Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made with regard to the development of electrospinning methods and engineering of electrospun nanofibers to suit or enable various applications. We aim to provide a comprehensive overview of electrospinning, including the principle, methods, materials, and applications. We begin with a brief introduction to the early history of electrospinning, followed by discussion of its principle and typical apparatus. We then discuss its renaissance over the past two decades as a powerful technology for the production of nanofibers with diversified compositions, structures, and properties. Afterward, we discuss the applications of electrospun nanofibers, including their use as "smart" mats, filtration membranes, catalytic supports, energy harvesting/conversion/storage components, and photonic and electronic devices, as well as biomedical scaffolds. We highlight the most relevant and recent advances related to the applications of electrospun nanofibers by focusing on the most representative examples. We also offer perspectives on the challenges, opportunities, and new directions for future development. At the end, we discuss approaches to the scale-up production of electrospun nanofibers and briefly discuss various types of commercial products based on electrospun nanofibers that have found widespread use in our everyday life.

Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications

In situ tissue regeneration harnesses the body’s regenerative potential to control cell functions for tissue repair. The design of biomaterials for in situ tissue engineering requires precise control over biophysical and biochemical cues to direct endogenous cells to the site of injury. These cues are required to induce regeneration by modulating the extracellular microenvironment or driving cellular reprogramming. In this Review, we outline two biomaterials approaches to control the regenerative capacity of the body for tissue-specific regeneration. The first approach includes the use of bioresponsive materials with an ability to direct endogenous cells, including immune cells and progenitor or stem cells, to facilitate tissue healing, integration and regeneration. The second approach focuses on in situ cellular reprogramming via delivery of transcription factors, RNA-based therapeutics, in vivo gene editing and biomaterials-driven epigenetic transformation. In addition, we highlight tools for engineering the next generation of biomaterials to modulate in situ tissue regeneration. Overall, leveraging the regenerative potential of the human body via engineered biomaterials is a simple and effective approach to replace injured or diseased tissues. In situ tissue regeneration harnesses the body’s regenerative potential for tissue repair using engineered biomaterials. In this Review, we outline various biomaterials approaches to control the body’s regenerative capacity for tissue-specific regeneration by modulating the extracellular microenvironment or driving cellular reprogramming.

Engineered biomaterials for in situ tissue regeneration

The versatile electrospinning technique is recognized as an efficient strategy to deliver active pharmaceutical ingredients and has gained tremendous progress in drug delivery, tissue engineering, cancer therapy, and disease diagnosis. Numerous drug delivery systems fabricated through electrospinning regarding the carrier compositions, drug incorporation techniques, release kinetics, and the subsequent therapeutic efficacy are presented herein. Targeting for distinct applications, the composition of drug carriers vary from natural/synthetic polymers/blends, inorganic materials, and even hybrids. Various drug incorporation approaches through electrospinning are thoroughly discussed with respect to the principles, benefits, and limitations. To meet the various requirements in actual sophisticated in vivo environments and to overcome the limitations of a single carrier system, feasible combinations of multiple drug-inclusion processes via electrospinning could be employed to achieve programmed, multi-staged, or stimuli-triggered release of multiple drugs. The therapeutic efficacy of the designed electrospun drug-eluting systems is further verified in multiple biomedical applications and is comprehensively overviewed, demonstrating promising potential to address a variety of clinical challenges.

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Electrospun Fibrous Architectures for Drug Delivery, Tissue Engineering and Cancer Therapy

Natural fiber systems provide inspirations for artificial fiber spinning and applications. Through a long process of trial and error, great progress has been made in recent years. The natural fiber itself, especially silks, and the formation mechanism are better understood, and some of the essential factors are implemented in artificial spinning methods, benefiting from advanced manufacturing technologies. In addition, fiber-based materials produced via bioinspired spinning methods find an increasingly wide range of biomedical, optoelectronic, and environmental engineering applications. This paper reviews recent developments in the spinning and application of bioinspired fiber systems, introduces natural fiber and spinning processes and artificial spinning methods, and discusses applications of artificial fiber materials. Views on remaining challenges and the perspective on future trends are also proposed.

Spinning and Applications of Bioinspired Fiber Systems.

Scaffolding polymeric biomaterials: Are naturally occurring biological macromolecules more appropriate for tissue engineering?

An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering.

