Tunable 3D Nanofiber Architecture of Polycaprolactone by Divergence Electrospinning for Potential Tissue Engineering Applications

The creation of biomimetic cell environments with micro and nanoscale topographical features resembling native tissues is critical for tissue engineering. To address this challenge, this study focuses on an innovative electrospinning strategy that adopts a symmetrically divergent electric field to induce rapid self-assembly of aligned polycaprolactone(PCL) nanofibers into a centimeter-scale architecture between separately grounded bevels. The 3D microstructures of the nanofiber scaffolds were characterized through a series of sectioning in both vertical and horizontal directions. PCL/collagen(type I)nanofiber scaffolds with different density gradients were incorporated in sodium alginate hydrogels and subjected to elemental analysis. Human fibroblasts were seeded onto the scaffolds and cultured for 7 days. Our studies showed that the inclination angle of the collector had significant effects on nanofiber attributes, including the mean diameter, density gradient, and alignment gradient. The fiber density and alignment at the peripheral area of the 45°-collector decreased by 21% and 55%, respectively, along the z-axis,while those of the 60°-collector decreased by 71% and 60%, respectively. By altering the geometry of the conductive areas on the collecting bevels, polyhedral and cylindrical scaffolds composed of aligned fibers were directly fabricated. By using a four-bevel collector, the nanofibers formed a matrix of microgrids with a density of 11%. The gradient of nitrogen-to-carbon ratio in the scaffold-incorporated hydrogel was consistent with the nanofiber density gradient. The scaffolds provided biophysical stimuli to facilitate cell adhesion, proliferation, and morphogenesis in 3D.

Preparation of polypyrrole-embedded electrospun poly(lactic acid) nanofibrous scaffolds for nerve tissue engineering

Polypyrrole （PPy） is a biocompatible polymer with good conductivity. Studies combining PPy with electrospinning have been reported; however, the associated decrease in PPy conductivity has not yet been resolved. We embedded PPy into poly（lactic acid） （PLA） nanofibers via electrospinning and fabricated a PLA/PPy nanofibrous scaffold containing 15% PPy with sustained conductivity and aligned topog- raphy, qhere was good biocompatibility between the scaffold and human umbilical cord mesenchymal stem cells as well as Schwann cells. Additionally, the direction of cell elongation on the scaffold was parallel to the direction of fibers. Our findings suggest that the aligned PLA/PPy nanofibrous scaffold is a promising biomaterial for peripheral nerve regeneration.

Fabrication of hierarchical polycaprolactone/gel scaffolds via combined 3D bioprinting and electrospinning for tissue engineering

It is a severe challenge to construct 3D scaf- folds which hold controllable pore structure and similar morphology of the natural extracellular matrix （ECM）. In this study, a compound technology is proposed by com- bining the 3D bioprinting and electrospinning process to fabricate 3D scaffolds, which are composed by orthogonal array gel microfibers in a grid-like arrangement and inter- calated by a nonwoven structure with randomly distributed polycaprolactone （PCL） nanofibers. Human adipose- derived stem cells （hASCs） are seeded on the hierarchical scaffold and cultured 21 d for in vitro study. The results of cells culturing show that the microfibers structure with controlled pores can allow the easy entrance of cells and the efficient diffusion of nutrients, and the nanofiber webs layered in the scaffold can significantly improve initial cell attachment and proliferation. The present work demon- strates that the hierarchical PCL/gel scaffolds consisting of controllable 3D architecture with interconnected pores and biomimetic nanofiber structures resembling the ECM can be designed and fabricated by the combination of 3D bioprinting and electrospinning to improve biological per- formance in tissue engineering applications.

Electrospinning nanofiber scaffolds for soft and hard tissue regeneration

Tissue engineering is an interdisciplinary field that integrates medical,biological,and engineering expertise to restore or regenerate the functionality of healthy tissues and organs.The three fundamental pillars of tissue engineering are scaffolds,cells,and biomolecules.Electrospun nanofibers have been successfully used as scaffolds for a variety of tissue engineering applications because they are biomimetic of the natural,fibrous extracellular matrix(ECM)and contain a three-dimensional(3D)network of interconnected pores.In this review,we provide an overview of the electrospinning process,its principles,and the application of the resultant electrospun nanofibers for tissue engineering.We first briefly introduce the electrospinning process and then cover its principles and standard equipment for biomaterial fabrication.Next,we highlight the most important and recent advances related to the applications of electrospun nanofibers in tissue engineering,including skin,blood vessels,nerves,bone,cartilage,and tendon/ligament applications.Finally,we conclude with current advancements in the fabrication of electrospun nanofiber scaffolds and their biomedical applications in emerging areas.

Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration

Repairing large-area soft tissue defects caused by traumas is a major surgical challenge.Developing multifunctional scaffolds with suitable scalability and favorable cellular response is crucial for soft tissue regeneration.In this study,we developed an orthogonally woven three-dimensional(3D)nanofiber scaffold combining electrospinning,weaving,and modified gas-foaming technology.The developed orthogonally woven 3D nanofiber scaffold had a modular design and controlled fiber alignment.In vitro,the orthogonally woven 3D nanofiber scaffold exhibited adjustable mechanical properties,good cell compatibility,and easy drug loading.In vivo,for one thing,the implantation of an orthogonally woven 3D nanofiber scaffold in a full abdominal wall defect model demonstrated that extensive granulation tissue formation with enough mechanical strength could promote recovery of abdominal wall defects while reducing intestinal adhesion.Another result of diabetic wound repair experiments suggested that orthogonally woven 3D nanofiber scaffolds had a higher wound healing ratio,granulation tissue formation,collagen deposition,and re-epithelialization.Taken together,this novel orthogonally woven 3D nanofiber scaffold may provide a promising and effective approach for optimal soft tissue regeneration.

Recent Advancements on Three‑Dimensional Electrospun Nanofiber Scaffolds for Tissue Engineering

Electrospinning is widely accepted as a technique for the fabrication of nanofibrous three-dimensional(3D)scaffolds which mimic extracellular matrix(ECM)microenvironment for tissue engineering(TE).Unlike normal densely-packed two-dimensional(2D)nanofibrous membranes,3D electrospun nanofiber scaffolds are dedicated to more precise spatial control,endowing the scaffolds with a sufficient porosity and 3D environment similar to the in vivo settings as well as optimizing the properties,including injectability,compressibility,and bioactivity.Moreover,the 3D morphology regulates cellular interaction and mediates growth,migration,and differentiation of cell for matrix remodeling.The variation among scaffold structures,functions and applications depends on the selection of electrospinning materials and methods as well as on the post-processing of electrospun scaffolds.This review summarizes the recent new forms for building electrospun 3D nanofiber scaffolds for TE applications.A variety of approaches aimed at the fabrication of 3D electrospun scaffolds,such as multilay-ering electrospinning,sacrificial agent electrospinning,wet electrospinning,ultrasound-enhanced electrospinning as well as post-processing techniques,including gas foaming,ultrasonication,short fiber assembly,3D printing,electrospraying,and so on are discussed,along with their advantages,limitations and applications.Meanwhile,the current challenges and prospects of 3D electrospun scaffolds are rationally discussed,providing an insight into developing the vibrant fields of biomedicine.

Electrospinning nanofibers to ID,2D,and 3D scaffolds and their biomedical applications

Electrospinning is a popular and effective method of producing porous nanofibers with a large surface area,superior physical and chemical properties,and a controllable pore size.Owing to these properties,electrospun nanofibers can mimic the extracellular matrix and some human tissue structures,based on the fiber configuration.Consequently,the application of electrospun nanofibers as biomaterials,varying from two-dimensional(2D)wound dressings to three-dimensional(3D)tissue engineering scaffolds,has increased rapidly in recent years.Nanofibers can either be uniform fiber strands or coaxial drug carriers,and their overall structure varies from random mesh-like mats to aligned or gradient scaffolds.In addition,the pore size of the fibers can be adjusted or the fibers can be loaded with disparate medicines to provide different functions.This review discusses the various structures and applications of 2D fiber mats and 3D nanofibrous scaffolds made up of different one-dimensional(1D)fibers in tissue engineering.In particular,we focus on the improvements made in recent years,especially in the fields of wound healing,angiogenesis,and tissue regeneration.

