Development of an Injectable Biphasic Hyaluronic Acid-Based Hydrogel With Stress Relaxation Properties for Cartilage Regeneration.

Biomimetic stress-relaxing hydrogels with reversible crosslinks attract significant attention for stem cell tissue regeneration compared with elastic hydrogels. However, stress-relaxing hyaluronic acid (HA)-based hydrogels fabricated using conventional technologies lack stability, biocompatibility, and mechanical tunability. Here, it is aimed to address these challenges by incorporating calcium or phosphate components into the HA backbone, which allows reversible crosslinking of HA with alginate to form interpenetrating networks, offering stability and mechanical tunability for mimicking cartilage. Diverse stress-relaxing hydrogels (τ1/2; SR50, 60-2000 s) are successfully prepared at ≈3 kPa stiffness with self-healing and shear-thinning abilities, favoring hydrogel injection. In vitro cell experiments with RNA sequencing analysis demonstrate that hydrogels tune chondrogenesis in a biphasic manner (hyaline or calcified) depending on the stress-relaxation properties and phosphate components. In vivo studies confirm the potential for biphasic chondrogenesis. These results indicate that the proposed stress-relaxing HA-based hydrogel with biphasic chondrogenesis (hyaline or calcified) is a promising material for cartilage regeneration.

Dual stimuli-responsive mesoporous silica nanoparticles for efficient loading and smart delivery of doxorubicin to cancer with RGD-integrin targeting.

The recent progress in nanoparticle applications, such as tumor-targeting, has enabled specific delivery of chemotherapeutics to malignant tissues with enhanced local efficacy while limiting side effects. However, existing delivery systems leave much room for improvement in terms of achieving enhanced colloidal stability in fluid medium, efficient targeting of intended sites, and effective release of therapeutic drugs into diseased cells. Here, an efficient stimuli-responsive nanocarrier for mammalian cells, termed RGD-NAMs, was developed, which enabled temperature- and pH-sensitive release of drug loads. The RGD-NAMs comprise two parts: a stimuli-responsive copolymer shell (NIBIm-AA-RGD) and drug-container core (MSNs). The RGD-NAMs have a stable drug-loading capacity with a marked difference in the release rate depending on the temperature and pH conditions. The RGD-NAMs also exhibit high colloidal stability in SBF (Stimulated body fluid) solutions and minimal toxicity in skeletal myoblasts (C2C12) and bovine arterial endothelial cells (BAEC). The doxorubicin-loaded RGD-NAMs induced a cytotoxic effect in a dose-dependent manner, which was furthered by an increase in temperature from 37 to 40 °C. Moreover, significant control of the release rate and the amount were achieved through pH change. This novel, smart drug-delivery system with high responsiveness to temperature and pH changes has wide application prospects in biomedical fields, including the theragnosis of tumors and vascular diseases.

Injectable remodeling hydrogels derived from alendronate-tethered alginate calcium complex for enhanced osteogenesis.

A combination of hydrogel materials, and therapeutic agents have been actively reported to facilitate bone defect healing. However, conventionally hydrogels using cross-linker would result in low stability of the hydrogel itself, loss of agents during cross-linking, and complexity of use. In this study, alendronate was tethered to an AlA to improve its bone healing and drug-loading stability. AlA was further functionalized with Ca2+ (AlACa). A mixture of AlACa and alginate formed AlAA hydrogel. The gelation time of AlAA was sufficient for injecting into the defect site. The hydrogel stiffness was controlled, while the stress-relaxation time was fixed. In vitro cell tests demonstrated that the AlAA promoted proliferation and differentiation behaviors. In particular, AlAA showed the best mechanical stiffness with appropriate stress-relaxation and cellular behavior, indicating that it would be beneficial as a scaffold in the bone tissue engineering field.

Wearable CNTs-based humidity sensors with high sensitivity and flexibility for real-time multiple respiratory monitoring.

