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Abstract

Electrospun nanofiber scaffolds have become vital in biomedical applications due to their high surface area and tunable properties. Chitosan (CS) is widely used, but its rapid degradation limits its effectiveness. This study addresses this limitation by blending CS with polycaprolactone (PCL) and applying genipin cross‐linking to enhance its stability and mechanical properties. Scanning electron microscopy indicated a uniform morphology of the electrospun fibers, and further, the crystallinity of the scaffolds before and after cross‐linking is verified. Fourier‐transform infrared spectroscopy is used to analyze the chemical structure, identifying the presence of trifluoroacetic acid residues in the as‐spun fibers. These residues are successfully eliminated through neutralization and cross‐linking, which are critical for enhancing stability and cell viability in in‐vitro studies. Mechanical testing revealed that cross‐linked CS+PCL scaffolds exhibit a 350% increase in tensile strength compared to pure CS, and zeta potential reaches the favorable for cell development ‐26.27 mV. The cytotoxicity assay results with murine NIH 3T3 fibroblast cells indicate the suitability of CS+PCL scaffolds for targeted tissue engineering and wound healing. This work establishes the potential for fine‐tuning scaffold properties to create stable, functional, and biocompatible substrates for extended biomedical use.

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The enormous potential of electrospun polymer fibers allows for their development in the field of biomaterials for tissue engineering and wound healing. Electrospun fibers based on biodegradable polymers such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are an ideal material for the production of a biocompatible cell scaffold supporting wound closure and skin regeneration. The aim of this research was to create a fibrous PHBV scaffold supporting the 3D environment for anchoring and proliferation of keratinocytes. Moreover, hyaluronic acid (HA) has been used as a coating on PHBV fibers to improve the wound closure processes. ATR-FTIR results indicated the presence of HA in the PHBV scaffolds and UV–Vis analysis confirmed the release of HA from the fibers over 24h test. Importantly, this release of HA increase keratinocyte activity as well their proliferation leading to accelerated wound closure rate in the scratch tests. The designed HA-coated PHBV scaffolds demonstrate the great potential of surface-modified electrospun polymer fibers for wound healing.
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The skin is a complex layer system and the most important barrier between the environment and the organism. In this review, we describe some widespread skin problems, with a focus on eczema, which are affecting more and more people all over the world. Most of treatment methods for atopic dermatitis (AD) are focused on increasing skin moisture and protecting from bacterial infection and external irritation. Topical and transdermal treatments have specific requirements for drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, and efficacy are important for the patches used for skin. Up to today, electrospun fibers are mostly used for wound dressing. Their properties, however, meet the requirements for skin patches for the treatment of AD. Active agents can be incorporated into fibers by blending, coaxial or side‐by‐side electrospinning, and also by physical absorption post‐processing. Drug release from the electrospun membranes is affected by drug and polymer properties and the technique used to combine them into the patch. We describe in detail the in vitro release mechanisms, parameters affecting the drug transport, and their kinetics, including theoretical approaches. In addition, we present the current research on skin patch design. This review summarizes the current extensive know‐how on electrospun fibers as skin drug delivery systems, while underlining the advantages in their prospective use as patches for atopic dermatitis. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies
Article
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 multilayering 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.
Article
In the current study, we fabricated a bilayer wound dressing consisting of an electrospun poly-ε-caprolactone/chitosan (PCL/CS) fibrous mat as the sublayer and a polyurethane (PU) foam coated with ethanolic extract of propolis (EEP) as the top layer. By blending the solutions of PCL and CS, we fabricated an electrospun mat consisting of bead-free and uniform nanofibers with enhanced hydrophilicity, swelling ratio, and degradation properties. To further enhance the mechanical and antibacterial properties, we electrospun the PCL/CS solution on a PU foam coated with EEP to fabricate the PCL/CS-PU/EEP bilayer wound dressing. Furthermore, the PCL/CS-PU/EEP bilayer wound dressing demonstrated enhanced cell compatibility and healing properties through in vitro and in vivo studies. Therefore, the PCL/CS-PU/EEP bilayer wound dressing offers great potential to be used as a wound dressing because of its suitable mechanical properties, swelling profile, antibacterial activity, biocompatibility, and wound healing properties.
