Biodegradable ultrafine fibers with core–sheath structures for protein delivery and its optimization

This study was aimed to design core–sheath‐structured polymeric fibers for protein delivery through emulsion electrospinning to enhance the encapsulation efficiency (EE), structural integrity, and activity retention, and to achieve controllable protein release. Integral core–sheath structure was achieved for electrospun fibers with lysozyme loading efficiency of 93.3% and the specific activity retention (SAR) of 64.6%, while the surface protein content (SP) was as low as 4.2%. The emulsion components were optimized to minimize the burst release and extend the release period, and the release profiles were found to be closely related with the fiber characteristics such as the SPs. An initial burst release as low as 6.2% followed by gradual release for 33 days was indicated from poly(ethylene glycol)‐poly(DL ‐lactide) (PELA) fibers. The gradual protein release was determined by a competition of fiber collapse leading to accelerated release and fiber fusion leading to decelerated release. Dependent on the matrix polymer and protein encapsulated, the degradation behaviors of the fiber matrices were correlated with the release rate and the effective lifetime of the drug release. The core–sheath‐structured ultrafine fibers could protect the structural integrity and bioactivity of encapsulated lysozyme, and an increase in the protective effect was demonstrated for fibers prepared from PELA matrix. Copyright © 2010 John Wiley & Sons, Ltd.     

Electrospun Polymeric Fibers Decorated with Silk Microcapsules via Encapsulation and Surface Immobilization for Drug Delivery

Hollow polymer microcapsules as drug carriers have the advantages of drug protection, storage, and controlled release. Microcapsules combined with tissue engineering scaffolds such as electrospun microfibers can enhance long-term local drug retention. However, the combination methods of microcapsules and fibers still need to be further explored. Here, different technical approaches to functionalize electrospun polycaprolactone (PCL) microfibers with silk fibroin (SF) microcapsules through encapsulation and surface immobilization are developed, including direct blending and emulsion electrospinning for encapsulation, as well as covalent and cleavable disulfide-linkage for surface immobilization. The results of “blending” approach show that silk microcapsules with different sizes could be uniformly encapsulated inside electrospun fibers without aggregation. To further reduce the use of organic solvents, the microcapsules in the aqueous phase can be uniformly distributed in the PCL organic phase and successfully electrospun into fibers using surfactant span-80. For surface immobilization, silk microcapsules are efficiently covalent binding to the surface of electrospun PCL fibers via click chemistry and exhibited noncytotoxic. Based on this method, with the incorporation of a disulfide bond, the linkages between microcapsule and fiber could be cleaved under reducing conditions. These microcapsule-electrospun fiber combination methods provide sufficient options for different drug delivery requirements.     

Preparation of submicron‐scale,electrospun cellulose fibers via direct dissolution

Cellulose nonwoven mats of submicron‐sized fibers (150 nm–500 nm in diameter) were obtained by electrospinning cellulose solutions. A solvent system based on lithium chloride (LiCl) and N,N‐dimethylacetamide (DMAc) was used, and the effects of (i) temperature of the collector, (ii) type of collector (aluminum mesh and cellulose filter media), and (iii) postspinning treatment, such as coagulation with water, on the morphology of electrospun fibers were investigated. The scanning electron microscopy (SEM) and X‐ray diffraction studies of as‐spun fibers at room temperature reveal that the morphology of cellulose fibers evolves with time due to moisture absorption and swelling caused by the residual salt and solvent. Although heating the collector greatly enhances the stability of the fiber morphology, the removal of salt by coagulation and DMAc by heating the collector was necessary for the fabrication of dry and stable cellulose fibers with limited moisture absorption and swelling. The presence and removal of the salt before and after coagulation have been identified by electron microprobe and X‐ray diffraction studies. When cellulose filter media is used as a collector, dry and stable fibers were obtained without the coagulation step, and the resulting electrospun fibers exhibit good adhesion to the filter media. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1673–1683, 2005     

Facile fabrication of novel polycaprolactone-based electrospun fibers using in-process water exposure

To overcome the problems related to the low surface enrichment of blended fibers from hydrophilic polymer, routine blend electrospinning setup was modified by exposing the polycaprolactone (PCL)–Pluronic P123 solution to water in order to attract the hydrophilic chains toward the fiber surface. Analysis of the modified fibers revealed a drastic surge of hydrophilic polymer surface enrichment value in comparison with that of the routine method which suggested homogenously positioned Pluronic on the surface and the subsequent reduction of its accumulations within fibers. The thermogram of the proposed method showed induced crystallization in the Pluronic section. Furthermore, the intensity of PCL characteristic peaks decreased for this method.     

