gels, while being able to elicit increased axonal bundling. Silk hydrogels have been successfully developed as functional scaffolds to support the differentiation of neurons for the regeneration of brain and nerve tissue [ 30 , , ].

Silk hydrogels can also be chemically modified with bioactive peptides, such as IKVAV, that increased cell viability and enhanced neural differentiation [ ]. Further, silk hydrogels showed potential for 3D bioprinting of functional nerve tissue, characterised by high resolution, low feature size, reproducibility, and long term cell viability [ ]. Silk fibroin showed good biocompatibility and absence of cytotoxic effects in vitro , and it can act as tissue engineered nerve guide for potential treatment of CNS injuries.

For example, Benfenati et al. Zhang et al. Recently, Gennari et al. Further, silk fibroin can be easily electrospun for nerve tissue engineering applications. For example, Tian et al. Dinis et al. The nerve graft mechanical behaviors were comparable to those of rat sciatic nerves, showing a similar stress-strain behavior and tensile strength [ 39 ].

Xue et al. Combinations of silk and electroconductive polymers also demonstrated potential for peripheral nerve regeneration. Das et al. In addition, silk coating around brain-penetrating electrodes reduced glial scarring in the CNS, allowing the implantation of electrodes for electrophysiological recording and local stimulation in vivo, used for diagnostic and therapeutic purposes [ , ]. Spider silk is less used in neural tissue engineering mainly due to difficulties in retrieving the material, but its application in vitro has been successful.

For example, Roloff et al. Synthetic polymers used for neural applications can be either biodegradable or non-biodegradable. Initially, neural scaffolds were made of the same materials used for surgical repairs of peripheral nerves and skin grafting [ 49 ]. However, due to advances in biomaterials chemistry and technology, new matrices have been created that better suit the neural environment [ ].

Nowadays neural scaffolds are principally highly aqueous hydrogels, soft polymers that share various similarities and properties with the nerve tissue, and present a strong versatility, which allows their chemistry and architecture to be adjusted according to a specific need [ , , ].

Functionalization of synthetic polymers through surface modification techniques and inclusion of neurotrophic factors expanded the use of synthetic scaffolds to drug delivery and gene delivery vehicles to the CNS [ , , ]. The use of synthetic or non-natural polymers in neural tissue engineering is advantageous because of their mechanical strength and flexibility combined with ease of modification and tailorability, as their structural properties can be modified in many ways, including blending and copolymerization.

Synthetic polymers are also compatible with numerous fabrication techniques, such as wet-spinning, freeze-drying, and electrospinning. However, there are inherent problems with the use of synthetic polymers. Despite synthetic polymers being mainly non-toxic, there are still concerns regarding toxic residual monomers from incomplete polymerisation as well as degradation products and plasticisers.

Therefore, synthetic polymers require intensive and comprehensive testing prior to translation into the clinic. The main synthetic polymers used in neural tissue engineering have been summarized in Table 2 along with their applications. PLA and PGA are thermoplastic polymers characterized by polyesters links of, respectively, lactic or glycolic acid. PLA and PGA were the first biopolymers trialed for regenerate studies using nervous tissue as they had been previously used as an absorbable suture material [ ] and grafting material for wound healing [ ].

PLA has been successfully used to design and construct scaffolds that provide support to Schwann cells, allowing elongation of axons, and to promote vascular growth [ ]. However, PLA scaffolds have been found to be dimensionally or structurally unstable, often shattering and crumpling. Equally, PGA-based nanoconduits have excellent mechanical properties that favor their use in clinical settings, but it was demonstrated that they progressively lose their strength after months upon implantation [ ].

Due to their instable nature, in most cases PGA-based nanoconduits are limited to bridge a small nerve gap [ ]. PLA based multichannel conduits with a nanofibrous microstructure have been used to promote the differentiation of neural stem cells in mature neurons in vitro [ ]. Despite the improved mechanical characteristics, the nanofibrous microstructure was still observed to degrade too fast and it had to be stabilized using a natural polymer, in particular through the use of a gelatin wrap [ ].

PLGA has been used extensively in neural tissue engineering because its characteristics, including permeability, swelling, deformation, and degradation rate, can be controlled by altering the ratio of PLA:PGA to suit specific applications, especially drug delivery microparticles and conduits for nerve regeneration. For instance, multichannel PLGA scaffolds seeded with Schwann cells have been shown to have a synergistic effects on neural regeneration, albeit further studies are needed to aid functional recovery [ , ].

The inherent difficulties that the BBB represents as a protective layer has forced researchers to engineer multiple different approaches that attempt to deliver substantial quantities of drugs to specific parts of the brain.

