Synthetic Amphoteric Cryogels as an Antidote against Acute Heavy Metal Poisoning.

The effectiveness of an amphoteric cryogel (AAC) as an oral sorbent (enerosorbent) for the treatment of acute poisoning of small animals (rats) with heavy metals (HMs) was studied in in vivo experiments. The morphological structure of the cryogel was examined using scanning electron microscopy/energy-dispersive X-ray analysis and confocal microscopy. The use of the cryogel in the treatment of rats administered an LD50 dose of Cd(NO3)2, CsNO3, Sr(NO3)2, or HgCl2 in aqueous solution showed their high survival rate compared to the control group, which did not receive such treatment. The histological and chemical analysis of internal tissues and the biochemical analysis of the blood of the experimental animals showed the effectiveness of the cryogel in protecting the animals against the damaging effect of HMs on the organism comparable with unithiol, a chelating agent based on 2,3-dimercapto-1-propane sulfonic acid sodium salt (DMPS) approved for the treatment of acute poisoning with some heavy metals.

Surface-Functionalized Conducting Nanofibers for Electrically Stimulated Neural Cell Function.

Strategies involving the inclusion of cell-instructive chemical and topographical cues to smart biomaterials in combination with a suitable physical stimulus may be beneficial to enhance nerve-regeneration rate. In this regard, we investigated the surface functionalization of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV)-based electroconductive electrospun nanofibers coupled with externally applied electrical stimulus for accelerated neuronal growth potential. In addition, the voltage-dependent conductive mechanism of the nanofibers was studied in depth to interlink intrinsic conductive properties with electrically stimulated neuronal expressions. Surface functionalization was accomplished using 3-aminopropyltriethoxysilane (APTES) and 1,6-hexanediamine (HDA) as an alternative to costly biomolecule coating (e.g., collagen) for cell adhesion. The nanofibers were uniform, porous, electrically conductive, mechanically strong, and stable under physiological conditions. Surface amination boosted biocompatibility, 3T3 cell adhesion, and spreading, while the neuronal model rat PC12 cell line showed better differentiation on surface-functionalized mats compared to nonfunctionalized mats. When coupled with electrical stimulation (ES), these mats showed comparable or faster neurite formation and elongation than the collagen-coated mats with no-ES conditions. The findings indicate that surface amination in combination with ES may provide an improved strategy to faster nerve regeneration using MEH-PPV-based neural scaffolds.

Novel nanostructured iron oxide cryogels for arsenic (As(III)) removal.

Novel macroporous iron oxide nanocomposite cryogels were synthesized and assessed as arsenite (As(III)) adsorbents. The two-step synthesis method, by which a porous nanonetwork of iron oxide is firstly formed, allowed a homogeneous dispersion of the iron oxide in the cryogel reaction mixture, regardless of the nature of the co-polymer forming the cryogel structure. The cryogels showed excellent mechanical properties, especially the acrylamide-based cryogel. This gel showed the highest As(III) adsorption capacity, with the maximum value estimated at 118 mg/g using the Langmuir model. The immobilization of the nanostructured iron oxide gel into the cryogel matrix resulted in slower adsorption kinetics, however the cryogels offer the advantage of a stable three-dimensional structure that impedes the release of the iron oxide nanoparticles into the treated effluent. A preliminary toxicity evaluation of the cryogels did not indicate any apparent inhibition of human hepatic cells activity, which together with their mechanical stability and high adsorption capacity for As(III) make them excellent materials for the development of nanoparticle based adsorption devices for drinking water treatment.

Investigation of the adsorption capacity of the enterosorbent Enterosgel for a range of bacterial toxins, bile acids and pharmaceutical drugs.

Oral intestinal adsorbents (enterosorbents) are orally administered materials which pass through the gut where they bind (adsorb) various substances. The enterosorbent Enterosgel (Polymethylsiloxane polyhdrate) is recommended as a symptomatic treatment for acute diarrhoea and chronic diarrhoea associated with irritable bowel syndrome (IBS). Since 1980's there have been many Enterosgel clinical trials, however, the detailed mechanism of Enterosgel action towards specific toxins and interaction with concomitantly administered medications has not been fully investigated. Our in vitro study assessed the adsorption capacity of Enterosgel for bacterial enterotoxins and endotoxin, bile acids and interaction with the pharmaceutical drugs; Cetirizine and Amitriptyline hydrochloride. Our data demonstrate the good adsorption capacity of Enterosgel for bacterial toxins associated with gastrointestinal infection, with a lower than the comparator charcoal Charcodote capacity for bile acids whose levels can be raised in IBS patients. Adsorption capacity for the two drugs varied but was significantly lower than Charcodote. These findings suggest that the mechanism of Enterosgel action in the treatment of gastrointestinal infection or IBS is adsorption of target molecules followed by removal from the body. This therapy offers a drug free approach to prevention and treatment of infectious and chronic non-infectious diseases, where intestinal flora and endotoxemia play a role.