Sensors, such as optical, chemical, and electrical sensors, play an important role in our lives. While these sensors already have widespread applications, such as humidity sensors, most are generally incompatible with flexible/inactive substrates and rely on conventional hard materials and complex manufacturing processes. To overcome this, we develop a CNT-based, low-resistance, and flexible humidity sensor. The core-shell structured CNT@CPM is prepared with Chit and PAMAM to achieve reliability, accuracy, consistency, and durability, resulting in a highly sensitive humidity sensor. The average response/recovery time of optimized sensor is only less than 20 s, with high sensitivity, consistent responsiveness, good linearity according to humidity rates, and low hysteresis (- 0.29 to 0.30 %RH). Moreover, it is highly reliable for long-term (at least 1 month), repeated bending (over 15,000 times), and provides accurate humidity measurement results. We apply the sensor to smart-wear, such as masks, that could conduct multi-respiratory monitoring in real-time through automatic ventilation systems. Several multi-respiratory monitoring results demonstrate its high responsiveness (less than 1.2 s) and consistent performance, indicating highly desirable for healthcare monitoring. Finally, these automatic ventilation systems paired with flexible sensors and applied to smart-wear can not only provide comfort but also enable stable and accurate healthcare in all environments.

Improved gliotransmission by increasing intracellular Ca2+ via TRPV1 on multi-walled carbon nanotube platforms.

BACKGROUND: Astrocyte is a key regulator of neuronal activity and excitatory/inhibitory balance via gliotransmission. Recently, gliotransmission has been identified as a novel target for neurological diseases. However, using the properties of nanomaterials to modulate gliotransmission has not been uncovered. RESULTS: We prepared non-invasive CNT platforms for cells with different nanotopography and properties such as hydrophilicity and conductivity. Using CNT platforms, we investigated the effect of CNT on astrocyte functions participating in synaptic transmission by releasing gliotransmitters. Astrocytes on CNT platforms showed improved cell adhesion and proliferation with upregulated integrin and GFAP expression. In addition, intracellular GABA and glutamate in astrocytes were augmented on CNT platforms. We also demonstrated that gliotransmitters in brain slices were increased by ex vivo incubation with CNT. Additionally, intracellular resting Ca2+ level, which is important for gliotransmission, was also increased via TRPV1 on CNT platforms. CONCLUSION: CNT can improve astrocyte function including adhesion, proliferation and gliotransmission by increasing resting Ca2+ level. Therefore, our study suggests that CNT would be utilized as a new therapeutic platform for central nervous system diseases by modulating gliotransmission.

Electrical and thermal stimulus-responsive nanocarbon-based 3D hydrogel sponge for switchable drug delivery.

Smart hydrogels that are responsive to various external (e.g. electrical and/or thermal) stimulation have become increasingly popular in recent years for simple, rapid, and precise drug delivery that can be controlled and turned on or off with external stimuli. For such a switchable drug delivery material, highly homogeneous dispersion and distribution of the hydrophobic, electrically conductive nanomaterials throughout a hydrophilic three-dimensional (3D) hydrogel network remains a challenge and is essential for achieving well-connected electrical and thermal conducting paths. Herein we developed electrical and thermal stimulus-responsive 3D hydrogels based on (i) carbon nanotubes (CNTs) as the core unit and an electrical/thermal conductor, (ii) chitosan (Chit) as the shell unit and a hydrophilic dispersant, and (iii) poly(NIPAAm-co-BBVIm) (pNIBBIm) as the drug carrier and a temperature-responsive copolymer. By formulating the CNT-core and Chit-shell units and constructing a CNT sponge framework, uniform distribution and 3D connectivity of the CNTs were improved. The 3D hydrogel based on the CNT sponge, namely the 3D frame CNT-Chit/pNIBBIm hydrogel, delivered approximately 37% of a drug, ketoprofen used for the treatment of musculoskeletal pain, during about 30% shrinkage after electrical and thermal switches on/off and exhibited the best potential for future use in a smart transdermal drug delivery system. The physicochemical, mechanical, electrical, thermal, and biocompatible characteristics of this nanocarbon-based 3D frame hydrogel led to remarkable electrical and thermal stimulus-responsive properties capable of developing an excellent controllable and switchable drug delivery platform for biomedical engineering and medicine applications.