Fabrication of a Novel Hybrid Scaffold for Tissue Engineered Heart Valve

The aim of this study was to fabricate biomatrix/polymer hybrid scaffolds using an electrospinning technique. Then tissue engineered heart valves were engineered by seeding mesenchymal stromal cells （MSCs） onto the scaffolds. The effects of the hybrid scaffolds on the proliferation of seed cells, formation of extracellular matrix and mechanical properties of tissue engineered heart valves were investigated. MSCs were obtained from rats. Porcine aortic heart valves were decellularized, coated with poly（3-hydroxybutyrate-co-4-hydroxybutyrate） using an electrospinning technique, and reseeded and cultured over a time period of 14 days. In control group, the decellularized valve scaffolds were reseeded and cultured over an equivalent time period. Specimens of each group were examined histologically （hematoxylin-eosin [HE] staining, immunohistostaining, and scanning electron microscopy）, biochemically （DNA and 4-hydroxyproline） and mechanically. The results showed that recellularization was comparable to the specimens of hybrid scaffolds and controls. The specimens of hybrid scaffolds and controls revealed comparable amounts of cell mass and 4-hydroxyproline （P〉0.05）. However, the specimens of hybrid scaffolds showed a significant increase in mechanical strength, compared to the controls （P〈0.05）. This study demonstrated the superiority of the hybrid scaffolds to increase the mechanical strength of tissue engineered heart valves. And compared to the decellularized valve scaffolds, the hybrid scaffolds showed similar effects on the proliferation of MSCs and formation of extracellular matrix. It was believed that the hybrid scaffolds could be used for the construction of tissue engineered heart valves.

Fabrication and characterization of Antheraea pernyi silk fibroin-blended P（LLA-CL） nanofibrous scaffolds for peripheral nerve tissue engineering

Electrospun nanofibers have gained widespreading interest for tissue engineering application. In the present study, ApF/P（LLA-CL） nanofibrous scaffolds were fabricated via electrospinning. The feasibility of the material as tissue engineering nerve scaffold was investigated in vitro. The average diameter increased with decreasing the blend ratio of ApF to P（LLA-CL）. Characterization of 13C NMR and FTIR clarified that there is no obvious chemical bond reaction between ApF and P（LLA-CL）. The tensile strength and elongation at break increased with the content increase of P（LLA-CL）. The surface hydrophilic property of nanofibrous scaffolds enhanced with the increased content of ApF. Cell viability studies with Schwann cells demonstrated that ApFIP（LLA-CL） blended nanofibrous scaffolds significantly promoted cell growth as compare to P（LLA-CL）, especially when the weight ratio of ApF to P（LLA-CL） was 25：75. The present work provides a basis for further studies of this novel nanofibrous material （ApF/P（LLA-CL）） in peripheral nerve tissue repair or regeneration.

Fabrication of scaffolds in tissue engineering： A review

Tissue engineering （TE） is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

Resorbable polymer electrospun nanofibers:History,shapes and application for tissue engineering

Resorbable polymer electrospun nanofiber-based materials/devices have high surface-to-volume ratio and often have a porous structure with excellent pore interconnectivity,which are suitable for growth and development of different types of cells.Due to the huge advantages of both resorbable polymers and electrospun nano fibers,re sorbable polymer electrospun nanofibers(RPENs)have been widely applied in the field of tissue engineering.In this paper,we will mainly introduce RPENs for tissue engineering.Firstly,the electrospinning technique and electrospun nanofiber architectures are briefly introduced.Secondly,the application of RPENs in the field of tissue engineering is mainly reviewed.Finally,the advantages and disadvantages of RPENs for tissue engineering are discussed.This review will provide a comprehensive guide to apply resorbable polymer electrospun nanofibers for tissue engineering.

Anisotropy Properties of Tissues: A Basis for Fabrication of Biomimetic Anisotropic Scaffolds for Tissue Engineering

Tissue engineering has been a subject of extensive scientific exploration in the last two decades making gradual inroads into clinical studies as well.Along with regenerative cells and growth factors,biomaterial scaffolds are integral to the development of a tissue engi neered construct.It is now appreciated that scaffolds should mimic the target tissue properties intimately in order to provide a micro-environment milieu that allows the seeded cells to differentiate into the desired tissue.Even from a structural viewpoint,mismatch between scaffold and native matrix properties can cause cell necrosis through mechanisms such as stress shielding.One of the key prop erties of most body tissues is that they exhib社anisotropy.However,most fabrication methods generate isotropic scaffolds and require specific modifications to produce anisotropic scaffolds.In the last decade,the advent of additive manufacturing and bioprinting has provided facile tools to fabricate scaffolds with desired anisotropy.On the other hand,a biomimetic scaffold can be designed only when target tissue anisotropy is well known to the tissue engineer.This review presents an overview of the anisotropic properties of different tissues,which will be critical for developing biomimetic engineered constructs.The traditional anatomical records do not adequately present these properties from the perspective of designing tissue engineering scaffolds.Subsequently,present state-of-the art in devel opment of anisotropic scaffolds as well as tissue constructs using different conventional and emerging fabrication techniques is discussed.It is expected that the readers will obtain a comprehensive reference on the research area by examining these two aspects juxtaposed to each other and gain key trends for fabrication of anisotropic scaffolds,plausibly with improved regenerative outcomes.