Investigation of rice husk derived activated carbon for removal of nitrate contamination from water.

Development of porous carbons with high specific surface area (>1200mg-1) targeted at nitrate removal from aqueous solutions is investigated by chemical activation of carbonized rice husk. Potassium carbonate is used as activating and desilicating agent. The effect of post-synthetic treatment by gas phase ammoxidation with ozone/ammonia or oxidation with concentrated nitric acid followed by nitrification with urea on main physicochemical properties and on the effectiveness of the activated carbons in nitrate removal is compared with those determined for a pristine activated carbonized rice husk sample. The two-fold enhancement of nitrate removal by the urea-modified activated carbon in comparison with pristine and ammoxidated sample is in direct correlation with the development of surface basic groups.

Amine-Functionalized Electrically Conductive Core-Sheath MEH-PPV:PCL Electrospun Nanofibers for Enhanced Cell-Biomaterial Interactions.

In the present study, a conducting polymer, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) along with a biodegradable polymer poly(ε-caprolactone) (PCL) was used to prepare an electrically conductive, biocompatible, bioactive, and biodegradable nanofibrous scaffold for possible use in neural tissue engineering applications. Core-sheath electrospun nanofibers of PCL as the core and MEH-PPV as the sheath, were surface-functionalized with (3-aminopropyl) triethoxysilane (APTES) and 1,6-hexanediamine to obtain amine-functionalized surface to facilitate cell-biomaterial interactions with the aim of replacing the costly biomolecules such as collagen, fibronectin, laminin, and arginyl-glycyl-aspartic acid (RGD) peptide for surface modification. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed the formation of core-sheath morphology of the electrospun nanofibers, whereas Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) revealed successful incorporation of amine functionality after surface functionalization. Adhesion, spreading, and proliferation of 3T3 fibroblasts were enhanced on the surface-functionalized electrospun meshes, whereas the neuronal model rat pheochromocytoma 12 (PC12) cells also adhered and differentiated into sympathetic neurons on these meshes. Under a constant electric field of 500 mV for 2 h/day for 3 consecutive days, the PC12 cells displayed remarkable improvement in the neurite formation and outgrowth on the surface-functionalized meshes that was comparable to those on the collagen-coated meshes under no electrical signal. Electrical stimulation studies further demonstrated that electrically stimulated PC12 cells cultured on collagen I coated meshes yielded more and longer neurites than those of the unstimulated cells on the same scaffolds. The enhanced neurite growth and differentiation suggest the potential use of these scaffolds for neural tissue engineering applications.

Preparation of liposomes containing small gold nanoparticles using electrostatic interactions.

The development of liposome-nanoparticle colloid systems offers a versatile approach towards the manufacture of multifunctional therapeutic platforms. A strategy to encapsulate small metallic nanoparticles (<4nm) within multilamellar vesicles, effected by exploiting electrostatic interactions was investigated. Two liposome-gold nanoparticle (lipo-GNP) systems were prepared by the reverse-phase evaporation method employing cationic or anionic surface functionalised particles in combination with oppositely charged lipid compositions with subsequent post-formulation PEGylation. Structural characterisation using electron microscopy and elemental analysis revealed a regular distribution of GNPs between adjacent lipid bilayers of intact liposomes. Nanoparticle encapsulation efficacy of the two lipo-GNP systems was revealed to be significantly different (p=0.03), evaluated by comparing the ratio of measured lipid to gold concentration (loading content) determined by a colorimetric assay and atomic emission spectroscopy, respectively. It was concluded that the developed synthetic strategy is an effective approach for the preparation of liposome-nanoparticle colloids with potential to control the relative concentration of encapsulated particles to lipids by providing favourable electrostatic interactions.

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis.