Preparation,characterization, and properties of nanofibers based on poly(vinylidene fluoride) and polyhedral oligomeric silsesquioxane

Nanostructered nanofibers based on poly(vinylidene fluoride) (PVDF) and polyhedral oligomeric silsesquioxane (POSS) have been prepared by electrospinning process. The starting solutions were prepared by dissolving both the system components in the mixture N,N‐dimethylacetamide/acetone. The characteristics of the fiber prepared, studied by scanning electron microscopy, atomic force microscopy, and wide angle X‐ray diffraction, have been compared with those of PVDF fibers. Morphological characterization has demonstrated the possibility to obtain defect‐free PVDF/POSS nanofibers by properly choosing the electrospinning conditions, such as voltage, polymer concentration, humidity, etc. Conversely, in the case of fibers based on the neat polymer, it was not possible to attain the complete elimination of beads in the electrospun nanofibers. The different behavior of the two types of solutions has been ascribed to silsesquioxane molecules, which, without influencing the solution viscosity or conductivity, favor the formation of uniform structures by decreasing the system surface tension. Concerning POSS distribution in the fibers, the morphological characterization of the electrospun films has shown a submicrometric dispersion of the silsesquioxane. It is relevant to underline that cast films, prepared by the same solutions, have been found to be characterized by POSS aggregation, thus demonstrating a scarce affinity between the two‐system components. Indeed, the peculiar solvent evaporation of the electrospun solution, which is much faster than that occurring during the cast process, prevents POSS aggregation, thus leading to the formation of nanofibers characterized by a silsesquioxane dispersion similar to that present in solution. Finally, the presence of POSS improves the electrospun film mechanical properties. Copyright © 2011 John Wiley & Sons, Ltd.     

Structure and wettability relationship of coelectrospun poly (L‐lactic acid)/gelatin composite fibrous mats

Coelectrospun polylactide(PLA)/gelatin (GE) composite fibrous matrixes have been identified to exhibit much improved performances compared to the respective components; however, the reasons for their water contact angles decreasing to zero at proper PLA/GE ratios remain unclear. To get a deep understanding of the phenomenon, PLA and GE were coelectrospun with different PLA/GE ratios in this study. Although the resulting composite fibers were homogeneous in appearance, they were detected different microscopic structures by transmission electron mircroscope (TEM) and via morphological observations after selective removal of either PLA or GE component. Together with the results of degradation study in phosphate buffered solution, a kind of cocontinuous phase separation microstructure could be identified for the PLA(50 wt%)/GE(50 wt%) composite fibers, which also showed the water contact angle of 0°. This value was far lower than those of electrospun PLA (～123°) and GE (～42°) fibrous matrixes. The X‐ray photoelectron spectrometry (XPS) data revealed that the polar side groups of protein macromolecules have moved toward composite fiber surface with solvent evaporation during electrospinning, due to the hydrophobic interaction between PLA and GE. Then the excellent hydrophilicity of PLA(50 wt%)/GE(50 wt%) composite fibers could be suggested as the consequence of: (1) the cocontinuous phase separation structure could provide more interface and void for water molecules penetrating; and (2) the accumulation of polar groups on composite fiber surface significantly increased the surface wettability. Copyright © 2010 John Wiley & Sons, Ltd.     

Biomedical applications of electrospun polycaprolactone fiber mats

Polycaprolactone (PCL) is a biodegradable polyester emerging into biomedical applications because of its biodegradability, biocompatibility, chemical stability, thermal stability and good mechanical properties. Electrospinning is a versatile method using electrostatic forces for fabricating continuous ultrafine fibers that offer various advantages such as high surface area and high porosity. Thus, this method has gained interest for use in many fields, especially biomedical fields. This review focuses on researches and studies in electrospinning, PCL, electrospinning of PCL and also biomedical applications of the electrospun PCL fiber mats. Copyright © 2016 John Wiley & Sons, Ltd.     

