Aligned Electrospun Nanofibers Research Articles

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Data-Driven Machine Learning Approach for Modeling the Production and Predicting the Characteristics of Aligned Electrospun Nanofibers

Data-Driven Machine Learning Approach for Modeling the Production and Predicting the Characteristics of Aligned Electrospun Nanofibers

Correction to: Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits

Correction to: Heparin/Growth Factors-Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin-Based Nerve Guidance Conduits

A Nanofiber‐embedded Microfluidic Platform for Studying Neurobiology

AbstractDue to their biomimetic properties, electrospun nanofibers have been widely used in neurobiology studies. However, mechanistic understanding of cell‐nanofiber interactions is challenging based on the current in vitro culture systems due to the lack of control of spatiotemporal patterning of cells and difficulty in monitoring single cell behavior. To overcome these issues, we apply microfluidic technology in combination with electrospun nanofibers for in vitro studies of interactions between neurons and nanofiber materials. We demonstrate a unique nanofiber embedded microfluidic device which contains patterned aligned or random electrospun nanofibers as a new culture system. With this device, we test how different topographies affect axonal growth. Also, we conduct laser based axotomy on neurons cultured on our device to investigate axonal regeneration. The proposed device could be a useful tool for investigating nerve injury mechanisms and high‐throughput screening of biomaterials or drugs for nerve repair. The knowledge obtained using this device can be applicable to design medical devices such as nerve conduits for effective nerve regeneration.

Dual gradients of bioactive components on electrospun fibers for cell migration and controlled stem cell differentiation

The construction of gradient scaffolds to mimic the in vivo microenvironment for promoting tissue regeneration is attractive, especially by incorporating biochemical cues with physical guidance to manipulate cell behavior. Here, we report a general method to generate dual concentration-gradient of two types of bioactive components on scaffolds composed of uniaxially aligned electrospun nanofibers through layer-by-layer self-assembly. Different layers of collagen (COL) and chondroitin sulfate (CS) are sequentially coated onto the specific positions of uniaxially aligned electrospun polycaprolactone (PCL) nanofibers upon electrostatic attraction. In this case, dual stepwise gradients of COL and CS are generated along the fiber alignment. In demonstrating the potential application, the dual gradients can effectively promote the migration and proliferation of bone marrow stem cells (BMSCs) and spatially control their osteogenic differentiation. This simple strategy for generating dual gradients can be easily extended to different types of gradient scaffolds for bone regeneration and related applications involving cell migration, stem cell differentiation, and tissue interface.

Aligned electrospun poly(l-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways

Delayed wound healing remains a challenge, and macrophages play an important role in the inflammatory process of wound healing. Morphological changes in macrophages can affect their phenotype, but little is known about the underlying mechanism. Aligned electrospun nanofibers have natural advantages in modulating cell morphology. Therefore, the current study constructed aligned electrospun nanofibers that could transform macrophages into elongated shapes. Our results demonstrated that aligned nanofibers without exogenous cytokines could downregulate the proinflammatory M1 phenotype and upregulate the prohealing M2 phenotype in an inflammatory environment. Importantly, our study revealed that aligned electrospun nanofibers could inhibit macrophage M1 polarization via the JAK-STAT and NF-κB pathways. Furthermore, the conditioned medium from macrophages cultured on aligned nanofibers could encourage fibroblast migration, proliferation and collagen secretion. In vivo, aligned nanofibers alleviated the inflammatory microenvironment, promoted angiogenesis and accelerated wound healing in mouse skin defects by modulating macrophage phenotypes. Collectively, aligned electrospun nanofibers can influence macrophage polarization via the JAK-STAT and NF-κB pathways and attenuate the local inflammatory response in skin wounds. This study provides a potential strategy to modulate macrophage polarization and promote wound healing by controlling the topology of biomaterials and offers a new perspective for the application of nanotechnology in wound healing.

Patterning with Aligned Electrospun Nanofibers by Electrostatic Deflection of Fast Jets

Electrospun micro and nanofibers are used in a wide range of applications, but their technological possibilities for printing are incomplete by the limited control over fiber organization and distribution. The use of drum collectors and the inhibition of jet whipping instabilities in near‐field electrospinning (NFES) allow certain degree of control over these parameters. However, fast fibers cannot be directly collected into complex patterns due to the limited degrees of freedom afforded by drum collectors and the relatively slow‐motion control achieved with motorized translation stages used in NFES. Herein, it is demonstrated that electrospun jets of (virtually) any speed can be electrostatically deflected and printed as aligned fibers into a wide variety of structures as fiber tracks characterized by well‐defined width and fiber orientation. The electrostatic deflection of the jet using supplementary electrodes allows a precise control of the track width over a broad range, from submicrometric single nanofiber width to millimeter‐wide tracks. In addition, the fiber alignment, internal structure, and density can be easily adjusted along this fiber track, which opens exciting possibilities toward new applications that require full control on the positioning of fast nanofibers.

The effect of morphology on poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene)-based soft actuators: Films and electrospun aligned nanofiber mats

This paper analyzes soft actuators realized as unimorph cantilever beams, in which the active layer can have two different morphologies, i.e., either an extruded film or an aligned electrospun nanofiber mat of the poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene). Six different soft actuators are fabricated, with active layers of varying thicknesses and morphologies, to study the electrostrictive effect of the polymer and to evaluate the stiffening properties, the mechanical work, and the blocking forces of the actuators when stimulated by different direct current electric fields. The comparison between the different actuators is performed by introducing weight specific properties, i.e., specific stiffness and specific work, showing improved specific properties for the nanofibers-based actuators. Moreover, the blocking forces, the tip deflections, and the leakage currents of the actuators are evaluated when stimulated by alternating current electric fields. The experiments show faster viscoelastic relaxation and lower electrical power consumption for the nanofibers-based actuators. This study concludes that, thank to its electro-mechanical properties, the poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) in the form of aligned electrospun nanofiber mat has high potential to be used as the active layer of electrostrictive unimorph beam soft actuators.

Adipose-Derived Stem Cells Growth and Proliferation Enhancement Using Poly(Lactic-co-Glycolic Acid) (PLGA)/Fibrin Nanofiber Mats

Introduction: A synthetic biomaterial, such as poly(lactic-co-glycolic acid) (PLGA) with superior mechanical properties, along with a natural polymer such as fibrin, which facilitates cell attachment and enhances biocompatibility, can be used in the production of novel composite tissue engineering scaffolds. In this study, we fabricated a PLGA/Fibrin scaffold which was evaluated to the enhancement of adipose-derived stem cells' growth and proliferation. Materials and Methods: 10% polymer solutions with different ratios of PLGA:Fibrin, including 10:0, 9:1, 8:2, and 7:3, were prepared and used in the production of aligned and unaligned electrospun nanofiber scaffolds. Human adipose-derived stem cells (h-ADSCs) were cultured on the scaffolds and they were characterized using FTIR, EDX, SEM, mechanical, hydrophilic, degradation, water absorption, and biocompatibility tests. Results: The obtained scaffolds consisted of homogeneous fibers, without any beads and water droplets. The percentage of porosities and internal correlation of the cavities are not significantly different between aligned and unaligned electrospun scaffolds (P>0.05) and by adding fibrin, these properties are improved, while tensile strength and elasticity are decreased. All the scaffolds are hydrophobic and the highest and lowest swelling rates belong to PLGA/30%Fibrin scaffolds and pure PLGA scaffolds (more than 90% and less than 45%, respectively). There is a significant difference in degradation rates between fibrin-contained scaffolds and pure PLGA scaffolds. Moreover, compared with aligned electrospun scaffolds, a higher degradation rate of unaligned ones was observed. Conclusions: Considering the results of SEM and bio-compatibility experiments, the aligned electrospun PLGA/10%Fibrin scaffold with numerous spindle shape h-ADSCs and unaligned electrospun PLGA/20%Fibrin scaffold with lots of spindle shape cells together with sort of round shape cells are introduced as the optimal options.

Biofabrication of aligned structures that guide cell orientation and applications in tissue engineering

The organized alignment of cells in various tissues plays a significant role in the maintenance of specific functions. To induce such an alignment, ideal scaffolds should simulate the characteristics and morphologies of natural tissues. Aligned structures that guide cell orientation are used to facilitate tissue regeneration and repair. We here review how various aligned structures are fabricated, including aligned electrospun nanofibers, aligned porous or channeled structures, micropatterns and combinations thereof, and their application in nerve, skeletal muscle, tendon, and tubular dentin regeneration. The future use of aligned structures in tissue engineering is also discussed.

Multifunctional Fibroblasts Enhanced via Thermal and Freeze-Drying Post-treatments of Aligned Electrospun Nanofiber Membranes

Parallel fibrous scaffolds play a critical role in controlling the morphology of cells to be more natural and biologically inspired. Among popular tissue engineering materials, poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely investigated in conventional forms due to its biocompatibility, low toxicity, and hydrophilicity. However, the swelling of pHEMA in water remains a major concern. To address this issue, randomly oriented and aligned as-spun pHEMA nanofibrous scaffolds were first fabricated at speeds of 300 and 2000 rpm in this study, which were then post-treated using either a thermal or a freeze-drying method. In cell assays, human dermal fibroblasts (HDFs) adhered to the freeze-drying treated substrates at a significantly faster rate, whereas they had a higher cell growth rate on thermally-treated substrates. Results indicated that the structural properties of pHEMA nanofibrous scaffolds and subsequent cellular behaviors were largely dependent on post-treatment methods. Moreover, this study suggests that aligned pHEMA nanofibrous substrates tended to induce regular fibroblast orientation and unidirectionally oriented actin cytoskeletons over random pHEMA nanofibrous substrates. Such information has predictive power and provides insights into promising post-treatment methods for improving the properties of aligned pHEMA scaffolds for numerous tissue engineering applications.

Towards Poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene)-Based Soft Actuators: Films and Electrospun Aligned Nanofiber Mats

In the pursuit of designing a linear soft actuator with a high force-to-weight ratio and a stiffening behavior, this paper analyzes the electrostrictive effect of the poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene) polymer in the form of film and aligned electrospun nanofiber mat. An experimental setup is realized to evaluate the electrostrictive effect of the specimens disjointly from the Maxwell stress. In particular, an uniaxial load test is designed to evaluate the specimens’ forces produced by their axial contraction (i.e., the electrostrictive effect) when an external electric field is applied, while an uniaxial tensile load test is designed to show the specimens’ stiffening properties. This electro-mechanical analysis demonstrates that both the film and the nanofiber mat are electrostrictive, and that the nanofiber mat exhibits a force-to-weight ratio ∼65% higher than the film and, therefore, a larger electrostrictive effect. Moreover, both the film and the nanofiber mat show a stiffening behavior, which is more evident for the nanofiber mat than the film and is proportional to the weight of the material. This study concludes that, thanks to its electro-mechanical properties, the poly(vinylidene fluoride-trifluoroethylene-chlorotrifluoroethylene), especially in the form of aligned electrospun nanofiber mat, has high potential to be used as electro-active polymer for soft actuators in biomedical and biorobotics applications.

Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair.

Rationale: Peripheral nerve injury (PNI) is a great challenge for regenerative medicine. Nerve autograft is the gold standard for clinical PNI repair. Due to its significant drawbacks, artificial nerve guidance conduits (NGCs) have drawn much attention as replacement therapies. We developed a combinatorial NGC consisting of longitudinally aligned electrospun nanofibers and porcine decellularized nerve matrix hydrogel (pDNM gel). The in vivo capacity for facilitating nerve tissue regeneration and functional recovery was evaluated in a rat sciatic nerve defect model.Methods: Poly (L-lactic acid) (PLLA) was electrospun into randomly oriented (PLLA-random) and longitudinally aligned (PLLA-aligned) nanofibers. PLLA-aligned were further coated with pDNM gel at concentrations of 0.25% (PLLA-aligned/0.25% pDNM gel) and 1% (PLLA-aligned/1% pDNM gel). Axonal extension and Schwann cells migration were evaluated by immunofluorescence staining of dorsal root ganglia cultured on the scaffolds. To fabricate implantable NGCs, the nanofibrous scaffolds were rolled and covered with an electrospun protection tube. The fabricated NGCs were then implanted into a 5 mm sciatic nerve defect model in adult male Sprague-Dawley rats. Nerves treated with NGCs were compared to contralateral uninjured nerves (control group), injured but untreated nerves (unstitched group), and autografted nerves. Nerve regeneration was monitored by an established set of assays, including T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunostaining. Nerve functional recovery was evaluated by walking track analysis.Results: PLLA-aligned/0.25% pDNM gel scaffold exhibited the best performance in facilitating directed axonal extension and Schwann cells migration in vitro due to the combined effects of the topological cues provided by the aligned nanofibers and the biochemical cues retained in the pDNM gel. Consistent results were obtained in animal experiments with the fabricated NGCs. Both the T2 and fractional anisotropy values of the PLLA-aligned/0.25% pDNM gel group were the closest to those of the autografted group, and returned to normal much faster than those of the other NGCs groups. Histological assessment indicated that the implanted PLLA-aligned/0.25% pDNM gel NGC resulted in the largest number of axons and the most extensive myelination among all fabricated NGCs. Further, the PLLA-aligned/0.25% pDNM gel group exhibited the highest sciatic nerve function index, which was comparable to that of the autografted group, at 8 weeks post-surgery.Conclusions: NGCs composed of aligned PLLA nanofibers decorated with 0.25% pDNM gel provided both topological and biochemical guidance for directing and promoting axonal extension, nerve fiber myelination, and functional recovery. Moreover, T2-mapping and DTI metrics were found to be useful non-invasive monitoring techniques for PNI treatment.

Anisotropic Characterizations of Electrospun PAN Nanofiber Mats Using Design of Experiments.

This paper deals with the dielectric and mechanical characterizations of polyacrylonitrile (PAN)-aligned electrospun nanofiber mats. A two factor three level full factorial experiment is conducted to understand the effect of various parameters on dielectric and mechanical responses. These responses are recorded against randomly oriented and aligned nanofiber mats. Improved properties of electrospun mats have applications in the field of energy storage and nanocomposite reinforcement. Dielectric and mechanical characterizations of PAN mats are vital, as the aligned electrospun mats were found to be useful in advanced energy and mechanical reinforcement applications. Therefore, it is paramount to understand the effects of system parameters to these properties. The design of experiment (DoE) includes two factors and three level full factorial experiments with concentrations of PAN solutions at 8 wt.%, 9 wt.%, and 10 wt.%, and speed of the rotating mandrel (collector) at 3 volt (V), 4 V, and 5 V inputs. The electric field intensity used in the experiment is 1 kV/cm. DoE is conducted to understand the nonlinear interactions of parameters to these responses. The dielectric and mechanical characterizations of 8 wt.%, 9 wt.%, and 10 wt.% with different speeds for the original and improved systems are discussed. It was observed that at 9 wt.% and at all mandrel speeds, the dielectric and tensile properties are optimum.

Multi-layer patch with aligned poly (acrylonitrile-co-acrylic acid) nanofibers for lactate detection in human sweat

In this study, polyacrylonitrile (PAN) and poly (acrylonitrile-co-acrylic acid) (P(AN-co-AA)) with different copolymer ratios were synthesized. Aligned electrospun nanofibers of the polymers with diameters from 200 to 300 nm have been produced using two parallel positioned copper wires as collector. The change in resistance between two copper wires was studied with the addition of artificial sweat solution (ASS) on the aligned nanofibers. As the response for 9:1 (acrylonitrile:acrylic acid) P(AN-co-AA) nanofibers was better than the other nanofibers, it was electrospun on a cotton-copper fabric (CCF) to develop the sensor patch. The change in electrical conductivity in response to ASS were studied with varying concentrations of lactate in ASS. The developed multi-layered patch showed 0.94 linear correlation coefficient in the range of 27 to 270 ppm of additional lactate dosage.

Fabrication of random and aligned electrospun nanofibers containing graphene oxide for skeletal muscle cells scaffold

AbstractGraphene oxide (GO)‐based materials have been explored in biomedical applications as active engineered materials for diagnosis and therapy. Although a large number of studies have been carried out in the last years, aspects involving the orientation and elongation of cells on GO immobilized on polymeric nanofibers are still scarce. We investigated the interactions between skeletal muscle cells and GO immobilized on random and aligned electrospun nanofibers of poly(caprolactone) (PCL), a biocompatible and biodegradable polymer. Oxygen plasma was employed to modify the nanofiber polymer surface to enhance the interactions between the PCL fibers and GO. Scanning electron microscopy and confocal microscopy revealed the morphology and orientation of skeletal muscle cells (C2C12 cells) on random and aligned GO/PCL nanofibers. The approach employed here is useful to investigate the interaction of skeletal muscle cells with biocompatible polymer nanofibers modified with GO intended for cell scaffolds and tissue engineering.

Electrospun Core-Shell Nanofibrous Membranes with Nanocellulose-Stabilized Carbon Nanotubes for Use as High-Performance Flexible Supercapacitor Electrodes with Enhanced Water Resistance, Thermal Stability, and Mechanical Toughness.

A high-performance flexible supercapacitor electrode with a core-shell structure is successfully developed from cellulose nanocrystal (CNC)-stabilized carbon nanotubes (CNTs). By incorporating poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAA), a cross-linked nanofibrous membrane (CNT-CNC/PVA-PAA) is prepared as the core material via directional electrospinning, followed by a thermal treatment. The flexible supercapacitor electrodes are eventually fabricated via the in situ polymerization of polyaniline (PANI), which was used as the coating shell material, on the aligned electrospun nanofibers. By taking advantage of the thermally induced esterification cross-linking that occurs among PVA, PAA, and the CNT-CNC nanohybrids, the membranes present with enhanced water resistance, mechanical strength, and thermal stability. After the surface coating of the PANI shell, the optimized PANI@CNT-CNC/PVA-PAA nanofibrous membranes exhibit a large porosity, an enhanced specific surface area, a superior tensile strength of ∼54.8 MPa, and a favorable electroconductivity of ∼0.44 S m-1. As expected, the nanofibrous electrodes with a specific capacitance of 164.6 F g-1 can maintain 91% of the original capacitance after 2000 cycles. The symmetrical solid-state supercapacitor assembled by the nanofibrous electrodes shows an excellent capacitance of 155.5 F g-1 and a remarkable capacitance retention of 92, 90, and 89% after 2000 cycles under flat, bending, and twisting deformations, respectively.

High-performance polyamide-imide films and electrospun aligned nanofibers from an amide-containing diamine

Polyamide-imides (PAIs) are highly desired in many applications because of their superior thermal and mechanical properties. In this work, PAI was prepared from an amide-containing diamine and dianhydride by polycondensation and thermal treatment. Both PAI films and aligned electrospun nanofibers (ANFs) were fabricated. FT-IR was used to determine the structure formation of PAI at different annealing temperatures. DSC and TGA were used to evaluate the thermal properties of PAI, while tensile test was applied to evaluate the mechanical properties of PAI films and ANFs. The results indicated that the PAI possessed both outstanding thermal stability and mechanical properties, which provide opportunities for applications in gas separation, high temperature filtration, reinforcement, etc.

Chitosan/Calcium Silicate Cardiac Patch Stimulates Cardiomyocyte Activity and Myocardial Performance after Infarction by Synergistic Effect of Bioactive Ions and Aligned Nanostructure.

Cardiac tissue engineering (CTE) remains a great challenge to construct a cell-inductive scaffold that has positive effects on cardiac cell behaviors and cardiac tissue repair. In this study, we for the first time demonstrated that Si ions evidently stimulated the expression of cardiac-specific genes and proliferation of neonatal rat cardiomyocytes (NRCMs) at concentration ranges of 0.13-10.78 ppm. Accordingly, the optimized concentrations of calcium silicate (CS) were incorporated into the controllable aligned chitosan electrospun nanofibers, constructing the composite cardiac patch scaffolds. These scaffolds showed synergistic effect of bioactive chemical and structural signals on both cardiomyocytes and endothelial cells with aligned cell morphology and enhanced viability and function characterized by upregulated expressions of cardiac and angiogenic specific markers, improved myofilament structure, and better Ca2+ transients of NRCMs as compared to the scaffolds free of CS component or with disordered structures. The in vivo studies further demonstrated that the NRCM-seeded aligned CS/chitosan cardiac patch evidently improved cardiac function via limiting the scar area and promoting angiogenesis in postmyocardial infarction rats. Conclusively, our study highlights the potential application of bioactive ions and nanostructured biomaterials in CTE, and the CS/chitosan composite cardiac patch may be a promising scaffold for repair of infarcted myocardium.

Nanofiber-Based Proton Exchange Membranes: Development of Aligned Electrospun Nanofibers for Polymer Electrolyte Fuel Cell Applications

To ensure sustainable energy and environments for the future, nanotechnology is continuing to contribute new solutions and prospects. Materials with nanofibrous structures are attractive when it co...