Therapeutic tissue regenerative nanohybrids self-assembled from bioactive inorganic core / chitosan shell nanounits.

Natural inorganic/organic nanohybrids are a fascinating model in biomaterials design due to their ultra-microstructure and extraordinary properties. Here, we report unique-structured nanohybrids through self-assembly of biomedical inorganic/organic nanounits, composed of bioactive inorganic nanoparticle core (hydroxyapatite, bioactive glass, or mesoporous silica) and chitosan shell - namely Chit@IOC. The inorganic core thin-shelled with chitosan could constitute as high as 90%, strikingly contrasted with the conventional composites. The Chit@IOC nanohybrids were highly resilient under cyclic load and resisted external stress almost an order of magnitude effectively than the conventional composites. The nanohybrids, with the nano-roughened surface topography, could accelerate the cellular responses through stimulated integrin-mediated focal adhesions. The nanohybrids were also able to load multiple therapeutic molecules in the core and shell compartment and then release sequentially, demonstrating controlled delivery systems. The nanohybrids compartmentally-loaded with therapeutic molecules (dexamethasone, fibroblast growth factor 2, and phenamil) were shown to stimulate the anti-inflammatory, pro-angiogenic and osteogenic events of relevant cells. When implanted in the in vivo calvarium defect model with 3D-printed scaffold forms, the therapeutic nanohybrids were proven to accelerate new bone formation. Overall, the nanohybrids self-assembled from Chit@IOC nanounits, with their unique properties (ultrahigh inorganic content, nano-topography, high resilience, multiple-therapeutics delivery, and cellular activation), can be considered as promising 3D tissue regenerative platforms.

Carbon nanotube incorporation in PMMA to prevent microbial adhesion.

Although PMMA-based biomaterials are widely used in clinics, a major hurdle, namely, their poor antimicrobial (i.e., adhesion) properties, remains and can accelerate infections. In this study, carboxylated multiwalled carbon nanotubes (CNTs) were incorporated into poly(methyl methacrylate) (PMMA) to achieve drug-free antimicrobial adhesion properties. After characterizing the mechanical/surface properties, the anti-adhesive effects against 3 different oral microbial species (Staphylococcus aureus, Streptococcus mutans, and Candida albicans) were determined for roughened and highly polished surfaces using metabolic activity assays and staining for recognizing adherent cells. Carboxylated multiwalled CNTs were fabricated and incorporated into PMMA. Total fracture work was enhanced for composites containing 1 and 2% CNTs, while other mechanical properties were gradually compromised with the increase in the amount of CNTs incorporated. However, the surface roughness and water contact angle increased with increasing CNT incorporation. Significant anti-adhesive effects (35~95%) against 3 different oral microbial species without cytotoxicity to oral keratinocytes were observed for the 1% CNT group compared to the PMMA control group, which was confirmed by microorganism staining. The anti-adhesive mechanism was revealed as a disconnection of sequential microbe chains. The drug-free antimicrobial adhesion properties observed in the CNT-PMMA composite suggest the potential utility of CNT composites as future antimicrobial biomaterials for preventing microbial-induced complications in clinical settings (i.e., Candidiasis).

Biodegradable and injectable hydrogels as an immunosuppressive drug delivery system.

Cyclosporine A (CsA) is an extremely hydrophobic immunosuppressive drug, whose systemic administration to suppress the activity of T cells and T cell-based immune responses is frequently associated with a number of adverse drug reactions. Local delivery of CsA focused on a specific target organ has been proposed as a possible solution to this problem. In this study, we developed biodegradable sol-gel drug delivery systems, consisting of HA-Ca-Alg hydrogels combining hyaluronic acid calcium complex (HA-Ca) and sodium alginate (Alg-Na) components, for the local sustained delivery of CsA. A HA-Ca complex with very high degree of substitution was prepared by the acid-base reaction of hyaluronic acid and calcium acetate. The gelation was completed within about 2-45 min without external addition of calcium salts such as CaSO4 and CaCl2, indicating the high potential of the present hydrogel systems for drug delivery by injection in vivo. The HA-Ca system was characterized by high-resolution inductively coupled plasma-optical emission spectroscopy, 1H NMR, FT-IR, and thermogravimetric analysis methods. Moreover, the scanning electron microscopy analysis of the HA-Ca-Alg hydrogels showed an irregular porous morphology, with interconnected pores of 50-300 µm width. The sol-gel transition and the maximum viscosity (about 10,000 cP) of the HA-Ca-Alg hydrogels were characterized by examining the time evolution of the viscosity at 37 °C. The hydrolytic degradation of the HA-Ca-Alg hydrogel was also examined at 37 °C. CsA-encapsulated HA-Ca-Alg hydrogels exhibited sustained in vitro release of CsA over 14 days, which was confirmed through in vitro measurements of the activity of murine T cells over 2 weeks. These results show that the present injectable HA-Ca-Alg hydrogels can be used effectively for the sustained delivery of extremely hydrophobic immunosuppressive drugs, including CsA.