Improved interfacial properties of carbon fiber/UHMWPE composites through surface coating on carbon fiber surface

Carbon fibers were coated in an attempt to improve the interfacial properties between carbon fibers and ultra‐high molecular weight polyethylene resin matrix. Atomic force microscopy, scanning electron microscopy, and X‐ray photoelectron spectroscopy were performed to characterize the changes of carbon fiber surface. Atomic force microscopy results show that the coating of carbon fiber significantly increased the carbon fiber surface roughness. X‐ray photoelectron spectroscopy indicates that silicon containing functional groups obviously increased after modification. Interlaminar shear strength was used to characterize the interfacial properties of the composites.     

Thermoplastic polyurethane/silica nanocomposite fibers by electrospinning

Thermoplastic polyurethane/silica nanocomposite fibers with good mechanical properties were prepared by electrospinning, using colloidal silica as the source of silica and dimethyl formamide as the solvent. The fiber morphology was examined by field emission scanning electron microscopy. The average fiber diameter is about 0.8 μm with 0–10 wt % silica, and silica nanoparticles were observed on all fiber surfaces. X‐ray photoelectron spectroscopy analysis of Si in combination with transmission electron microscopy observation suggest that silica nanoparticles have a fairly uniform distribution in the fibers rather than enriching on the fiber surfaces. Tensile tests show that the incorporation of silica nanoparticles can bring about a significant reinforcing effect without decreasing the ductility. The reinforcing effect is further confirmed by dynamic mechanical analysis. The thermoplastic polyurethane/silica composite fiber mats can adsorb gold nanoparticles after further treatment with 3‐aminopropyltriethoxysilane, demonstrating that the composite fibers could be used as functional fibers by using the properties of silica nanoparticles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Surface‐treated and multilayered poly(ε‐caprolactone) nanofiber webs exhibiting enhanced hydrophilicity

To improve the hydrophilic properties of poly(ε‐caprolactone) (PCL) nano/microfiber webs for tissue engineering scaffolds, PCL webs of various structures were fabricated by electrospinning with single or double nozzles connected to an auxiliary electrode. Surface‐modified and layered PCL fiber webs were made by including water‐soluble poly(ethylene oxide) (PEO) in the PCL electrospinning solution (single‐nozzle method) or by electrospinning of alternating PCL and PEO solutions using two nozzles (double‐nozzle method), respectively. When the PEO component within the resulting webs was removed by dissolution with distilled water, the remnant PCL webs exhibited two distinct structures. Those made by the single‐nozzle method consisted of nanofibers with high surface roughness, whereas those made by the double‐nozzle method consisted of stacked layers of PCL nanofibers. Both types of structured PCL web showed improved hydrophilicity characteristics compared with those of nanofiber webs generated from a pure PCL solution using a typical electrospinning process. Cell culturing and scanning electron microscopy showed that the interactions between human dermal fibroblasts and the structured PCL scaffolds were very favorable. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2038–2045, 2007     

Aligned and molecularly oriented semihollow ultrafine polymer fiber yarns by a facile method

In this work, aligned and molecularly oriented bone‐like PLLA semihollow fiber yarns were manufactured continuously from an optimized homogeneous polymer‐solvent‐nonsolvent system [PLLA, CH₂Cl₂, and dimethyl formamide (DMF)] by a single capillary electrospinning via self‐bundling technique. Here, it should be emphasized that the self‐bundling electrospinning technique, a very facile electrospinning technique with a grounded needle (which is to induce the self‐bundling of polymer nanofibers at the beginning of electrospinning process), is used for the alignment and molecular orientation of the polymer fiber, and the take‐up speed of the rotating drum for the electrospun fiber yarn collection is very low (0.5 m/s). PLLA can be dissolved in DMF and CH₂Cl₂ mixed solvent with different ratios. By varying the ratios of mixed solvent system, PLLA electrospun semihollow fiber with the porous inner structure and compact shell wall could be formed, the thickness of the shell and the size of inner pores could be adjusted. The results of polarized FTIR and wide angle X‐ray diffraction investigations verified that as‐prepared PLLA semihollow fiber yarns were well‐aligned and molecularly oriented. Both the formation mechanism of semihollow fibers with core‐shell structure and the orientation mechanism of polymer chains within the polymer fibers were all discussed. The as‐prepared self‐bundling electrospun PLLA fiber yarns possessed enhanced mechanical performance compared with the corresponding conventional electrospun PLLA fibrous nonwoven membranes. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1118–1125, 2010     