Regenerated silk fibroin (SF) from Bombyx mori silkworm cocoons is a highly regarded natural protein-biomaterial suitable for engineering a variety of biological tissues. Electrospinning offers a unique approach to fiber formation that can readily produce micro- and nano-scale fibers recapitulating the ultrastructure of a native extracellular matrix. However, SF fibers from conventional electrospinning suffer from the problem of poor mechanical properties for load-bearing relevant tissue regeneration applications. In this study, highly aligned high-strength SF fibers were fabricated by a recently emerged stable jet electrospinning (SJES) approach, with the aid of high molecular weight poly(ethylene oxide) (PEO) acting as a fiber-forming ingredient to increase control over the jetting instability during electrospinning. The results showed that 90% of the collected SF/PEO (mass ratio 88 : 12) fiber assembly via SJES oriented unidirectionally with an angle variation of <1° and displayed obvious anisotropic wettability. Mechanically, the as-electrospun highly aligned SF/PEO fibers exhibited a 22.0-fold increase in ultimate tensile strength (50.85 ± 1.13 MPa) and a 49.3-fold increase in Young's modulus (1185.99 ± 164.56 MPa) compared with the randomly oriented SF fibers. A subsequent methanol treatment further remarkably boosted the tensile strength to 73.91 ± 5.15 MPa and Young's modulus to 2426.13 ± 86.67 MPa. The mechanical performance of the SF fibers via SJES was also impressive, even when tested in the wet state. The substantial improvement in the mechanical properties of the electrospun SF fibers is attributed to the SJES-enabled higher molecular orientation and contents of the secondary structure (α-helix and β-pleated sheet), as well as the high degree of fiber alignment. Moreover, biological tests verified that these SF-based fibrous scaffolds supported the induced pluripotent stem cell derived mesenchymal stem cells to adhere, migrate and grow in a manner of orienting along the fiber axis. We speculate that these high-performance biomimicking SF fibers might give rise to improved efficacy while being utilized to architecturally regenerate anisotropic load-bearing tissues (e.g., tendon, ligament, and blood vessel).

Fabrication of high performance silk fibroin fibers via stable jet electrospinning for potential use in anisotropic tissue regeneration.

Electrospun natural-synthetic composite nanofibers, which possess favorable biological and mechanical properties, have gained widespread attention in tissue engineering. However, the development of biomimetic nanofibers of hybrids remains a huge challenge due to phase separation of the polymer blends. Here, aqueous sodium hydroxide (NaOH) solution is proposed to modulate the miscibility of a representative natural-synthetic hybrid of gelatin (GT) and polycaprolactone (PCL) for electrospinning homogeneous composite nanofibers. Alkali-doped GT/PCL solutions and nanofibers examined at macroscopic, microscopic, and internal molecular levels demonstrate appropriate miscibility of GT and PCL after introducing the alkali dopant. Particularly, homogeneous GT/PCL nanofibers with smooth surface and uniform diameter are obtained when aqueous NaOH solution with a concentration of 10 m is used. The fibers become more hydrophilic and possess improved mechanical properties both in dry and wet conditions. Moreover, biocompatibility experiments show that stem cells adhere to and proliferate better on the alkali-modified nanofibers than the untreated one. This study provides a facile and effective approach to solve the phase separation issue of the synthetic-natural hybrid GT/PCL and establishes a correlation of compositionally and morphologically homogeneous composite nanofibers with respect to cell responses.

Alkali‐Mediated Miscibility of Gelatin/Polycaprolactone for Electrospinning Homogeneous Composite Nanofibers for Tissue Scaffolding

In this work, an Au/GaN photoelectrode was prepared by sputtering a 30.0-nm–thick gold film on an n-type gallium nitride (GaN) surface. Guanine (G) was used as a hole trap in photoinduced charge separation due to its lowest oxidation potential and because it could be easily oxidized among the five common nucleobases. Guanosine-rich DNA sequences can form stable secondary structures known as G-quadruplexes. The efficiency of hole transport was significantly improved after G-quadruplexes formation. The thrombin aptamer rich in guanine could be modified on the electrode surface through Au–S bonds, forming stable G-quadruplexes in the presence of target thrombin. Due to the presence of the G-quadruplexes, the electron-hole recombination rate of the system decreased and the photocurrent increased. Under optimized conditions, high specificity, selectivity, and linearity could be achieved in the concentration range of 0.100–10.0 nm, and the limit of detection was approximately 20.0 pM. Thus, the detection results of human serum thrombin were satisfactory. • The guanine-rich DNA strand trap photogenerated holes of the GaN photoanode resulted in an increase in photocurrent. • G-Quadruplex is more easily oxidized because π stacked guanine quartets promote rapid hole transfer. • A label-free thrombin PEC aptasensor was developed. 

Huilan Zhang

Papers

An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering.

Fabrication of high performance silk fibroin fibers via stable jet electrospinning for potential use in anisotropic tissue regeneration.

Alkali‐Mediated Miscibility of Gelatin/Polycaprolactone for Electrospinning Homogeneous Composite Nanofibers for Tissue Scaffolding

A label-free thrombin photoelectrochemical aptasensor based on structure-switching in G-quadruplexes