Small intestine- and colon-specific smart oral drug delivery system with controlled release characteristic.

In recent years, there has been a significant increase in strategies for the development of small intestine (and colon)-specific oral drug-delivery systems to maximize the efficiency of therapeutic agents and reduce side effects. However, only a few strategies are capable of working in the complicated environment of the human intestinal tract. In this study, the preparation of a basic pH/temperature-responsive co-polymer (p-NIVIm) and its in-vitro-drug delivery function in the pH range of 1-8 and temperature range of 25-42 °C are reported. The basic copolymer was prepared by radical copolymerization of N-isopropyl acryl amide (NIPAAm) and N-vinylimidazole (VIm). The lower critical solution temperature (LCST) of p-NIVIm was higher in stomach pH (~1.0) conditions (36.5-42 °C) and lower in small intestine and/or colon pH (~8.0) conditions (35.8-38.2 °C). The ability to uptake a model protein (BSA) at body temperature and to release it in conditions of 37 °C and pH 1-8 was determined. The drug loading capacity (0.231 mg per 1.0 mg copolymer) and efficiency (92.4%) were high at 37 °C/pH 7. The drug carrier showed a slow release pattern at pH 1 (~0.084 mg; ~35%) and then a sudden release pattern (~0.177 mg; ~73%) at pH 8. The cytotoxicity of p-NIVIm to MCF-7 cells in vitro was minimal at concentrations <168.9 µg/mL after 72 h. The prepared copolymer with its pH-/temperature-responsive protein-entrapping and -releasing behavior at body temperature may potentially be applied as a novel small intestine (and colon)-specific oral drug delivery system.

Simple and cost-effective method of highly conductive and elastic carbon nanotube/polydimethylsiloxane composite for wearable electronics.

The development of various flexible and stretchable materials has attracted interest for promising applications in biomedical engineering and electronics industries. This interest in wearable electronics, stretchable circuits, and flexible displays has created a demand for stable, easily manufactured, and cheap materials. However, the construction of flexible and elastic electronics, on which commercial electronic components can be mounted through simple and cost-effective processing, remains challenging. We have developed a nanocomposite of carbon nanotubes (CNTs) and polydimethylsiloxane (PDMS) elastomer. To achieve uniform distributions of CNTs within the polymer, an optimized dispersion process was developed using isopropyl alcohol (IPA) and methyl-terminated PDMS in combination with ultrasonication. After vaporizing the IPA, various shapes and sizes can be easily created with the nanocomposite, depending on the mold. The material provides high flexibility, elasticity, and electrical conductivity without requiring a sandwich structure. It is also biocompatible and mechanically stable, as demonstrated by cytotoxicity assays and cyclic strain tests (over 10,000 times). We demonstrate the potential for the healthcare field through strain sensor, flexible electric circuits, and biopotential measurements such as EEG, ECG, and EMG. This simple and cost-effective fabrication method for CNT/PDMS composites provides a promising process and material for various applications of wearable electronics.

Ionic and thermo-switchable polymer-masked mesoporous silica drug-nanocarrier: High drug loading capacity at 10°C and fast drug release completion at 40°C.