Article
Over the last few years, several attempts have been made to replace petrochemical products with renewable and biodegradable components. The most challenging part of this approach is to obtain bio-based materials with properties and functions equivalent to those of synthetic products. Various naturally occurring polymers such as starch, collagen, alginate, cellulose, and chitin represent attractive candidates as they could reduce dependence on synthetic products and consequently positively impact the environment. Chitosan is also a unique bio-based polymer with excellent intrinsic properties. It is known for its anti-bacterial and film-forming properties, has high mechanical strength and good thermal stability. Nanotechnology has also applied chitosan-based materials in its most recent achievements. Therefore, numerous chitosan-based bionanocomposites with improved physical and chemical characteristics have been developed in an eco-friendly and cost-effective approach. This review discusses various sources of chitosan, its properties and methods of modification. Also, this work focuses on diverse preparation techniques of chitosan-based bionanocomposites and their emerging application in various sectors. Additionally, this review sheds light on future research scope with some drawbacks and challenges to motivate the researchers for future outstanding research works.
Article
Negatively charged tissues are ubiquitous in the human body and are associated with a number of common diseases yet remain an outstanding challenge for targeted drug delivery. While the anionic proteoglycans are critical for tissue structure and function, they make tissue matrix dense, conferring a high negative fixed charge density (FCD) that makes drug penetration through the tissue deep zones and drug delivery to resident cells extremely challenging. The high negative FCD of these tissues is now being utilized by taking advantage of electrostatic interactions to create positively charged multi-stage delivery methods that can sequentially penetrate through the full thickness of tissues, create a drug depot and target cells. After decades of work on attempting delivery using strong binding interactions, significant advances have recently been made using weak and reversible electrostatic interactions, a characteristic now considered essential to drug penetration and retention in negatively charged tissues. Here we discuss these advances using examples of negatively charged tissues (cartilage, meniscus, tendons and ligaments, nucleus pulposus, vitreous of eye, mucin, skin), and delve into how each of their structures, tissue matrix compositions and high negative FCDs create barriers to drug entry and explore how charge interactions are being used to overcome these barriers. We review work on tissue targeting cationic peptide and protein-based drug delivery, compare and contrast drug delivery designs, and also present examples of technologies that are entering clinical trials. We also present strategies on further enhancing drug retention within diseased tissues of lower FCD by using synergistic effects of short-range binding interactions like hydrophobic and H-bonds that stabilize long-range charge interactions. As electrostatic interactions are incorporated into design of drug delivery materials and used as a strategy to create properties that are reversible, tunable and dynamic, bio-electroceuticals are becoming an exciting new direction of research and clinical work.
Article
Using Fiber as the based material for photocatalyst particles is favorable for their recovery, thereby avoiding the photocatalyst particles cause secondary pollution to water environment. In this work, the AgBr and Ag3PO4 photocatalyst particles were loaded onto the surface of chitosan fiber (CF) via chelation and in situ anion-exchange method. The photocatalytic results illustrated that the AgBr/Ag3PO4/CF composites displayed the best photocatalytic performance when the mass ratio of Ag3PO4 and AgBr onto the CF was approximately 1:0.15, their degradation rate can reach 98.1% for the methyl orange (MO) solution, this value far exceeded those of pure CF, AgBr/CF composites, and Ag3PO4/CF composites. Besides, the AgBr/Ag3PO4/CF composites also shown excellent durability, after the fifth cycle, they still maintained a decolorization rate of 86.4% for the MO solution, while the Ag3PO4/CF composites maintained a decolorization rate of only 70.7%. Based on these results, we consider that the AgBr/Ag3PO4/CF composites have high practical interest in environmental remediation.