Preparation and characterization of novel bone scaffolds based on electrospun polycaprolactone fibers filled with nanoparticles

Novel bone-scaffolding materials were successfully fabricated by electrospinning from polycaprolactone (PCL) solutions containing nanoparticles of calcium carbonate (CaCO(3)) or hydroxyapatite (HA). The diameters of the as-spun fibers were found to increase with the addition and increasing amounts of the nanoparticles. The observed increase in the diameters of the as-spun fibers with the addition and increasing amounts of the nanoparticulate fillers was responsible for the observed increase in the tensile strength of the obtained fiber mats. An increase in the concentration of the base PCL solution caused the average diameter of the as-spun PCL/HA composite fibers to increase. Increasing applied electrical potential also resulted in an increase in the diameters of the obtained PCL/HA composite fibers. Lastly, indirect cytotoxicity evaluation of the electrospun mats of PCL, PCL/CaCO(3), and PCL/HA fibers based on human osteoblasts (SaOS2) and mouse fibroblasts (L929) revealed that these as-spun mats posed no threat to the cells, a result that implied their potential for utilization as bone-scaffolding materials.     

Photo and Thermal Cured Silicon‐Containing Diethynylbenzene Fibers via Melt Electrospinning with Enhanced Thermal Stability

An inorganic–organic hybrid material, poly(dimethylsilylene ethynylenephenyleneethynylene) (PMSEPE), was synthesized in a mild condition and its microfiber was successfully produced by melt electrospinning. The electrospinning parameters, which affected the morphology and diameter of fibers, were well investigated. To maintain the fiber structure at thermal cured temperature (above melting point), the PMSEPE fibers were enhanced via thiol‐yne photo polymerization. Followed by the thermal curing reaction, the heat‐resistance and mechanical properties of fibers were enhanced. The mechanism of two‐step curing was explored and confirmed by means of Fourier transform infrared, differential scanning calorimetry, and X‐ray photoelectron spectroscopy (XPS). Thermaogravimetric analysis and scanning electron microscopy results show that after carbonization at 800 °C, the two‐step cured fibers had only a small weight loss (20%) and the fibers can still maintain the original morphology. Moreover, the two‐step cured fiber exhibited a high tensile strength (55.4 MPa) and a small elongation at break (0.02%). All the results indicate that the fibers could be applied as fiber‐reinforced materials. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2815–2823     

Polycaprolactone Electrospun Fiber Mats Prepared Using Benign Solvents: Blending with Copper(II)‐Chitosan Increases the Secretion of Vascular Endothelial Growth Factor in a Bone Marrow Stromal Cell Line

Inducing the formation of new blood vessels (angiogenesis) is an essential requirement for successful tissue engineering. Approaches have been proposed to enhance angiogenesis using growth factors and other biomolecules; however, this approaches present drawbacks in terms of high cost and patient safety. Copper is known to effectively regulate angiogenesis and can offer a more cost‐effective alternative than the direct use of growth factors. With this study, a strategy to incorporate copper in electrospun fibrous scaffolds with pro‐angiogenic properties is presented. Polycaprolactone (PCL) and copper(II)‐chitosan are electrospun using benign solvents. The morphological and physicochemical properties of the fiber mats are investigated through scanning electron microscopy (SEM), static contact angle measurements, energy dispersive X‐ray, and Fourier‐transform infrared spectroscopies. Scaffold stability in phosphate buffered saline at 37 °C is monitored over 1 week. A bone marrow stromal cell line (ST‐2) is cultured for 7 days and its behavior is evaluated using SEM, fluorescence microscopy and a tetrazolium salt‐based colorimetric assay. Results confirm that PCL/copper(II)‐chitosan is suitable for electrospinning. The fiber mats are biocompatible and favor cell colonization and infiltration. Most notably, the angiogenic potential of PCL/copper(II)‐chitosan blends is confirmed by a three‐fold increase in VEGF secretion by ST‐2 cells in the presence of copper(II)‐chitosan.     

