The development of three-dimensional polymeric systems capable of mimicking the extracellular matrix is critical for advancing tissue engineering. To achieve these objectives, three-dimensional fibrous scaffolds with "clay"-like properties were successfully developed by coaxially electrospinning polystyrene (PS) and poly(ε-caprolactone) (PCL) and selective leaching. As PS is known to be nonbiodegradable and vulnerable to mechanical stress, PS layers present at the outer surface were removed using a "selective leaching" process. The fibrous PCL scaffolds that remained after the leaching step exhibited highly advantageous characteristics as a tissue engineering scaffold, including moldability (i.e., clay-like), flexibility, and three-dimensional structure (i.e., cotton-like). More so, the "clay-like" PCL fibrous scaffolds could be shaped into any desired form, and the microenvironment within the clay scaffolds was highly favorable for cell expansion both in vitro and in vivo. These "electrospun-clay" scaffolds overcome the current limitations of conventional electrospun, sheet-like scaffolds, which are structurally inflexible. Therefore, this work extends the scope of electrospun fibrous scaffolds toward a variety of tissue engineering applications.

The integration of gene delivery technologies with electrospun nanofibers is a versatile strategy to increase the potential of gene therapy as a key platform technology that can be readily utilized for numerous biomedical applications, including cancer therapy, stem cell therapy, and tissue engineering. As a spatial template for gene delivery, electrospun nanofibers possess highly advantageous characteristics, such as their ease of production, their ECM-analogue nature, the broad range of choices for materials, the feasibility of producing structures with varied physical and chemical properties, and their large surface-to-volume ratios. Thus, electrospun fiber-mediated gene delivery exhibits a great capacity to modulate the spatial and temporal release kinetics of gene vectors and enhance gene delivery efficiency. This review discusses the powerful characteristics of electrospun nanofibers, which can function as spatial interfaces capable of promoting controlled and efficient gene delivery.Electronic supplementary materialThe online version of this article (doi:10.1186/1754-1611-8-30) contains supplementary material, which is available to authorized users.

Designing biomaterial systems that can mimic fibrous, natural extracellular matrix is crucial for enhancing the efficacy of various therapeutic tools. Herein, a smart technology of three-dimensional electrospun fibers that can be injected in a minimally invasive manner was developed. Open surgery is currently the only route of administration of conventional electrospun fibers into the body. Coordinating electrospun fibers with a lubricating hydrogel produced fibrous constructs referred to as slidable, injectable, and gel-like (SLIDING) fibers. These SLIDING fibers could pass smoothly through a catheter and fill any cavity while maintaining their fibrous morphology. Their injectable features were derived from their distinctive rheological characteristics, which were presumably caused by the combinatorial effects of mobile electrospun fibers and lubricating hydrogels. The resulting injectable fibers fostered a highly favorable environment for human neural stem cell (hNSC) proliferation and neurosphere formation within the fibrous structures without compromising hNSC viability. SLIDING fibers demonstrated superior performance as cell carriers in animal stroke models subjected to the middle cerebral artery occlusion (MCAO) stroke model. In this model, SLIDING fiber application extended the survival rate of administered hNSCs by blocking microglial infiltration at the early, acute inflammatory stage. The development of SLIDING fibers will increase the clinical significance of fiber-based scaffolds in many biomedical fields and will broaden their applicability.

Electrospun fibrous mats have emerged as powerful tissue engineering scaffolds capable of providing highly effective and versatile physical guidance, mimicking the extracellular environment. However, electrospinning typically produces a sheet-like structure, which is a major limitation associated with current electrospinning technologies. To address this challenge, highly porous, volumetric hydrogel-hybrid fibrous scaffolds were fabricated by one Taylor cone-based side-by-side dual electrospinning of poly (ε-caprolactone) (PCL) and poly (vinyl pyrrolidone) (PVP), which possess distinct properties (i.e., hydrophobic and hydrogel properties, respectively). Immersion of the resulting scaffolds in water induced spatial tortuosity of the hydrogel PVP fibers while maintaining their aligned fibrous structures in parallel with the PCL fibers. The resulting conformational changes in the entire bicomponent fibers upon immersion in water led to volumetric expansion of the fibrous scaffolds. The spatial fiber tortuosity significantly increased the pore volumes of electrospun fibrous mats and dramatically promoted cellular infiltration into the scaffold interior both in vitro and in vivo. Harmonizing the flexible PCL fibers with the soft PVP-hydrogel layers produced highly ductile fibrous structures that could mechanically resist cellular contractile forces upon in vivo implantation. This facile dual electrospinning followed by the spatial fiber tortuosity for fabricating three-dimensional hydrogel-hybrid fibrous scaffolds will extend the use of electrospun fibers toward various tissue engineering applications.