Article
Genipin is an aglycone derived from the geniposide, the most abundant iridoid glucoside constituent of Gardenia jasminoides Ellis. For decades, genipin is the focus of studies as a versatile compound in the treatment of various pathogenic conditions. In particularly, Gardenia jasminoides Ellis has long been used in traditional Chinese medicine for the prevention and treatment of liver disease. Mounting experimental data has proved genipin possesses therapeutic potential for cholestatic, septic, ischemia/reperfusion-triggered acute liver injury, fulminant hepatitis and NAFLD. This critical review is a reflection on the valuable lessons from decades of research regarding pharmacological activities of genipin. Of note, genipin represents choleretic effect by potentiating bilirubin disposal and enhancement of genes in charge of the efflux of a number of organic anions. The anti-inflammatory capability of genipin is mediated by suppression of the production and function of pro-inflammatory cytokines and inflammasome. Moreover, genipin modulates various transcription factor and signal transduction pathway. Genipin appears to trigger the upregulation of several key genes encoding antioxidant and xenobiotic-metabolizing enzymes. Furthermore, the medicinal impact of genipin extends to modulation of regulated cell death, including autophagic cell death, apoptosis, necroptosis and pyroptosis, and modulation of quality of cellular organelle. Another crucial effect of genipin appears to be linked to dual role in targeting uncoupling protein 2 (UCP2). As a typical UCP2-inhibiting compound, genipin could inhibit AMP-activated protein kinase or NF-κB in circumstance. On the contrary, reactive oxygen species production and cellular lipid deposits mediated by genipin through the upregulation of UCP2 is observed in liver steatosis, suggesting the precise role of genipin is disease-specific. Collectively, we comprehensively summarize the mechanisms and pathways associated with the hepatoprotective activity of genipin and discuss potential toxic impact. Notably, our focus is the direct medicinal effect of genipin itself, whereas its utility as a crosslinking agent in tissue engineering is out of scope for the current review. Further studies are therefore required to disentangle these complicated pharmacological properties to confer this natural agent a far greater potency.
Article
In this study, Chitosan/pullulan composite nanofiber fast dissolving oral films (FDOFs) were prepared via electrospinning technology. The ratio of chitosan/pullulan (C/P) had an influence on solution property and nanofiber morphology, with the increase of chitosan, viscosity and conductivity of solutions increased, the morphology obtained by scanning electron microscopy indicated that the diameter of nanofibers decreased initially then increased. The Fourier transform infrared spectra indicated hydrogen bond interactions between chitosan and pullulan molecules. X-ray diffraction analysis proved that electrospinning process decreased the crystallinity of materials. Thermal analysis showed that melting point, degradation temperature and glass transition temperature increased with the addition of chitosan content in the FDOF. Water solubility test proved that the FDOF can dissolve in water completely within 60 s. Finally, in order to prove its practicability in future, a model drug of aspirin was encapsulated in the FDOF successfully.
Article
PVP/chitosan blended nanofibers have been prepared and investigated as adsorbent material for the removal of hexavalent uranium (U(VI)) from aqueous solutions. The nanofibers have been characterized prior and after U(VI) adsorption by SEM and FTIR measurements, and the effect of various parameters such as metal-ion concentration temperature and contact time on the adsorption efficiency has been investigated by batch-type experiments. The material presents increased sorption capacity (q max = (167 ± 25) g kg ⁻¹ at pH 6.0) and increased chemical affinity for U(VI), which is attributed to the fibrous structure of the material and the presence of polar groups (e.g. carbonyl groups) on the blended nanofibers. FTIR spectroscopic measurements indicate the formation of inner sphere complexes between U(VI) and the surface moieties, and thermodynamic and kinetic data reveal a relatively fast (k 1 = 0.01 min ⁻¹ ), entropy-driven process (ΔH o = 56.3 kJ mol ⁻¹ and ΔS o = 293.7 J K ⁻¹ mol ⁻¹ ). Recycling experiments have shown that the material can be used up to four times with less than 10% efficiency loss.