Hydrogen bonding interactions,crystallization, and surface hydrophobicity in nanostructured epoxy/block copolymer blends

Hydrogen bonding interactions, phase behavior, crystallization, and surface hydrophobicity in nanostructured blend of bisphenol A‐type epoxy resin (ER), for example, diglycidyl ether of bisphenol A (DGEBA) and poly(ε‐caprolactone)‐block‐poly(dimethyl siloxane)‐block‐poly(ε‐caprolactone) (PCL–PDMS–PCL) triblock copolymer were investigated by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, transmission electron microscopy, small‐angle X‐ray scattering, and contact angle measurements. The PCL–PDMS–PCL triblock copolymer consisted of two epoxy‐miscible PCL blocks and an epoxy‐immiscible PDMS block. The cured ER/PCL–PDMS–PCL blends showed composition‐dependent nanostructures from spherical and worm‐like microdomains to lamellar morphology. FTIR study revealed the existence of hydrogen bonding interactions between the PCL blocks and the cured epoxy, which was responsible for their miscibility. The overall crystallization rate of the PCL blocks in the blend decreased remarkably with increasing ER content, whereas the melting point was slightly depressed in the blends. The surface hydrophobicity of the cured ER increased upon addition of the block copolymer, whereas the surface free energy (γ_s) values decreased with increasing block copolymer concentration. The hydrophilicity of the epoxy could be reduced through blending with the PCL–PDMS–PCL block copolymer that contained a hydrophobic PDMS block. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 790–800, 2010     

Fabrication of carbon fibers with nanoporous morphologies from electrospun polyacrylonitrile/poly(L‐lactide) blends

Porous carbon nanofibers were prepared through electrospinning a blend solution of polyacrylonitrile and poly(L ‐lactide), followed by carbonization at different temperatures and in different atmospheres. Structural features of these porous carbon nanofibers were characterized using scanning electron microscopy, transmission electron microscopy, thermogravimetric analysis, X‐ray powder diffraction, and Raman spectroscopy. Surface area and pore structure were evaluated using the nitrogen adsorption technique. It was found that carbon fibers prepared by this scalable and relatively economical method exhibited a porous surface morphology with high specific surface area and large pore volume. The fiber diameter, surface area, pore volume, bulky crystalline structure, and surface crystalline structure of these carbon nanofibers showed a strong dependence on the polymer precursor composition and carbonization condition. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 493–503, 2009     

Enzymatic degradation of poly(L-lactide) and poly(epsilon-caprolactone) electrospun fibers

Poly(L-lactide) (PLLA) and poly(epsilon-caprolactone) (PCL) ultrafine fibers were prepared by electrospinning. The influence of cationic and anionic surfactants on their enzymatic degradation behavior was investigated by measuring weight loss, molecular weight, crystallinity, and melting temperature of the fibers as a function of degradation time. Under the catalysis of proteinase K, the PLLA fibers containing the anionic surfactant sodium docecyl sulfate (SDS) exhibited a faster degradation rate than those containing cationic surfactant triethylbenzylammonium chloride (TEBAC), indicating that surface electric charge on the fibers is a critical factor for an enzymatic degradation. Similarly, TEBAC-containing PCL fibers exhibited a 47% weight loss within 8.5 h whereas SDS-containing PCL fibers showed little degradation in the presence of lipase PS. By analyzing the charge status of proteinase K and lipase PS under the experimental conditions, the importance of the surface charges of the fibers and their interactions with the charges on the enzymes were revealed. Consequently, a "two-step" degradation mechanism was proposed: (1) the enzyme approaches the fiber surface; (2) the enzyme initiates hydrolysis of the polymer. By means of differential scanning calorimetry and wide-angle X-ray diffraction, the crystallinity and orientation changes in the PLLA and PCL fibers during the enzymatic degradation were investigated, respectively.     

