Nanofibrous Microstructure Research Articles

Simvastatin-Releasing Nanofibrous Peptide Hydrogels for Accelerated Healing of Diabetic Wounds.

Wound healing is one of the major global health concerns in diabetic patients. Simvastatin (SMV) is a poorly soluble oral cholesterol-lowering drug that may aid diabetic wound healing. In the current study, a thixotropic peptide hydrogel of Fmoc-diphenylalanine (FmocFF) containing SMV was designed to accelerate skin wound healing effectively and safely in diabetic mice. FmocFF hydrogels were prepared at various concentrations by using the solvent-triggering technique and characterized by spectroscopic methods such as attenuated total reflection Fourier transform infrared (FT-IR) spectroscopy and fluorimetry. Mechanical behaviors were explored by oscillatory rheology. In model mice, the regenerative potential of the FmocFF-SMV hydrogel was evaluated in terms of wound contraction and closure, tissue regeneration, acute and chronic inflammation, granulation, and re-epithelization. The results showed that FmocFF-SMV hydrogels had an entangled nanofibrous microstructure and shear-thinning characteristics. FmocFF-SMV demonstrated a sustained drug release over 7 days. Compared to the unloaded FmocFF hydrogel, treatment with FmocFF-SMV led to superior diabetic wound recovery and reduced inflammation. Therefore, the utilization of the sustained-release FmocFF-SMV hydrogel formulation could become an attractive choice for topical wound therapy in diabetes patients.

An in situ self‐assembled peptide derivative for inhibition of glutathione synthesis and selective enhancement of tumor radiotherapy

AbstractBackgroundInhibition of glutathione (GSH) synthesis in cancer cells considerably improves the efficacy of reactive oxygen species (ROS)‐related tumor therapy. Self‐assembled peptide derivatives can facilitate the efficient delivery and accumulation of small molecular drugs in cancer cells.MethodsSelf‐assembling modules were covalently linked to the GSH‐biosynthesis inhibitor l‐buthionine sulfoximine (BSO) by solid‐phase synthesis to form the self‐assembling peptide derivative Nap‐DFDFpY‐GG‐BSO (Nano‐BSO@ in situ). Subsequently, its enzyme‐instructed self‐assembly in vitro and on cell surfaces were confirmed, and its intracellular GSH depletion and radiotherapy‐sensitizing effects were determined.ResultsNano‐BSO@ in situ successfully self‐assembles into a hydrogel with a nanofibrous microstructure upon incubation with alkaline phosphatase (ALP) at a critical concentration of 9.84 μM. Furthermore, it selectively self‐assembles in situ on HeLa cells with high ALP expression. At a concentration of 50 μM, Nano‐BSO@ in situ decreases intracellular GSH levels by 80%, ∼2.3 times more than free BSO. Meanwhile, pretreatment of HeLa cells with 50 μM Nano‐BSO@ in situ for 24 h results in a radiotherapy sensitization enhancement ratio to γ‐rays of 2.09.ConclusionsA novel in situ self‐assembling peptide derivative for GSH depletion and selective enhancement of tumor radiotherapy was constructed. The excellent GSH‐depletion ability and remarkable radiotherapy‐enhancement performance indicate that Nano‐BSO@ in situ is a promising selective sensitizer for ROS‐related treatment of tumor cells with high ALP expression.

Scalable manufacturing of light, multifunctional cellulose nanofiber aerogel sphere with tunable microstructure for microwave absorption

Thanks to the high strength-to-weight ratio and aspect ratio, large specific surface area, and sustainability, cellulose nanofibers (CNFs) have incomparable advantages in constructing multifunctional aerogels. However, efficient utilization of the nanofibrous microstructure for developing aerogels of high-performance is extremely challenging due to the severe agglomeration of CNF. Here, a novel type of ultralight aerogel spheres composed of fibrous or sheet-like CNF-derived nanocarbon are manufactured via a facile, scalable drop-freezing followed by a pyrolysis approach. The nanostructured carbons of tunable morphologies are accomplished, endowing the aerogel spheres with abundant hierarchical pores, large specific surface area, and three-dimensional conductive skeletons with ultralight nature. In addition to the high-efficiency adsorption of the organic dye, the aerogel spheres enable a controllable and excellent electromagnetic wave absorption. The aerogels composed of coexisting fibrous and layered nanocarbons display an effective absorption bandwidth of 6.16 GHz, and a minimum reflection loss of −66.3 dB at the thickness of 2.14 mm, and a merely 1 wt% filler loading, which significantly outperforms that of other carbon-based absorbers. This work thus suggests a new avenue for designing high-performance, sustainable multifunctional biomass-based aerogels, demonstrating extensive application potentials in adsorption, electromagnetic absorption, and aerospace.