Article
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.
Article
In this paper, nanofibers containing poly(ε-caprolactone) (PCL), chitosan and polypyrrole (PPy) were fabricated using electrospinning to combine advantages of electrospun nanofibers topography with versatile advantages of chitosan and PPy. Various compositions of the PCL/chitosan/PPy polymeric scaffolds were fabricated by electrospinning and were analyzed for their surface topography, hydrophilicity and bioactivity. The results illustrated that chitosan in the scaffold imposed significant advancement in the hydrophilicity of the scaffold as confirmed by a decrease in contact angle up to 66% (123 ± 2.3 for PCL to 41.37 ± 3.51 for PCL/chitosan). The average diameter of the fibers was within the range of 30–180 nm, which influenced by the concentration of the chitosan as the increase up to 30% in chitosan content decreased fiber diameter from 124 nm to 36 nm. In-vitro studies using PC12 cells revealed that the PCL/chitosan/PPy nanofibrous scaffold supports cell attachment, spreading and revealed significant increase in proliferation up to 356% in comparison to Pure PCL and neurite extension of PC12. The results indicated the PCL/chitosan/PPy nanofibrous scaffolds support the adhesion, spreading and proliferation of the PC12 cells. Therefore, this scaffold could serve as promising neural tissue substitutes.
Article
A variety of natural biological tissues (e.g., skin, ligaments, spider silk, blood vessel) exhibit ‘J-shaped’ stress-strain behavior, thereby combining soft, compliant mechanics and large levels of stretchability, with a natural ‘strain-limiting’ mechanism to prevent damage from excessive strain. Synthetic materials with similar stress-strain behaviors have potential utility in many promising applications, such as tissue engineering (to reproduce the nonlinear mechanical properties of real biological tissues) and biomedical devices (to enable natural, comfortable integration of stretchable electronics with biological tissues/organs). Recent advances in this field encompass developments of novel material/structure concepts, fabrication approaches, and unique device applications. This review highlights five representative strategies, including designs that involve open network, wavy and wrinkled morphoologies, helical layouts, kirigami and origami constructs, and textile formats. Discussions focus on the underlying ideas, the fabrication/assembly routes, and the microstructure-property relationships that are essential for optimization of the desired ‘J-shaped’ stress-strain responses. Demonstration applications provide examples of the use of these designs in deformable electronics and biomedical devices that offer soft, compliant mechanics but with inherent robustness against damage from excessive deformation. We conclude with some perspectives on challenges and opportunities for future research.
Article
In this work, Polycaprolactone@Chitosan (PCL@CS) coaxial nanofibers (NFs) were successfully prepared by co-electrospinning technique. Feed rate, solvent ratio 0.6 mL/h and 3:1 was optimized, respectively. Furthermore, coaxial nanofibers were characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimeter (DSC); also contact angle was checked, CS has higher hydrophilicity than PCL@CS and PCL. Silver nanoparticles (AgNPs) were synthesized and immobilized on the coaxial nanofibers. Gram negative Escherichia coli BH5α(E. coli) and Gram positive Staphylococcus aureus (S. aureus) were tested against modified coaxial nanofibers for antibacterial activity, 13 mm inhibition zone was measured against E. coli which was higher than S. aereus.