Effect of incorporating Elaeagnus angustifolia extract in PCL-PEG-PCL nanofibers for bone tissue engineering

Plants have been used for medicinal purposes for thousands of years but they are still finding new uses in modem times. For example, Elaeagnus angustifolia (EA) is a medicinal herb with antinociceptive, anti-inflammatory, antibacterial and antioxidant properties and it is widely used in the treatment of rheumatoid arthritis and osteoarthritis. EA extract was loaded onto poly(ε-caprolactone)- poly(ethylene glycol)-poly(ε-caprolactone)(PCLPEG-PCL/EA) nanofibers and their potential applications for bone tissue engineering were studied. The morphology and chemical properties of the fibers were evaluated using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, contact angle measurements and mechanical tests. All the samples had bead-free morphologies with average diameters ranging from 100 to 200 nm. The response of human cells to the PCL-PEGPCL/ EA nanofibers was evaluated using human dental pulp stem cells (hDPSCs). The hDPSCs had better adhesion and proliferation capacity on the EA loaded nanofibers than on the pristine PCL-PEG?PCL nanofibers. An alizarin red S assay and the alkaline phosphatase activity confirmed that the nanofibrous scaffolds induced osteoblastic performance in the hDPSCs. The quantitative real time polymerase chain reaction results confirmed that the EA loaded nanofibrous scaffolds had significantly upregulated gene expression correlating to osteogenic differentiation. These results suggest that PCL-PEG-PCL/ EA nanofibers might have potential applications for bone tissue engineering.

Electrospun nanofiber/hydrogel composite materials and their tissue engineering applications

Electrospun nanofiber/hydrogel composites combine the excellent biochemical properties of hydrogel with the biomimetic nature of electrospun fibers,and have attracted widespread attention in the last few years.Besides,nanofiber/hydrogel composites with tunable mechanical properties can mimic the microstructure of extracellular matrix(ECM)of various tissues and the microenvironment of different cells.These features enable electrospun fiber/hydrogel composites have uniquely advantageous for tissue repair.However,a comprehensive review of electrospun fiber/hydrogel composites as tissue engineering scaffolds is still lacking.Thus,this article systematically reviewed the preparation of electrospun fiber/hydrogel composites and their application in tissue engineering.First,the preparation strategies of electrospun fiber/hydrogel composites are classified and discussed.Second,the application of electrospun fiber/hydrogel-based scaffolds in tissue engineering,involving skin,blood vessel,nerve,bone and other tissue engineering,are summarized.Finally,future research directions for functional electrospun fiber/hydrogel scaffold materials are proposed.

A novel electrospinning method for self-assembled tree-like fibrous scaffolds:Microenvironment-associated regulation of MSC behavior and bone regeneration

Numerous studies highlight advantages of electrospun scaffolds in bone tissue engineering,in which cellular behavior is tightly affected by fiber topographical cues of scaffolds.However,the classic electrospinning setup limits a desired presentation of biomimetic fibrous microenvironments that sense mechanosignaling and regulate stem cell behavior.The aims of this study were to fabricate advanced asspun scaffolds presenting tree-like microfiber/nanonet networks and to evaluate their regulatory potentials on behavior of human mesenchymal stem cells(h MSCs)and bone regeneration.Here we developed a novel electrospinning setup that allowed the presentation of patterned Trunk microfibers(TMF)and/or branched nanonet fibers(BNn Fs)in biomimetic fibrous scaffolds.As the cellular mechanisms,anisotropichierarchical topography of TMF controlled behavior of h MSCs through focal adhesion formation and Yesassociated protein(YAP)induction,whereas BNn F disturbed such mechanosensing responses in the cells.The fiber microenvironment-related expression and nuclear localization of YAP were.also correlated with the potentials of as-spun scaffolds to enhance osteogenic differentiation of the h MSCs and alveolar bone defect healing in an animal model.Collectively,this study provides an advanced approach of the modified electrospinning setup for presentation of biomimetic fibrillar microenvironments in as-spun scaffolds along with their application in stem cell behavior regulation and regenerative tissue engineering.

Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds

Electrospinning is a versatile strategy for creating nanofiber materials with various structures,which has broad application for a myriad of areas ranging from tissue engineering,energy harvesting,filtration and has become one of the most important academic and technical activities in the field of material science in recent years.In addition to playing a significant role in the construction of two-dimensional(2D)nanomaterials,electrospinning holds great promise as a robust method for producing three-dimensional(3D)aerogels and scaffolds.This article reviews and summarizes the recent advanced methods for fabricating electrospun three-dimensional nanofiber aerogels and scaffolds,including gas foaming,direct electrospinning of 3D nanofibrous scaffold,short nanofibers assembling into 3D aerogels/scaffolds,3D printing,electrospray,origami and cell sheet engineering,centrifugal electrospinning,and other methods.Besides,intriguing formation process,crosslinking pathway,properties,and applications of 3D aerogels and scaffolds are also introduced.Taken together,these aerogels and scaffolds with various excellent features present tremendous potential in various fields.