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uraemic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins. Small and large monoliths were synthesised using an optimised ratio of lignin binder to porous resin of 1 in 4. Small monoliths showing combined significant IS, p-CS and IL-6 adsorption were used to measure haemocompatibility in an ex vivo healthy donor blood perfusion model, assessing coagulation, platelet, granulocyte, T cells and complement activation, haemolysis, adsorption of electrolytes and plasma proteins. The small monoliths were tested in a naive rat model and showed stable blood gas values, blood pressure, blood biochemistry and the absence of coagulopathies. These monoliths were scaled up to a clinically relevant size and were able to maintain adsorption of protein bound uraemic toxins IS, PCS and high molecular weight cytokines TNF-α and IL-6 over 240 min using a flow rate of 300 ml min-1 without platelet activation. The nanoporous monoliths where haemocompatible and retained adsorptive efficacy on scale up with negligible pressure drop across the system indicating potential for use as an in-line device to improve haemodialysis efficacy by adsorption of otherwise poorly removed uraemic toxins.

Properties of Water Bound in Hydrogels.

In this review, the importance of water in hydrogel (HG) properties and structure is analyzed. A variety of methods such as ¹H NMR (nuclear magnetic resonance), DSC (differential scanning calorimetry), XRD (X-ray powder diffraction), dielectric relaxation spectroscopy, thermally stimulated depolarization current, quasi-elastic neutron scattering, rheometry, diffusion, adsorption, infrared spectroscopy are used to study water in HG. The state of HG water is rather non-uniform. According to thermodynamic features of water in HG, some of it is non-freezing and strongly bound, another fraction is freezing and weakly bound, and the third fraction is non-bound, free water freezing at 0 °C. According to structural features of water in HG, it can be divided into two fractions with strongly associated and weakly associated waters. The properties of the water in HG depend also on the amounts and types of solutes, pH, salinity, structural features of HG functionalities.

Nano carriers for drug transport across the blood-brain barrier.

Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully discussed.

Carbon-cryogel hierarchical composites as effective and scalable filters for removal of trace organic pollutants from water.

Effective technologies are required to remove organic micropollutants from large fluid volumes to overcome present and future challenges in water and effluent treatment. A novel hierarchical composite filter material for rapid and effective removal of polar organic contaminants from water was developed. The composite is fabricated from phenolic resin-derived carbon microbeads with controllable porous structure and specific surface area embedded in a monolithic, flow permeable, poly(vinyl alcohol) cryogel. The bead-embedded monolithic composite filter retains the bulk of the high adsorptive capacity of the carbon microbeads while improving pore diffusion rates of organic pollutants. Water spiked with organic contaminants, both at environmentally relevant concentrations and at high levels of contamination, was used to determine the purification limits of the filter. Flow through tests using water spiked with the pesticides atrazine (32 mg/L) and malathion (16 mg/L) indicated maximum adsorptive capacities of 641 and 591 mg pollutant/g carbon, respectively. Over 400 bed volumes of water contaminated with 32 mg atrazine/L, and over 27,400 bed volumes of water contaminated with 2 µg atrazine/L, were treated before pesticide guideline values of 0.1 µg/L were exceeded. High adsorptive capacity was maintained when using water with high total organic carbon (TOC) levels and high salinity. The toxicity of water filtrates was tested in vitro with human epithelial cells with no evidence of cytotoxicity after initial washing.

Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state-of-the-art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects. Carbon nanotubes (CNTs) are an emerging novel material for biomedical applications currently being developed for a range of therapeutic technologies including scaffolds for engineering and interfacing with neurological tissues. CNTs possess a unique set of physicochemical properties that could be useful within nerve repair conduits. This progress report aims to evaluate and consolidate the current literature pertinent to CNTs as a biomaterial for supporting peripheral nerve regeneration. The report is presented in the context of the state-of-the-art in nerve repair conduit design; outlining how CNTs may enhance the performance of next generation peripheral nerve repair conduits.

A simple method for the production of large volume 3D macroporous hydrogels for advanced biotechnological, medical and environmental applications.

The development of bulk, three-dimensional (3D), macroporous polymers with high permeability, large surface area and large volume is highly desirable for a range of applications in the biomedical, biotechnological and environmental areas. The experimental techniques currently used are limited to the production of small size and volume cryogel material. In this work we propose a novel, versatile, simple and reproducible method for the synthesis of large volume porous polymer hydrogels by cryogelation. By controlling the freezing process of the reagent/polymer solution, large-scale 3D macroporous gels with wide interconnected pores (up to 200 µm in diameter) and large accessible surface area have been synthesized. For the first time, macroporous gels (of up to 400 ml bulk volume) with controlled porous structure were manufactured, with potential for scale up to much larger gel dimensions. This method can be used for production of novel 3D multi-component macroporous composite materials with a uniform distribution of embedded particles. The proposed method provides better control of freezing conditions and thus overcomes existing drawbacks limiting production of large gel-based devices and matrices. The proposed method could serve as a new design concept for functional 3D macroporous gels and composites preparation for biomedical, biotechnological and environmental applications.

Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein A for removal of anthrax toxin protective antigen.

Polymeric cryogels are efficient carriers for the immobilization of biomolecules because of their unique macroporous structure, permeability, mechanical stability and different surface chemical functionalities. The aim of the study was to demonstrate the potential use of macroporous monolithic cryogels for biotoxin removal using anthrax toxin protective antigen (PA), the central cell-binding component of the anthrax exotoxins, and covalent immobilization of monoclonal antibodies. The affinity ligand (protein A) was chemically coupled to the reactive hydroxyl and epoxy-derivatized monolithic cryogels and the binding efficiencies of protein A, monoclonal antibodies to the cryogel column were determined. Our results show differences in the binding capacity of protein A as well as monoclonal antibodies to the cryogel adsorbents caused by ligand concentrations, physical properties and morphology of surface matrices. The cytotoxicity potential of the cryogels was determined by an in vitro viability assay using V79 lung fibroblast as a model cell and the results reveal that the cryogels are non-cytotoxic. Finally, the adsorptive capacities of PA from phosphate buffered saline (PBS) were evaluated towards a non-glycosylated, plant-derived human monoclonal antibody (PANG) and a glycosylated human monoclonal antibody (Valortim(®)), both of which were covalently attached via protein A immobilization. Optimal binding capacities of 108 and 117 mg/g of antibody to the adsorbent were observed for PANG attached poly(acrylamide-allyl glycidyl ether) [poly(AAm-AGE)] and Valortim(®) attached poly(AAm-AGE) cryogels, respectively, This indicated that glycosylation status of Valortim(®) antibody could significantly increase (8%) its binding capacity relative to the PANG antibody on poly(AAm-AGE)-protien-A column (p < 0.05). The amounts of PA which remained in the solution after passing PA spiked PBS through PANG or Valortim bound poly(AAm-AGE) cryogel were significantly (p < 0.05) decreased relative to the amount of PA remained in the solution after passing through unmodified as well as protein A modified poly(AAm-AGE) cryogel columns, indicates efficient PA removal from spiked PBS over 60 min of circulation. The high adsorption capacity towards anthrax toxin PA of the cryogel adsorbents indicated potential application of these materials for treatment of Bacillus anthracis infection.

The in vitro characterization of a gelatin scaffold, prepared by cryogelation and assessed in vivo as a dermal replacement in wound repair.

A sheet gelatin scaffold with attached silicone pseudoepidermal layer for wound repair purposes was produced by a cryogelation technique. The resulting scaffold possessed an interconnected macroporous structure with a pore size distribution of 131 ± 17 µm at one surface decreasing to 30 ± 8 µm at the attached silicone surface. The dynamic storage modulus (G') and mechanical stability were comparable to the clinical gold standard dermal regeneration template, Integra®. The scaffolds were seeded in vitro with human primary dermal fibroblasts. The gelatin based material was not only non-cytotoxic, but over a 28 day culture period also demonstrated advantages in cell migration, proliferation and distribution within the matrix when compared with Integra®. When seeded with human keratinocytes, the neoepidermal layer that formed over the cryogel scaffold appeared to be more advanced and mature when compared with that formed over Integra®. The in vivo application of the gelatin scaffold in a porcine wound healing model showed that the material supports wound healing by allowing host cellular infiltration, biointegration and remodelling. The results of our in vitro and in vivo studies suggest that the gelatin based scaffold produced by a cryogelation technique is a promising material for dermal substitution, wound healing and other potential biomedical applications.

An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis.

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20-100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care.

Synthesis and application of hydride silica composites for rapid and facile removal of aqueous mercury.

The adsorption of ionic mercury(II) from aqueous solution on functionalized hydride silicon materials was investigated. The adsorbents were prepared by modification of mesoporous silica C-120 with triethoxysilane or by converting alkoxysilane into siloxanes by reaction with acetic acid. Mercury adsorption isotherms at 208C are reported, and maximum mercury loadings were determined by Langmuir fitting. Adsorbents exhibited efficient and rapid removal of ionic mercury from aqueous solution, with a maximum mercury loading of approximately 0.22 and 0.43 mmol of Hg g1 of silica C-120 and polyhedraloligomeric silsesquioxane (POSS) xerogel, respectively. Adsorption efficiency remained almost constant from pH 2.7 to 7. These inexpensive adsorbents exhibiting rapid assembly, low pH sensitivity, and high reactivity and capacity, are potential candidates as effective materials for mercury decontamination in natural waters and industrial effluents.