The preparation of the ideal smart drug-delivery systems were successfully achieved by the in situ co-polymerization of a vinyl group-functionalized mesoporous silica nanoparticle (f-MSN) with 1-butyl-3-vinyl imidazolium bromide (BVIm) and N-isopropylacrylamide (NIPAAm) monomers. The thickness of the capping copolymer layer, poly(NIPAAm-co-BVIm) (p-NIBIm), was controlled at between 2.5nm and 5nm, depending on the monomers/f-MSN ratio in the reaction solution. The finally obtained smart drug-delivery systems are named as p-MSN2.5 and p-MSN5.0 (MSNs integrated by 2.5nm and 5nm p-NIBIm layer in thickness). The key roles of the mesoporous-silica-nanoparticle (MSN) core and the p-NIBIm shell are drug-carrying (or containing) and pore-capping, respectively, and the latter has an on/off function that operates in accordance with temperature changes. According to the swelling- or shrinking-responses of the smart capping copolymer to temperature changes between 10°C and 40°C, the loading and releasing patterns of the model drug cytochrome c were studied in vitro. The developed system showed interesting performances such as a cytochrome-c-loading profile (loading capacity for 3h=26.3% and 19.8% for p-MSN2.5 and p-MSN5.0, respectively) at 10°C and a cytochrome-c-releasing profile (releasing efficiency=>95% within 3 days and 4 days for p-MSN2.5 and p-MSN5.0, respectively) at 40°C. The cytotoxicity of the drug delivery systems, p-MSN2.5 and p-MSN5.0 (in the concentration range of <0.125mg/mL without drug), for human embryonic kidney (HEK 293) cells were minimal in vitro compared with that of a blank MSN. These results may be reasonably applied in the field of specified drug delivery.

Triple Hit with Drug Carriers: pH- and Temperature-Responsive Theranostics for Multimodal Chemo- and Photothermal Therapy and Diagnostic Applications.

Currently there is a strong need for new drug delivery systems, which enable targeted and controlled function in delivering drugs while satisfying highly sensitive imaging modality for early detection of the disease symptoms and damaged sites. To meet these criteria we develop a system that integrates therapeutic and diagnostic capabilities (theranostics). Importantly, therapeutic efficacy of the system is enhanced by exploiting synergies between nanoparticles, drug, and hyperthermia. At the core of our innovation is near-infrared (NIR) responsive gold nanorods (Au) coated with drug reservoirs--mesoporous silica shell (mSi)--that is capped with thermoresponsive polymer. Such design of theranostics allows the detection of the system using computed tomography (CT), while finely controlled release of the drug is achieved by external trigger, NIR light irradiation--ON/OFF switch. Doxorubicin (DOX) was loaded into mSi formed on the gold core (Au@mSi-DOX). Pores were then capped with the temperature-sensitive poly(N-isopropylacrylamide)-based N-butyl imidazolium copolymer (poly(NIPAAm-co-BVIm)) resulting in a hybrid system-Au@mSi-DOX@P. A 5 min exposure to NIR induces polymer transition, which triggers the drug release (pores opening), increases local temperature above 43 °C (hyperthermia), and upregulates particle uptake (polymer becomes hydrophilic). The DOX release is also triggered by drop in pH enabling localized drug release when particles are taken up by cancer cells. Importantly, the synergies between chemo- and photothermal therapy for DOX-loaded theranostics were confirmed. Furthermore, higher X-ray attenuation value of the theranostics was confirmed via X-ray CT test indicating that the nanoparticles act as contrast agent and can be detected by CT.

Preparation of nano/macroporous polycaprolactone microspheres for an injectable cell delivery system using room temperature ionic liquid and camphene.

The nano/macroporous polycaprolactone (PCL) microspheres with cell active surfaces were developed as an injectable cell delivery system. Room temperature ionic liquid (RTIL) and camphene were used as a liquid mold and a porogen, respectively. Various-sized spheres of 244-601µm with pores of various size and shape of 0.02-100µm, were formed depending on the camphene/RTIL ratio (0.8-2.6). To give cell activity, the surface of porous microspheres were further modified with nerve growth factors (NGF) containing gelatin to give a thin NGF/gelatin layer, to which the neural progenitor cells (PC-12) attached and extended their neurites on to the surface layers of the microspheres. The developed microspheres may be potentially applicable as a neuronal cell delivery scaffold for neuron tissue engineering.