Article
Unlabelled: The interaction between resident cells and electrospun nanofibers is critical in determining resultant osteoblast proliferation and activity in orthopedic tissue scaffolds. The use of techniques to evaluate cell-nanofiber interactions is critical in understanding scaffold function, with visualization promising unparalleled access to spatial information on such interactions. 3D tomography exploiting focused ion beam (FIB)-scanning electron microscopy (SEM) was used to examine electrospun nanofiber scaffolds to understand the features responsible for (osteoblast-like MC3T3-E1 and UMR106) cell behavior and resultant scaffold function. 3D imaging of cell-nanofiber interactions within a range of electrospun poly(d,l-lactide-co-glycolide acid) (PLGA) nanofiber scaffold architectures indicated a coherent interface between osteoblasts and nanofiber surfaces, promoting osteoblast filopodia formation for successful cell growth. Coherent cell-nanofiber interfaces were demonstrated throughout a randomly organized and aligned nanofiber network. Gene expression of UMR106 cells grown on PLGA fibers did not deviate significantly from those grown on plastic, suggesting maintenance of phenotype. However, considerably lower expression of Ibsp and Alpl on PLGA fibers might indicate that these cells are still in the proliferative phase compared with a more differentiated cell on plastic. This work demonstrates the synergy between designing electrospun tissue scaffolds and providing comprehensive evaluation through high resolution imaging of resultant 3-dimensional cell growth within the scaffold. Statement of significance: Membranes made from electrospun nanofibers are potentially excellent for promoting bone growth for next-generation tissue scaffolds. The effectiveness of an electrospun membrane is shown here using high resolution 3D imaging to visualize the interaction between cells and the nanofibers within the membrane. Nanofibers that are aligned in one direction control cell growth at the surface of the membrane whereas random nanofibers cause cell growth into the membrane. Such observations are important and indicate that lateral cell growth at the membrane surface using aligned nanofibers could be used for rapid tissue repair whereas slower but more extensive tissue production is promoted by membranes containing random nanofibers.
Article
Mismatch of mechanical properties between highly deformable biomedical materials and adjacent native tissue might lead to short and long term health impairment. The capability of implants to deform at the right level, i.e. similar to the macroscopic mechanical response of the surrounding biological materials, is often associated with dissimilar microstructural deformation mechanisms. This mismatch on smaller length scales might lead to micro-injuries, cell damage, inflammation, fibrosis or necrosis. Hence, the mechanical biocompatibility of soft implants depends not only on the properties and composition of the implant material, but also on its organization, distribution and motion at one or several length scales. The challenges related to the analysis and attainment of mechanical biocompatibility are illustrated with two examples: prosthetic meshes for hernia and pelvic repair and electrospun scaffolds for tissue engineering. For these material systems we describe existing methods for characterization and analysis of the non-linear response to uniaxial and multiaxial stress states, its time and history dependence, and the changes in deformation behavior associated with tissue in-growth and material resorption. We discuss the multi-scale deformation behavior of biomaterials and adjacent tissue, and indicate major interdisciplinary questions to be addressed in future research. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
The electrospinning technique allows engineering biomimetic scaffolds within micro to nanoscale range mimicking natural extracellular matrix (ECM). Chitosan (CS) and polycaprolactone (PCL) were dissolved in a modified solvent mixture consisting of formic acid and acetone (3:7) and mixed in different weight ratios to get chitosan-polycaprolactone [CS-PCL] blend solutions. The CS-PCL blend polymer was electrospun in the same solvent system and compared with PCL. The physicochemical characterization of the electrospun fibrous mats was done using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile test, swelling properties, water contact angle (WCA) analysis, surface profilometry and thermo gravimetric analysis (TGA). The CS-PCL fibrous mat showed decreased hydrophobicity. The CS-PCL mats also showed improved swelling property, tensile strength, thermal stability and surface roughness. The cytocompatibility of the CS-PCL and PCL fibrous mats were examined using mouse fibroblast (L-929) cell line by direct contact and cellular activity with extract of materials confirmed non-cytotoxic nature. The potential of CS-PCL and PCL fibrous mats as skin tissue engineering scaffolds were assessed by cell adhesion, viability, proliferation and actin distribution using human keratinocytes (HaCaT) and L-929 cell lines. Results indicate that CS-PCL is a better scaffold for attachment and proliferation of keratinocytes and is a potential material for skin tissue engineering.