Electrospun core–sheath fibers for integrating the biocompatibility of silk fibroin and the mechanical properties of PLCL

In the process of preparing core–sheath fibers via coaxial electrospinning, the relative evaporation rates of core and sheath solvents play a key role in the formation of the core–sheath structure of the fiber. Both silk fibroin (SF) and poly(lactide‐co‐ε‐caprolactone) (PLCL) have good biocompatibility and biodegradability. SF has better cell affinity than PLCL, whereas PLCL has higher breaking strength and elongation than SF. In this work, hexafluoroisopropanol (HFIP)‐formic acid (volume ratio 8:2), HFIP and HFIP–dichloromethane (volume ratio 8:2) were used to dissolve PLCL as the core solutions, and HFIP was used to dissolve SF as the sheath solution. Then, core–sheath structured SF/PLCL (C‐SF/PLCL) fibers were prepared by coaxial electrospinning with the core and sheath solutions. Transmission electron microscopy images indicated the existence of the core–shell structure of the fibers, and energy dispersive X‐ray analysis results revealed that the fiber mat with the greatest content of core–shell structure fibers was obtained when the core solvent was HFIP–dichloromethane (volume ratio 8:2). Tensile tests showed that the C‐SF/PLCL fiber mat displayed improved tensile properties, with strength and elongation that were significantly higher than those of the pure SF mat. The C‐SF/PLCL fiber mat was further investigated as a scaffold for culturing EA.hy926 cells, and the results showed that the fiber mat permitted cellular adhesion, proliferation and spreading in a manner similar to that of the pure SF fiber mat. These results indicated that the coaxial electrospun SF/PLCL fiber mat could be considered a promising candidate for tissue engineering scaffolds for blood vessels. Copyright © 2014 John Wiley & Sons, Ltd.     

Identification and Characterization of a Single High‐Affinity Fatty Acid Binding Site in Human Serum Albumin

A single high‐affinity fatty acid binding site in the important human transport protein serum albumin (HSA) is identified and characterized using an NBD (7‐nitrobenz‐2‐oxa‐1,3‐diazol‐4‐yl)‐C₁₂ fatty acid. This ligand exhibits a 1:1 binding stoichiometry in its HSA complex with high site‐specificity. The complex dissociation constant is determined by titration experiments as well as radioactive equilibrium dialysis. Competition experiments with the known HSA‐binding drugs warfarin and ibuprofen confirm the new binding site to be different from Sudlow‐sites I and II. These binding studies are extended to other albumin binders and fatty acid derivatives. Furthermore an X‐ray crystal structure allows locating the binding site in HSA subdomain IIA. The knowledge about this novel HSA site will be important for drug depot development and for understanding drug‐protein interaction, which are important prerequisites for modulation of drug pharmacokinetics.     

Melting and crystallization behavior of polyhedral oligomeric silsesquioxane‐capped poly(ε‐caprolactone)

In this study, we investigated the melting and crystallization behavior of polyhedral oligomeric silsesquioxane (POSS)‐capped poly(ε‐caprolactone) PCL with various lengths of PCL chains by means of X‐ray diffraction and differential scanning calorimetry. This organic–inorganic macromolecule possesses a tadpole‐like structure in which the bulky POSS cage is the “head” whereas PCL chain the “tail”. The novel organic–inorganic association result in the significant alterations in the melting and crystallization behavior of PCL. The POSS‐terminated PCL displayed the enhanced equilibrium melting points compared to the control PCL. Both the overall crystallization rate and the spherulitic growth rate of the POSS‐terminated PCLs increased with increasing the concentration of POSS (or with decreasing length of PCL chain in the hybrids). The analysis of Avrami equation shows that the crystallization of the POSS‐terminated PCL preferentially followed the mechanism of spherulitic growth with instantaneous nuclei. It is found that the folding free energy of surface for the POSS‐terminated PCLs decreased with increasing the concentration of POSS. It is found that the folding free energy of surface for the POSS‐terminated PCLs decreased with increasing the concentration of POSS. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 2201–2214, 2007