Engineering vascularized dermal grafts by integrating a biomimetic scaffold and Wharton's jelly MSC-derived endothelial cells.

Tissue engineering aims to generate functional tissue constructs with the necessary scaffold properties for cell colonization and the establishment of a vascular network. However, treatment of tissue defects using synthetic scaffolds remains a challenge mainly due to insufficient and slow vascularization. Our previous study developed a macroporous silk fibroin scaffold with a nanofibrous microstructure, and demonstrated that the nanofibrous structure can promote the viability of endothelial cells (ECs) and guide cell migration. Further studies are needed to clarify the effect of scaffold microstructures on cell-mediated vascularization. Here, we investigated the efficacy of EC-seeded nanofibrous scaffolds in improving vascularization in vivo. ECs derived from induced human Wharton's Jelly mesenchymal stem cells served as a potential source for cell transplantation. The cell-seeded scaffolds were implanted into dermal defects of SD rats, demonstrating that the multiscale hierarchical design significantly improved the capacity of transplanted cells to promote and accelerate neovascularization and dermal reconstruction via enhancing cell infiltration, collagen deposition and growth factor expression. Our findings provide new insight into the development of degradable macroporous composite materials with 3D microstructures as tissue engineering scaffolds with enhanced vascularization functions, and also provide new treatment options for cell transplantation.

Bioinspired Fabrication of Calcium-Doped TiP Coating with Nanofibrous Microstructure to Accelerate Osseointegration.

Bioinspired by the morphology of osteoclast-resorbed bone surfaces, we prepared a calcium-doped titanium phosphate (Ca-TiP) coating, which consists of a nanofibrous network, on titanium (Ti) substrate via a simple two-step hydrothermal method, trying to mimic natural bone compositionally and microstructurally. The in vitro studies show that the Ca-TiP coating with synergistic features of nanofibrous biomimetic topography and surface chemistry could elicit intensively osteogenic behavior and responses including enhanced cell adhesion, spreading, and proliferation as well as alkaline phosphatase (ALP) activity and up-regulated expression of bone-related genes, which inevitably benefit the formation of new bone and the quality of osseointegration. When the two control groups are compared in vivo, the significantly improved new bone formation in the early stage and the much stronger interfacial bonding with the surrounding bone for Ca-TiP coating suggest that Ca-TiP coating modified Ti implants hold great potential for orthopedic and dental applications.

The effect of oxygen plasma pretreatment on the properties of mussel-inspired polydopamine-decorated polyurethane nanofibers

AbstractIn this study, polyurethane (PU) scaffolds were fabricated by electrospinning technology and modified through the deposition of polydopamine (PDA) on the activated surface under oxygen plasma treatment. Herein, the effect of the modification process on the homogeneous surface coating and the changes in the physicochemical and biological properties were evaluated. Morphological observations demonstrated decoration of the nanofibrous microstructure with PDA, while the uniformity and homogeneity of the deposited layer increased after plasma oxygen treatment. Hydrophilicity measurements and swelling ratio indicated a remarkable improvement in the interaction of scaffolds with water molecules when the PDA coating is applied on the surface of the treated nanofibers. The biomineralization of the samples was characterized using X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) images. It was found that PDA has the capability for mineralization, and the amount of deposited hydroxyapatite increased as a function of PDA content. Thein vitroevaluation of constructs indicated great improvement in cell-scaffold interactions, biocompatibility, and alkaline phosphatase activity after coating the PDA on the plasma-modified matrix. These results suggest that PDA coating, especially after oxygen plasma treatment, improves the physicochemical andin vitroproperties of PU scaffolds for bone tissue engineering application.

Tensile properties of tungsten-rhenium wires with nanofibrous structure

In this study, the mechanical properties of tungsten-rhenium wires with nanofibrous microstructure were investigated at both room temperature (RT) and 800°C. The strengthening mechanism associated to the nanofibrous microstructure was discussed. The results showed that the tungsten-rhenium wires with nanofibrous grains exhibited a very high tensile strength reaching values of 3.5 GPa and 4.4 GPa for the coarse (grains diameter of 240 nm) and fine (grains diameter of 80 nm) wires, respectively. With increasing the temperature from RT to 800°C, the tensile strength decreased slightly but still held high values (1.8 GPa and 3.8 GPa). All the fracture surfaces exhibited apparent necking and characteristics of spear-edge shaped fracture surface, indicating excellent ductility of the wires. A model of the strengthening mechanism of these tungsten-rhenium wires was proposed.

Supramolecular nanofibers of dexamethasone derivatives to form hydrogel for topical ocular drug delivery.