Multi-walled carbon nanotubes change morpho-functional and GABA characteristics of mouse cortical astrocytes.

BACKGROUND: Multi-walled carbon nanotubes (MW-CNTs) have been extensively explored for their possible beneficial use in the nervous system. CNTs have shown to modulate neuronal growth and electrical properties, but its effect that varying length of MW-CNTs on primary astrocyte roles have not been clearly demonstrated yet. RESULTS: We investigate here the effect of MW-CNTs on astrocytic morphology, cell-cell interaction and the distribution of intracellular GABA (gamma-amino butyric acid). Primary cultured cortical astrocytes on MW-CNT-coated glass coverslips grow rounder and make more cell-cell interactions, with many cell processes, compared to astrocytes on poly-D-lysine (PDL) coverslips. In addition, intracellular GABA spreads into the cell processes of astrocytes on MW-CNT coverslips. When this GABA spreads into cell processes from the cell body GABA can be released more easily and in larger quantities compared to astrocytes on PDL coverslips. CONCLUSIONS: Our result confirm that MW-CNTs modulate astrocytic morphology, the distribution of astrocytic GABA, cell-cell interactions and the extension of cell processes. CNTs look to be a promising material for use neuroprosthetics such as brain-machine interface technologies.

Carbon Nanotube Nanocomposites with Highly Enhanced Strength and Conductivity for Flexible Electric Circuits.

Carbon nanotubes (CNTs) have an important role in nanotechnology due to their unique properties, retaining the inherent material flexibility, superior strength, and electrical conductivity, unless the bottleneck of CNTs persists and the aggregated structure is overcome. Here, we report on the highly enhanced mechanical and electrical properties of the CNT-chitosan nanocomposites through homogeneous dispersion of CNTs into chitosan solution using a high-pressure homogenizer. The optimal condition is a 50% (w/w) chitosan-CNT film, providing about 7 nm thickness of homogeneous chitosan layer on CNTs, a good tensile strength of 51 MPa, high electrical conductivity under 16 Ω/sq, and a stable bending and folding performance. This CNT-chitosan nanocomposite with highly enhanced properties is an amenable material to fabricate structures of various shapes such as films, sensors, and circuits and also enables a simple and cost-effective approach to improve the performance of a device that presents the first flexible and soft electric circuits yet reported using only CNT-chitosan as the conductor.

Injectable hydrogels derived from phosphorylated alginic acid calcium complexes.

Phosphorylation of sodium alginate salt (NaAlg) was carried out using H3PO4/P2O5/Et3PO4 followed by acid-base reaction with Ca(OAc)2 to give phosphorylated alginic acid calcium complexes (CaPAlg), as a water dispersible alginic acid derivative. The modified alginate derivatives including phosphorylated alginic acid (PAlg) and CaPAlg were characterized by nuclear magnetic resonance spectroscopy for (1)H, and (31)P nuclei, high resolution inductively coupled plasma optical emission spectroscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. CaPAlg hydrogels were prepared simply by mixing CaPAlg solution (2w/v%) with NaAlg solution (2w/v%) in various ratios (2:8, 4:6, 6:4, 8:2) of volume. No additional calcium salts such as CaSO4 or CaCl2 were added externally. The gelation was completed within about 3-40min indicating a high potential of hydrogel delivery by injection in vivo. Their mechanical properties were tested to be ≤6.7kPa for compressive strength at break and about 8.4kPa/mm for elastic modulus. SEM analysis of the CaPAlg hydrogels showed highly porous morphology with interconnected pores of width in the range of 100-800µm. Cell culture results showed that the injectable hydrogels exhibited comparable properties to the pure alginate hydrogel in terms of cytotoxicity and 3D encapsulation of cells for a short time period. The developed injectable hydrogels showed suitable physicochemical and mechanical properties for injection in vivo, and could therefore be beneficial for the field of soft tissue engineering.

Carbon-nanotube-interfaced glass fiber scaffold for regeneration of transected sciatic nerve.