Hydrogels are three-dimensional cross-linked hydrophilic polymer networks capable of swelling and de-swelling reversibly in water and can retain large volumes of liquid in a swollen state [ ]. They can be designed to have controllable responses and shrink or expand according to the environment they are in [ ].

In neural tissue engineering, the two most common polymers used to create synthetic hydrogels are polyethylene glycol PEG and poly 2-hydroxyethyl methacrylate ; pHEMA. PEG is a biodegradable synthetic polymer of ethylene oxide EO units. PEG is highly biocompatible and well suited for use in hydrogels due to its hydrophilic properties, crucial for nutrient and waste transport, and is also biochemically inert.

In addition, PEG is non-immunogenic and resistant to protein absorption. However, unlike natural polymers used in hydrogels, PEG is not bioactive, hence it is often used in combination with other polymers [ ]. PEG hydrogels have been extensively used for neural tissue engineering.

It is an example of an autoimmune disease. The antibodies produced by lymphocytes a type of white blood cell mark myelin as something that should not be in the body. This causes inflammation and the destruction of the myelin in the central nervous system. As the insulation around the axons is destroyed by the disease, scarring occurs. This is where the name of the disease comes from; sclerosis means hardening of tissue, as occurs in a scar. Multiple scars are found in the white matter of the brain and spinal cord.

Control of the skeletal and smooth musculature is compromised, affecting not only movement, but also control of organs such as the bladder. It is also the result of an autoimmune reaction, but the inflammation is in peripheral nerves.

Sensory symptoms or motor deficits are common, and autonomic failures can lead to changes in the heart rhythm or a drop in blood pressure, especially when standing, which causes dizziness. Nervous tissue contains two major cell types, neurons and glial cells. Neurons are responsible for communication through electrical signals. Glial cells are supporting cells, allowing neuron function.

Though neuron shape varies, neurons are polarized cells, based on the flow of electrical signals along their membrane. In multipolar neurons, dendrites receive signals and pass them to the cell body; signals then propagate along the axon towards the terminal end that synapses with a target cell.

The nervous system has several types of glial cells, categorized by the anatomical division in which they are found. In the CNS, astrocytes, oligodendrocytes, microglia, and ependymal cells perform different functions that support neurons.

Astrocytes maintain the chemical environment around neurons and are crucial for regulating the blood-brain barrier. Oligodendrocytes myelinate neurons, microglia act as phagocytes and play a role in immune surveillance. Ependymal cells filter blood to produce cerebrospinal fluid CSF.

In the PNS, satellite cells maintain the extracellular environment around cell bodies and Schwann cells insulate peripheral axons. The neurons are dynamic cells with the ability to make a vast number of connections and to respond incredibly quickly to stimuli and to initiate movements based on those stimuli. They are the focus of intense research as failures in physiology can lead to devastating illnesses.

Neurons enable thought, perception, and movement. Plants do not move, so they do not need this type of tissue. Microorganisms are too small to have a nervous system. Many are single-celled, and therefore have organelles for perception and movement. The axon contains microtubules and neurofilaments, bounded by a plasma membrane known as the axolemma.

What aspects of the cells in this image react with the stain that makes them the deep, dark, black color, such as the multiple layers that are the myelin sheath?

Multiple sclerosis is a demyelinating disease affecting the central nervous system. What type of cell would be the most likely target of this disease? If this neuron is fully myelinated, what cells would be involved and where?

Skip to content Learning Objectives By the end of this section, you will be able to: Describe how neurons and glial cells function in the nervous system Describe the basic structure of a neuron and how these structures function in a neuron Identify the different types of neurons on the basis of shape List the glial cells of the CNS and describe their function List the glial cells of the PNS and describe their function. External Website Visit this site to learn about how nervous tissue is composed of neurons and glial cells.

Disorders of the…Nervous Tissue. Several diseases can result from the demyelination of axons. The causes of these diseases are not the same; some have genetic causes, some are caused by pathogens, and others are the result of autoimmune disorders. Though the causes are varied, the results are largely similar.

The myelin insulation of axons is compromised, making electrical signaling slower. Chapter Review Nervous tissue contains two major cell types, neurons and glial cells. Interactive Link Questions Visit this site to learn about how nervous tissue is composed of neurons and glial cells. Critical Thinking Questions 1.

In the CNS, oligodendrocytes provide the myelin for axons. Unipolar neurons have a long axon. If half is in the CNS, that half will be myelinated by oligodendrocytes. The half in the PNS will be myelinated by Schwann cells. Previous: Next: