Electrospun fibers:a guiding scaffold for research and regeneration of the spinal cord

The challenge to regenerating the nervous system compared to other tissues in the body is the complexity of the tissue. For example, a small amount of scar tissue formation after an injury to the skin may have few negative side effects, but any scar tissue in the central nervous system is a major physical and chemical barrier to nerve regeneration （Sofroniew, 2009）.

Electrospun Fibers Control Drug Delivery for Tissue Regeneration and Cancer Therapy

Versatile strategies have been developed to construct electrospun fiber-based drug delivery systems for tissue regeneration and cancer therapy.We first introduce the construction of electrospun fiber scaffolds and their various structures,as well as various commonly used types of drugs.Then,we discuss some representative strategies for controlling drug delivery by electrospun fibers,with specific emphasis on the design of endogenous and external stimuli-responsive drug delivery systems.Afterwards,we summarize the recent progress on controlling drug delivery with electrospun fiber scaffolds for tissue engineering,including soft tissue engineering(such as skin,nerve,and cardiac repair)and hard tissue engineering(such as bone,cartilage,and musculoskeletal systems),as well as for cancer therapy.Furthermore,we provide future development directions and challenges facing the use of electrospun fibers for controlled drug delivery,aiming to provide insights and perspectives for the development of smart drug delivery platforms and improve clinical therapeutic effects in tissue regeneration and cancer therapy.

Programmable immune activating electrospun fibers for skin regeneration

Immune cells play a crucial regulatory role in inflammatory phase and proliferative phase during skin healing.How to programmatically activate sequential immune responses is the key for scarless skin regeneration.In this study,an“Inner-Outer”IL-10-loaded electrospun fiber with cascade release behavior was constructed.During the inflammatory phase,the electrospun fiber released a lower concentration of IL-10 within the wound,inhibiting excessive recruitment of inflammatory cells and polarizing macrophages into anti-inflammatory phenotype“M2c”to suppress excessive inflammation response.During the proliferative phase,a higher concentration of IL-10 released by the fiber and the anti-fibrotic cytokines secreted by polarized“M2c”directly acted on dermal fibroblasts to simultaneously inhibit extracellular matrix overdeposition and promote fibroblast migration.The“Inner-Outer”IL-10-loaded electrospun fiber programmatically activated the sequential immune responses during wound healing and led to scarless skin regeneration,which is a promising immunomodulatory biomaterial with great potential for promoting complete tissue regeneration.

A Perspective:Electrospun Fibers for Repairing Spinal Cord Injury

Patients with spinal cord injury(SCI)are suffering disability and accompanying complications.Due to the complex biological processes and inhibitory microenvironment after SCI,advances in clinical treatment show obvious limitations for achieving a successful repair.Herein,we summarize recent advances in engineering strategies of using electrospun nanofibers to promote the neural regeneration and functional recovery after SCI.We firstly introduce the pathological mechanism of SCI and thus point out the challenges on the regeneration of the nerve.We then discuss the regenerative approaches by combining electrospun nanofibrous scaffolds with physical cues,biochemical cues(e.g.,cells,growth factors and other biomolecules),external stimuli,and supporting materials filling in the inner lumen of the scaffolds.All these strategies have indicated their potentials to enhance the efficacy of repairing the SCI.At last,we provide a perspective on the future direction for designing the electrospun nanofibrous scaffolds in combination with imaging systems to realize the in-situ monitoring of regeneration progress for further improving the treatment outcome.

Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury

The complex pathophysiology of spinal cord injury may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. Many efforts have been performed to design and develop suitable scaffolds for spinal cord regeneration, keeping in mind that the reconstruction of a pro-regenerative environment is the key challenge for an effective neurogenesis. The aim of this review is to outline the main features of an ideal scaffold, based on biomaterials, produced by the electrospinning technique and intended for the spinal cord regeneration. An overview of the poly- mers more investigated in the production of neural fibrous scaffolds is also provided.

A biomimetic basementmembrane consisted of hybrid aligned nanofibers andmicrofibers with immobilized collagen IV and laminin for rapid endothelialization

Rapid formation of a continuous endothelial cell(EC)monolayer with healthy endothelium function on the luminal surface of vascular implants is imperative to improve the longtime patency of small-diameter vascular implants.In the present study,we combined the contact guidance effects of aligned nanofibers,which enhance EC adhesion and proliferation because of its similar fiber scale with native vascular basement membranes,and aligned microfibers,which could induce EC elongation effectively and allow ECs infiltration.It was followed by successive immobilization of collagen IV and laminin to fabricate a biomimetic basement membrane(BBM)with structural and compositional biomimicry.The hemolysis assay and platelet adhesion results showed that the BBM exhibited excellent hemocompatibility.Meanwhile,the adhered human umbilical vein endothelial cells(HUVECs)onto theBBMaligned along the orientation of the microfibers with an elongated morphology,and the data demonstrated that the BBM showed favorable effects on EC attachment,proliferation,and viability.The oriented EC monolayer formed on the BBM exhibited improved antithrombotic capability as indicated by higher production of nitric oxide and prostacyclin(PGI2).Furthermore,fluorescence images indicated that HUVECs could infiltrate into the BBM,implying theBBM’s ability to enhance transmural endothelialization.Hence,theBBMpossessed the properties to regulate ECbehaviors and allow transmural ingrowth,demonstrating the potential to be applied as the luminal surface of small-diameter vascular implants for rapid endothelialization.

Electrospun fiber membrane with asymmetric NO release for the differential regulation of cell growth

The high incidence of cardiovascular disease has led to significant demand for synthetic vascular grafts in clinical applications.Anti-proliferation drugs are usually loaded into devices to achieve desirable anti-thrombosis effects after implantation.However,the non-selectiveness of these conventional drugs can lead to the failure of blood vessel reconstruction,leading to potential complications in the long term.To address this issue,an asymmetric membrane was constructed through electro-spinning techniques.The bilayer membrane loaded and effectively released nitric oxide(NO),as hoped,from only one side.Due to the short diffusion distance of NO,it exerted negligible effects on the other side of the membrane,thus allowing selective regulation of different cells on both sides.The released NO boosted the growth of endothelial cells(ECs)over smooth muscle cells(SMCs)-while on the side where NO was absent,SMCs grew into multilayers.The overall structure resembled a native blood vessel,with confluent ECs as the inner layer and layers of SMCs to support it.In addition,the membrane preserved the normal function of ECs,and at the same time did not exacerbate inflammatory responses.By preparing this material type that regulates cell behavior differentially,we describe a new method for its application in the cardiovascular field such as for artificial blood vessels.

Surface Modification of Electrospun Poly(L-lactide)/Poly(ε-caprolactone)Fibrous Membranes by Plasma Treatment and Gelatin Immobilization

Biopolymer fibers have great potential for technical applications in biomaterials.The surface properties of fibers are of importance in these applications.In this study,electrospun poly(L-lactide)(PLLA)/poly(ε-caprolactone)(PCL)membranes were modified by cold plasma treatment and coating gelatin to improve the surface hydrophilic properties.The morphologies of the fibers were observed by scanning electron microscopy(SEM).Atomic force microscopy(AFM)was employed to show the surface characteristics of the fibers.The chemical feature of the fibrous membrane surfaces was examined by X-ray photoelectron spectroscopy(XPS).The surface wettability of the fibrous membrane was also characterized by water contact angle measurements.All these results show that plasma treatment can have profound effects on the surface properties of fibrous membranes by changing their surface physical and chemical features.Gelatin-PLLA/PCL membrane has great potential in applications of tissue engineering scaffolds.

Matrix Effect on Polydiarylfluorenes Electrospun Hybrid Microfibers: From Morphology Tuning to High Explosive Detection Efficiency

Precisely optimizing the morphology of functional hybrid polymeric systems is crucial to improve its photophysical property and further extend their optoelectronic applications. The physic-chemical property of polymeric matrix in electrospinning (ES) processing is a key factor to dominate the condensed structure of these hybrid microstructures and further improve its functionality. Herein, we set a flexible poly(ethylene oxide) (PEO) as the matrix to obtain a series of polydiarylfluorenes (including PHDPF, PODPF and PNDPF) electrospun hybrid microfibers with a robust deep-blue emission. Significantly different from the rough morphology of their poly(N-vinylcarbazole) (PVK) ES hybrid fibers, polydiarylfluorenes/PEO ES fibers showed a smooth morphology and small size with a diameter of 1∼2 µm. Besides, there is a relatively weak phase separation under rapid solvent evaporation during the ES processing, associated with the hydrogen-bonded-assisted network of PEO in ES fibers. These relative “homogeneous” ES fibers present efficient deep-blue emission (PLQY>50%), due to weak interchain aggregation. More interestingly, low fraction of planar (β) conformation appears in the uniform PODPF/PEO ES fibers, induced by the external traction force in ES processing. Meanwhile, PNDPF/PEO ES fibers present a highest sensitivity than those of other ES fibers, associated with the smallest diameter and large surface area. Finally, compared to PODPF/PVK fibers and PODPF/PEO amorphous ES fibers, PODPF/PEO ES fibers obtained from DCE solution exhibit an excellent quenching behavior toward a saturated DNT vapor, mainly due to the synergistic effect of small size, weak separation, β-conformation formation and high deep-blue emission efficiency.

Melting Temperature of Individual Electrospun Poly(vinylidene fluoride) Fibers Studied by AFM-based Local Thermal Analysis

Thermal properties such as melting temperature can well reflect the microstructure of the polymer material, and have practical implications in the application of nanofibers. In this work, we investigated the melting temperature of individual electrospun poly(vinylidene fluoride)(PVDF) nanofibers with diameters ranging from smaller than 200 nm to greater than 2 μm by the local thermal analysis technique. The PVDF fibers obtained under four different conditions were found to crystallize into α and β phases, and the fiber mats showed typical values in the crystallinity and Tm with no significant difference among the four. However, analyses at single fiber level revealed broad distribution in diameter and Tm for the fibers produced under identical electrospinning condition. The Tm of individual nanofibers was found to remain constant at large diameters and increase quickly when reducing the fiber diameter toward the nanoscale, and Tm values of 220-230 ℃ were observed for the thinnest nanofibers, much higher than the typical values reported for bulk PVDF. The Tm and molecular orientation at different positions along a beaded fiber were analyzed, showing a similar distribution pattern with a minimum at the bead center and higher values when moving toward both directions. The results indicate that molecular orientation is the driving mechanism for the observed correlation between the Tm and the diameter of the nanofibers.

Electrospinning Nanofiber Membrane Reinforced PVA Composite Hydrogel with Preferable Mechanical Performance for Oil-Water Separation

Nowadays hydrogels have been attracting the massive interest in oil-water separation due to their robust hydrophilicity and fantastic underwater oiliness features.However,the weak toughness and tensile strength shortcomings of hydrogels have thus inhibited their actual applicability.For this reason,we successfully fabricated the electrospun nanofiber membrane-reinforced PVA composite hydrogels.The PVA-PAN composite hydrogel has exhibited the excellent tensile strength and friction performance,separately enhancing 174.2%of the tensile strength,and reducing 20.7%of the friction coefficient and 58.7%of wear volume relative to the neat PVA hydrogel.Furthermore,the pull-out experiments indicated that the PAN nanofiber membrane exerted a stronger interface bonding effect with PVA hydrogel.The oil-water separation evaluation test showed that the separation efficiency reached up to 97.6%for treating the SA-100 lubricating oil/water system.

静电纺纤维滴鼻液实现脑室内给药

Adequate drug delivery across the blood–brain barrier(BBB) is a critical factor in treating central nervous system(CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization,the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2(LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine(PLL)and negatively charged surface of fibers;this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Electrospun Fibrous Sponges: Principle, Fabrication, and Applications

Electrospun nanofiber materials,with the advantages of large specific surface area,small pore size,high porosity,good channel connectivity,and ease of functional modification,have been widely used in various fields including environmental governance,safety protection,and tissue engineering.With the development of functional fiber materials,the construction of three-dimensional(3D)fiber materials with stable structures has become a critical challenge to expanding application and improving the performance of electrospun fibers.In recent years,researchers have carried out a lot of studies on the 3D reconstruction of electrospun fiber membranes and direct electrospinning of fiber sponges.Specifically,a variety of 3D fibrous sponges were constructed by the 3D reconstruction of electrospun fiber membranes,including embedded hydrogels,3D printing,gas-foaming,and freeze-drying methods.Meanwhile,the direct electrospinning methods of 3D fibrous sponges have also been successfully developed,which are mainly divided into layer-by-layer stacking,liquid-assisted collection,3D template collection,particle leaching,and humidity field regulation.Moreover,the applications of these fibrous sponges in many fields have been explored,such as sound absorption,warmth retention,thermal insulation,air filtration,adsorption/separation,and tissue engineering.These research works provide new ideas and methods for the fabrication of 3D fiber materials.Herein,the electrospinning technology and principle were briefly introduced,the representative progress of 3D fiber sponges in recent years was summarized,and their future development prospected.

Conditioned medium-electrospun fiber biomaterials for skin regeneration

Conditioned medium(CM)contains variety of factors secreted by cells,which directly regulate cellular processes,showing tremendous potential in regenerative medicine.Here,for the first time,we proposed a novel regenerative therapy mediated by biodegradable micro-nano electrospun fibers loaded with highly active conditioned medium of adipose-derived stem cells(ADSC-CM).ADSC-CM was successfully loaded into the nanofibers with biological protection and controllable sustained-release properties by emulsion electrospinning and protein freeze-drying technologies.In vitro,ADSC-CM released by the fibers accelerated the migration rate of fibroblasts;inhibited the over proliferation of fibroblasts by inducing apoptosis and damaging cell membrane;in addition,ADSC-CM inhibited the transformation of fibroblasts into myofibroblasts and suppressed excessive production of extracellular matrix(ECM).In vivo,the application of CM-biomaterials significantly accelerated wound closure and improved regeneration outcome,showing superior pro-regenerative performance.This study pioneered the application of CM-biomaterials in regenerative medicine,and confirmed the practicability and significant biological effects of this innovative biomaterials.