Carbon nanotubes (CNTs), with their unique and unprecedented properties, have become very popular for the repair of tissues, particularly for those requiring electrical stimuli. Whilst most reports have demonstrated in vitro neural cell responses of the CNTs, few studies have been performed on the in vivo efficacy of CNT-interfaced biomaterials in the repair and regeneration of neural tissues. Thus, we report here for the first time the in vivo functions of CNT-interfaced nerve conduits in the regeneration of transected rat sciatic nerve. Aminated CNTs were chemically tethered onto the surface of aligned phosphate glass microfibers (PGFs) and CNT-interfaced PGFs (CNT-PGFs) were successfully placed into three-dimensional poly(L/D-lactic acid) (PLDLA) tubes. An in vitro study confirmed that neurites of dorsal root ganglion outgrew actively along the aligned CNT-PGFs and that the CNT interfacing significantly increased the maximal neurite length. Sixteen weeks after implantation of a CNT-PGF nerve conduit into the 10 mm gap of a transected rat sciatic nerve, the number of regenerating axons crossing the scaffold, the cross-sectional area of the re-innervated muscles and the electrophysiological findings were all significantly improved by the interfacing with CNTs. This first in vivo effect of using a CNT-interfaced scaffold in the regeneration process of a transected rat sciatic nerve strongly supports the potential use of CNT-interfaced PGFs at the interface between the nerve conduit and peripheral neural tissues.

Production of CNT-taxol-embedded PCL microspheres using an ammonium-based room temperature ionic liquid: as a sustained drug delivery system.

We describe a one-pot method for the mass production of polymeric microspheres containing water-soluble carbon-nanotube (w-CNT)-taxol complexes using an ammonium-based room temperature ionic liquid. Polycaprolactone (PCL), trioctylmethylammonium chloride (TOMAC; liquid state from -20 to 240°C), and taxol were used, respectively, as a model polymer, room temperature ionic liquid, and drug. Large quantities of white colored PCL powder without w-CNT-taxol complexes and gray colored PCL powders containing w-CNT-taxol (1:1 or 1:2 wt/wt) complexes were produced by phase separation between the hydrophilic TOMAC and the hydrophobic PCL. Both microsphere types had a uniform, spherical structure of average diameter 3-5µm. The amount of taxol embedded in PCL microspheres was determined by HPLC and (1)H NMR to be 8-12µg per 1.0mg of PCL (loading capacity (LC): 0.8-1.2%; entrapment efficiency (EE): 16-24%). An in vitro HPLC release assay showed sustain release of taxol without an initial burst over 60days at an average rate of 0.003-0.0073mg per day. The viability patterns of human breast cancer cells (MCF-7) for PCTx-1 and -2 showed dose-dependent inhibitory effects. In the presence of PCTx-1 and -2, the MCF-7 cells showed high viability in the concentration level of, respectably, <70 and <5µg/mL.

Multifunctional hybrid nanocarrier: magnetic CNTs ensheathed with mesoporous silica for drug delivery and imaging system.

Here we communicate the development of a novel multifunctional hybrid nanomaterial, magnetic carbon nanotubes (CNTs) ensheathed with mesoporous silica, for the simultaneous applications of drug delivery and imaging. Magnetic nanoparticles (MNPs) were first decorated onto the multiwalled CNTs, which was then layered with mesoporous silica (mSiO2) to facilitate the loading of bioactive molecules to a large quantity while exerting magnetic properties. The hybrid nanomaterial showed a high mesoporosity due to the surface-layered mSiO2, and excellent magnetic properties, including magnetic resonance imaging in vitro and in vivo. The mesoporous and magnetic hybrid nanocarriers showed high loading capacity for therapeutic molecules including drug gentamicin and protein cytochrome C. In particular, genetic molecule siRNA was effectively loaded and then released over a period of days to a week. Furthermore, the hybrid nanocarriers exhibited a high cell uptake rate through magnetism, while eliciting favorable biological efficacy within the cells. This novel hybrid multifunctional nanocarrier may be potentially applicable as drug delivery and imaging systems.