The low bioavailability exhibits by conventional ocular formulation owing to rapid precorneal clearance and lower corneal permeability can be overcame by the application of the gelling system. In the present study, a prodrug supramolecular hydrogel derived from succinated dexamethasone (Dex-SA) was fabricated using a pH hydrolytic strategy and explored as a "self-delivery" system for ophthalmic drugs. The self-assembled Dex-SA supramolecular hydrogel exhibited a typical nano-fibrous microstructure and was thixotropic. Both dexamethasone (Dex) and Dex-SA prodrug sustainably released from Dex-SA supramolecular hydrogel in a period of 120 h in vitro release study, and the initial pH value of hydrogel significantly influence on the release ratio of Dex/Dex-SA. Furthermore, the lyophilized Dex-SA supramolecular hydrogel displayed long-term stability without causing any apparent hydrolysis of Dex-SA at -20 °C over 30 day and quickly re-formed a hydrogel after dissolving into aqueous solution. The formed Dex-SA supramolecular hydrogel had lower cytotoxicity than Dex at drug concentration up to 2.5 mM, and exhibited a comparable anti-inflammatory efficacy to a Dex sodium phosphate (Dexp) aqueous solution in lipopolysaccharide-activated RAW264.7 macrophages. Topical instillation of the Dex-SA supramolecular hydrogel showed excellent intraocular biocompatibility and it was not an irritant in rabbit eyes. More importantly, the Dex-SA supramolecular hydrogel provided a prolonged precorneal retention and significantly enhanced the ocular bioavailability over Dexp aqueous solution after topical instillation. Overall, this work illustrates an effective approach for the development of prodrug supramolecular hydrogels to extend the precorneal retention and enhance ocular bioavailability of drugs after topical instillation.

Nano-fibrous and ladder-like multi-channel nerve conduits: Degradation and modification by gelatin

We recently fabricated multi-channel PLLA nerve conduits (NCs, conduits diameter: ~3mm, channels diameter: ~200μm) with nano-fibrous microstructure (NNCs) and ladder-like microstructure (LNCs), and found the nanofibers in the NNCs promote differentiation of nerve stem cells (NSCs) into neurons. In the present study, we evaluated the degradation profile of NNCs and LNCs, and observed that NNCs degraded too fast to implant. To delay the degradation and retain the nano-scale effect of NNCs, we used gelatin to wrap (2% w/v gelatin) or embed (8% w/v gelatin) NNCs and LNCs via vacuum infusion and chemical cross-linking with genipin. NNCs-wrapped maintained their original nano-fibrous microstructure, but NNCs-embedded presented a porous morphology without nanofibers appearing. Incorporation of gelatin did not change their compressive moduli, but increased the creep recovery ratios of LNCs and NNCs. In vitro degradation revealed that integrity was maintained and the mass loss was <5% for NNCs-wrapped after 10weeks, in comparison with 15% mass loss and collapsed structure of the pure NNCs after 4weeks. Meanwhile, there were no obvious changes in the degradation of LNCs with modification. Nerve stem cells (NSCs) were then seeded onto the six NCs represented as: NNCs, NNCs-wrapped, NNCs-embedded, LNCs, LNCs-wrapped, and LNCs-embedded. Immunocytochemistry analysis demonstrated that gelatin coating enhanced the adhesion and proliferation of NSCs, and the NNCs-wrapped scaffold promoted the differentiation proportion of NSCs into neurons from 25.8% (on pure NNCs) to 53.4% after 14days of seeding. On the other hand, only 14.3% of neurons were derived from the differentiation of the seeded NSCs on the NNCs-embedded. NNCs-wrapped would be a good choice for future studies in nerve injury repair in vivo due to its appropriate degradation rate, flexibility, and nano-scale effect.

Graphene-incorporated nanofibrous hybrid membrane with enhanced properties

Graphene has been highlighted as an additive material to ameliorate functions of biomaterials due to its unique structure and superelasticity. In this study, graphene at different concentration (up to 10%) was incorporated into a hybrid membrane composed of chitosan and silica xerogel to enhance the functionality of the hybrid membrane for guided bone regeneration (GBR) through in situ sol-gel technique. The effect of graphene incorporation was evaluated in terms of morphology, mechanical property, and biological property. In SEM observation, graphene (G)-incorporated membranes showed macroporous structure and nanofibrous microstructure which could allow protein to attach onto membrane more efficiently. The hybrid membrane containing 10% graphene was found to have highly porous and nanofibrous structure with the highest level of protein adsorption. These G-incorporated membranes also showed improved mechanical properties compared to hybrid membrane only (control) in wet state. However, the tensile strength and elongation were decreased when 10% graphene was incorporated into the hybrid membrane. Both in vitro and in vivo tests confirmed that G-incorporated membranes had similar biological properties to those of osteogenic hybrid membrane with excellent GBR ability. These findings demonstrate that proper amount of graphene could be added to hybrid membrane to increase loading capacity of biomolecules for guided bone regeneration. Open image in new window

Chitosan microspheres with an extracellular matrix-mimicking nanofibrous structure as cell-carrier building blocks for bottom-up cartilage tissue engineering.

Scaffolds for tissue engineering (TE) which closely mimic the physicochemical properties of the natural extracellular matrix (ECM) have been proven to advantageously favor cell attachment, proliferation, migration and new tissue formation. Recently, as a valuable alternative, a bottom-up TE approach utilizing cell-loaded micrometer-scale modular components as building blocks to reconstruct a new tissue in vitro or in vivo has been proved to demonstrate a number of desirable advantages compared with the traditional bulk scaffold based top-down TE approach. Nevertheless, micro-components with an ECM-mimicking nanofibrous structure are still very scarce and highly desirable. Chitosan (CS), an accessible natural polymer, has demonstrated appealing intrinsic properties and promising application potential for TE, especially the cartilage tissue regeneration. According to this background, we report here the fabrication of chitosan microspheres with an ECM-mimicking nanofibrous structure for the first time based on a physical gelation process. By combining this physical fabrication procedure with microfluidic technology, uniform CS microspheres (CMS) with controlled nanofibrous microstructure and tunable sizes can be facilely obtained. Especially, no potentially toxic or denaturizing chemical crosslinking agent was introduced into the products. Notably, in vitro chondrocyte culture tests revealed that enhanced cell attachment and proliferation were realized, and a macroscopic 3D geometrically shaped cartilage-like composite can be easily constructed with the nanofibrous CMS (NCMS) and chondrocytes, which demonstrate significant application potential of NCMS as the bottom-up cell-carrier components for cartilage tissue engineering.

Fabrication and evaluation of PLLA multichannel conduits with nanofibrous microstructure for the differentiation of NSCs in vitro.

Nerve conduits (NCs) with multiple longitudinally aligned channels, being mimicking the natural nerves anatomical structure, have been attracted more and more attentions. However, some specific structural parameters of a conduit that would be beneficial for further improvement of neural tissue regeneration were not comprehensively considered. Using a systematized device and combining low-pressure injection molding and thermal-induced phase separation, we fabricated 33-channel NCs (outer diameter 3.5 mm, channel diameter 200 μm) with different well-defined microscopic features, including NCs with a nano-fibrous microstructure (NNC), NCs with microspherical pores and nano-fibrous pore walls (MNC), and NCs with a ladder-like microstructure (LNC). The porosities of these NCs were ∼90% and were independent of the fine microstructures, whereas the pore size distributions were clearly distinct. The adsorption of bovine serum albumin for the NNC was a result of having the highest specific surface area, which was 3.5 times that of the LNC. But the mechanical strength of NNC was lower than that of two groups because of a relative high crystallinity and brittle characteristics. In vitro nerve stem cells (NSCs) incubation revealed that 14 days after seeding the NSCs, 31.32% cells were Map2 positive in the NNC group, as opposed to 15.76% in the LNC group and 23.29% in the MNC group. Addition of NGF into the culture medium, being distinctive specific surface area and a high adsorption of proteon for NNC, 81.11% of neurons derived from the differentiation of the seeded NSCs was obtained. As a result of imitating the physical structure of the basement membrane of the neural matrix, the nanofibrous structure of the NCs has facilitated the differentiation of NSCs into neurons.

Highly porous TiO2 nanofibres with a fractal structure

TiO2 nanofibres were prepared using a templating method with tetraisopropylorthotitanate(TiPT) as a precursor. The preparation comprises liquid phase deposition oncellulose fibres followed by thermal removal of the cellulose template. The obtainedTiO2 fibrous substance consists of micron-size fibres with a microstructure of nanofibres. It wasdemonstrated that nanofibres are basically formed through the aggregation ofTiO2 nanoparticles and nanorods into chain structures during thethermal treatment process. The measured surface area of theTiO2 fibreswas about 250 m2 g−1. It was shown that the pore size distribution is multi-scale and a fractal morphologywas demonstrated with two fractal regimes with dimensions of 1.78 and 2.97for sizes below and above 7.5 nm, respectively. The crystalline phase of theTiO2 nanofibres, as well as the nanoparticles in the solution, could be controlled by the pH of thesolution. A pH of 1.2 resulted in rutile phase, while a pH of 1.8 resulted in anatase phase.