Characterization on Modification and Biocompatibility of PCL Scaffold Prepared with Near-field Direct-writing Melt Electrospinning

In this study,orthogonal experiments were designed to explore the optimal process parameters for preparing polycaprolactone(PCL)scaffolds by the near-field direct-writing melt electrospinning(NFDWMES)technology.Based on the optimal process parameters,the PCL scaffolds with different thicknesses,gaps and structures were manufactured and the corresponding hydrophilicities were characterized.The PCL scaffolds were modified by chitosan(CS)and hyaluronic acid(HA)to improve biocompatibility and hydrophilicity.Both Fourier transform infrared spectroscopy(FTIR)analysis and antibacterial experimental results show that the chitosan and hyaluronic acid adhere to the surface of PCL scaffolds,suggesting that the modification plays a positive role in biocompatibility and antibacterial effect.The PCL scaffolds were then employed as a carrier to culture cells.The morphology and distribution of the cells observed by a fluorescence microscope demonstrate that the modified PCL scaffolds have good biocompatibility,and the porous structure of the scaffolds is conducive to adhesion and deep growth of cells.

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes.However,the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging.This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions.The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional(2D).The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices,which were arrayed.These 2D slices with each layer of a defined pattern were laser cut,and then successfully assembled with varying thicknesses of 100μm or 200μm.It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions,where the clinically relevant sizes ranging from a simple cube of 20 mm dimension,to a more complex,50 mm-tall human ears were created.In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure.The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice,where a range of hole diameters from 200μm to 500μm were laser cut in an array where cell confluence values of at least 85%were found at three weeks.Cells were also seeded onto a simpler stacked construct,albeit made with micromachined poly fibre mesh,where cells can be found to migrate through the stack better with collagen as bioadhesives.This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

Electrospun Poly(p-dioxanone)/Poly(ester-urethane)ureas Composite Nanofibers for Potential Heart Valve Tissue Reconstruction

Electrospun nanofibrous mats represent a new generation of medical textiles with promising applications in heart valve tissue reconstruction. It is important for biomaterials to mimic the biological and mechanical microenvironment of native extracellular matrix(ECM). However, the major challenges are still remaining for current biomedical materials, including appropriate mechanical properties,biocompatibility, and hemocompatibility. In the present work, the novel composite nanofibrous mats of poly(p-dioxanone)(PDO) and poly(ester-urethane)ureas(PEUU) are fabricated by electrospinning system. The optimal combination ratio of PDO to PEUU may balance the mechanical properties and cellular compatibility to match the newly formed tissue. In PDO/PEUU composite nanofibrous mats, PEUU can provide the biomimetic elastomeric behavior, and PDO could endow the excellent biocompatibility. In comparison to nanofibrous mat of neat PDO, the composite showed significantly improved mechanical properties, with 5-fold higher initial elongation at break.Furthermore, human umbilical vein endothelial cells(HUVECs) were cultured on the composite to evaluate its ability to rapidly endothelialize as heart valve tissue engineering. The results revealed that PDO/PEUU composite nanofibrous mats could promote cell adhesion and proliferation, especially for the ratio of 60/40. Overall, PDO/PEUU composite nanofibrous mats(60/40) show the excellent mechanical properties, appropriate biocompatibility and hemocompatibility which meet the necessary norm for tissue engineering and may be suitable for potential heart valve tissue reconstruction.

Heparin/Growth Factors‑Immobilized Aligned Electrospun Nanofibers Promote Nerve Regeneration in Polycaprolactone/Gelatin‑Based Nerve Guidance Conduits

Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require extracellular matrix(ECM)-like features to better mimic the in vivo microenvironment.Consequently,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial NGCs.Heparin was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)nanofibers.Thereafter,basic fibroblast growth factor(bFGF)and nerve growth factor(NGF)were preferentially immobilized on heparinized nanofibers;the immobilization efficiency of GFs was found to be 50%with respect to(w.r.t.)their initial loaded amounts.The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention(~10%w.r.t the initial loaded amount)and bioactivity of NGF for up to 5 days.The permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate membranes.The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term(1 week)and long-term(1-month).The NGCs displayed good structural stability and biocompatibility in vivo.The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs.Taken together;these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.