Surface hydrophobicity has served as a core means for governing the spatial behaviors of numerous substances depending on their affinities to oil or aqueous phases. Exploiting systems that can maximize hydrophobic features contributes to the development of versatile supports capable of spatially separating, guiding, or protecting target materials in defined manners. Herein, superhydrophobic, reversibly elastic, moldable, and electrospun (SupREME) fibers, which exhibit multimodal functions for arranging spatial responses of substances with distinct affinities to oil phases, are fabricated by coaxially electrospinning polysulfone and poly(glycerol sebacate) (PGS), followed by a thermal process. The exterior PSF layers enable volumetric expansion of the fibers, further reinforcing the overall superhydrophobicity (contact angles >150°). The elastic core PGS networks confer reversibly compressible properties (>100 cycles) to the fibers, ultimately enhancing their hydrophobic performance and extending their durability. The SupREME fibers demonstrate superiorities as absorbents for selectively separating oilbased substances, sealants for blocking the leakage of aqueous fluids, and adjuvants for temporarily enhancing the local residence of drugs by repelling ambient fluidic environments. The SupREME fibers can be versatile platforms in many applications that require the spatial regulation of specific substances with affinities to oil or water phases, ranging from environmental industries to medical fields.

Controlled release of biosuprastructures, such as viruses, from surfaces has been a challenging task in providing efficient ex vivo gene delivery. Conventional controlled viral release approaches have demonstrated low viral immobilization and burst release, inhibiting delivery efficiency. Here, a highly powerful substrate-mediated viral delivery system was designed by combining two key components that have demonstrated great potential in the fields of gene therapy and surface chemistry, respectively: adeno-associated viral (AAV) vectors and adhesive catecholamine surfaces. The introduction of a nanoscale thin coating of catecholamines, poly(norepinephrine) (pNE) or poly(dopamine) (pDA) to provide AAV adhesion followed by human neural stem cell (hNSC) culture on sticky solid surfaces exhibited unprecedented results: approximately 90% loading vs 25% (AAV_bare surface), no burst release, sustained release at constant rates, approximately 70% infection vs 20% (AAV_bare surface), and rapid internalization. Importantly, the sticky catecholamine-mediated AAV delivery system successfully induced a physiological response from hNSCs, cellular proliferation by a single-shot of AAV encoding fibroblast growth factor-2 (FGF-2), which is typically achieved by multiple treatments with expensive FGF-2 proteins. By combining the adhesive material-independent surface functionalization characters of pNE and pDA, this new sticky "delivering-from" gene delivery platform will make a significant contribution to numerous fields, including tissue engineering, gene therapy, and stem cell therapy.

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The establishment of versatile biomaterial interfaces that can facilitate cellular adhesion is crucial for elucidating the cellular processes that occur on biomaterial surfaces. Furthermore, biomaterial interfaces can provide physical or chemical cues that are capable of stimulating cellular behaviors by regulating intracellular signaling cascades. Herein, a method of creating a biomimetic functional biointerface was introduced to enhance human neural stem cell (hNSC) adhesion. The hNSC-compatible biointerface was prepared by the oxidative polymerization of the neurotransmitter norepinephrine, which generates a nanoscale organic thin layer, termed poly(norepinephrine) (pNE). Due to its adhesive property, pNE resulted in an adherent layer on various substrates, and pNE-coated biointerfaces provided a highly favorable microenvironment for hNSCs, with no observed cytotoxicity. Only a 2-hour incubation of hNSCs was required to firmly attach the stem cells, regardless of the type of substrate. Importantly, the adhesive properties of pNE interfaces led to micropatterns of cellular attachment, thereby demonstrating the ability of the interface to organize the stem cells. This highly facile surface-modification method using a biomimetic pNE thin layer can be applied to a number of suitable materials that were previously not compatible with hNSC technology.