Nanoporous activated carbon beads and monolithic columns as effective hemoadsorbents for inflammatory cytokines.

The aim of the present study was to develop and investigate nanoporous activated carbon materials for their ability to adsorb inflammatory cytokines directly from blood, for a range of therapeutic applications, including: systemic inflammatory response syndrome (SIRS) related to sepsis, cardio-pulmonary by-pass surgery, or ischemic reperfusion injury. Building on the previously established relationship between the porous structure of beaded polymer-derived activated carbon and its capacity to adsorb inflammatory molecules, we have developed and characterized monolithic porous carbon columns produced from the same polymer precursor matrix as carbon microbeads. The monolithic columns developed were assessed for their ability to adsorb inflammatory molecules from blood in a circulating system. Preliminary findings demonstrated good removal of the inflammatory cytokines IL-8 (100% removal), IL-6 (80% removal), and TNF (51% removal) from blood. The efficiency of cleansing is dependent on the size of the adsorbed molecule and the porous structure of the monolith, highlighting their potential for use as a hemoadsorption device.

Cryogels: morphological, structural and adsorption characterisation.

Experimental results on polymer, protein, and composite cryogels and data treatment methods used for morphological, textural, structural, adsorption and diffusion characterisation of the materials are analysed and compared. Treatment of microscopic images with specific software gives quantitative structural information on both native cryogels and freeze-dried materials that is useful to analyse the drying effects on their structure. A combination of cryoporometry, relaxometry, thermoporometry, small angle X-ray scattering (SAXS), equilibrium and kinetic adsorption of low and high-molecular weight compounds, diffusion breakthrough of macromolecules within macroporous cryogel membranes, studying interactions of cells with cryogels provides a consistent and comprehensive picture of textural, structural and adsorption properties of a variety of cryogels. This analysis allows us to establish certain regularities in the cryogel properties related to narrow (diameter 0.4100 µm) with boundary sizes within modified life science pore classification. Particular attention is paid to water bound in cryogels in native superhydrated or freeze-dried states. At least, five states of water - free unbound, weakly bound (changes in the Gibbs free energy-ΔG<0.5-0.8 kJ/mol) and strongly bound (-ΔG>0.8 kJ/mol), and weakly associated (chemical shift of the proton resonance δ(H)=1-2 ppm) and strongly associated (δ(H)=3-6 ppm) waters can be distinguished in hydrated cryogels using (1)H NMR, DSC, TSDC, TG and other methods. Different software for image treatment or developed to analyse the data obtained with the adsorption, diffusion, SAXS, cryoporometry and thermoporometry methods and based on regularisation algorithms is analysed and used for the quantitative morphological, structural and adsorption characterisation of individual and composite cryogels, including polymers filled with solid nano- or microparticles.

In vitro biocompatibility of multiwalled carbon nanotubes with sensory neurons.

Multiwalled carbon nanotubes (MWCNTs) possess unique properties rendering them a potentially useful biomaterial for neurobiological applications such as providing nanoscale contact-guidance cues for directing axon growth within peripheral nerve repair scaffolds. The in vitro biocompatibility of MWCNTs with postnatal mouse spinal sensory neurons was assessed for this application. Cell culture medium conditioned with MWCNTs was not significantly toxic to dissociated cultures of postnatal mouse dorsal root ganglia (DRG) neurons. However, exposure of DRG neurons to MWCNTs dispersed in culture medium resulted in a time- and dose-dependent reduction in neuronal viability. At 250 µg mL⁻¹, dispersed MWCNTs caused significant neuronal death and unusual neurite morphologies illustrated by immunofluorescent labelling of the cytoskeletal protein beta (III) tubulin, however, at a dose of 5 µg mL⁻¹ MWCNTs were nontoxic over a 14-day period. DRG neurons grown on fabricated MWCNT substrates produced neurite outgrowths with abnormal morphologies that were significantly inferior in length to neurons grown on the control substrate laminin. This evidence demonstrates that to be utilized as a biomaterial in tissue scaffolds for nerve repair, MWCNTs will require robust surface modification to enhance biocompatibility and growth promoting properties.