Chemistry on electrospun polymeric nanofibers: merely routine chemistry or a real challenge?

Nanofiber-based non-wovens can be prepared by electrospinning. The chemical modification of such nanofibers or chemistry using nanofibers opens a multitude of application areas and challenges. A wealth of chemistry has been elaborated in recent years on and with electrospun nanofibers. Known methods as well as new methods have been applied to modify the electrospun nanofibers and thereby generate new materials and new functionalities. This Review summarizes and sorts the chemistry that has been reported in conjunction with electrospun nanofibers. The major focus is on catalysis and nanofibers, enzymes and nanofibers, surface modification for biomedical and specialty applications, coatings of fibers, crosslinking, and bulk modifications. A critical focus is on the question: what could make chemistry on or with nanofibers different from bulk chemistry?

Collagen matrices from sponge to nano: new perspectives for tissue engineering of skeletal muscle.

BACKGROUND: Tissue engineering of vascularised skeletal muscle is a promising method for the treatment of soft tissue defects in reconstructive surgery. In this study we explored the characteristics of novel collagen and fibrin matrices for skeletal muscle tissue engineering. We analyzed the characteristics of newly developed hybrid collagen-I-fibrin-gels and collagen nanofibers as well as collagen sponges and OPLA-scaffolds. Collagen-fibrin gels were also tested with genipin as stabilizing substitute for aprotinin. RESULTS: Whereas rapid lysis and contraction of pure collagen I- or fibrin-matrices have been great problems in the past, the latter could be overcome by combining both materials. Significant proliferation of cultivated myoblasts was detected in collagen-I-fibrin matrices and collagen nanofibers. Seeding cells on parallel orientated nanofibers resulted in strongly aligned myoblasts. In contrast, common collagen sponges and OPLA-scaffolds showed less cell proliferation and in collagen sponges an increased apoptosis rate was evident. The application of genipin caused deleterious effects on primary myoblasts. CONCLUSION: Collagen I-fibrin mixtures as well as collagen nanofibers yield good proliferation rates and myogenic differentiation of primary rat myoblasts in vitro In addition, parallel orientated nanofibers enable the generation of aligned cell layers and therefore represent the most promising step towards successful engineering of skeletal muscle tissue.

Influence of poly-(L-lactic acid) nanofiber functionalization on maximum load, Young's modulus, and strain of nanofiber scaffolds before and after cultivation of osteoblasts: an in vitro study.

The aim of this study was to characterize the influence of functionalization of synthetic poly-(L-lactic acid) (PLLA) nanofibers on mechanical properties such as maximum load, elongation, and Young's modulus. Furthermore, the impact of osteoblast growth on the various nanofiber scaffolds stability was determined. Nanofiber matrices composed of PLLA, PLLA-collagen, or BMP-2-incorporated PLLA were produced from different solvents by electrospinning. Standardized test samples of each nanofiber scaffold were subjected to failure protocol before or after incubation in the presence of osteoblasts over a period of 22 days under osteoinductive conditions. PLLA nanofibers electrospun from hexafluoroisopropanol (HFIP) showed a higher strain and tended to have increased maximum loads and Young s modulus compared to PLLA fibers spun from dichloromethane. In addition, they had a higher resistance during incubation in the presence of cells. Functionalization by incorporation of growth factors increased Young's modulus, independent of the solvent used. However, the incorporation of growth factors using the HFIP system resulted in a loss of strain. Similar results were observed when PLLA was blended with different ratios of collagen. Summarizing the results, this study indicates that different functionalization strategies influence the mechanical stability of PLLA nanofibers. Therefore, an optimization of nanofibers should not only account for the optimization of biological effects on cells, but also has to consider the stability of the scaffold.

Characterization of a PLLA-collagen I blend nanofiber scaffold with respect to growth and osteogenic differentiation of human mesenchymal stem cells.

We developed a nanofiber scaffold by blending PLLA with collagen I, suitable for bone regeneration. Among several PLLA-COLI ratios tested, cell growth was better enhanced when blends with a ratio of PLLA-COLI 4:1 were used. Here, growth as well as osteoblast differentiation of hMSC was improved when compared to PLLA nanofibers alone. Therefore, blending is a suitable tool to enhance PLLA nanofibers with respect to bone tissue engineering.

Influence of poly(L-lactic acid) nanofibers and BMP-2-containing poly(L-lactic acid) nanofibers on growth and osteogenic differentiation of human mesenchymal stem cells.

The aim of this study was to characterize synthetic poly-(L-lactic acid) (PLLA) nanofibers concerning their ability to promote growth and osteogenic differentiation of stem cells in vitro, as well as to test their suitability as a carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2-incorporated PLLA were seeded with human mesenchymal stem cells and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and collagen I (COL-I). Furthermore, COL-I and OC deposition, as well as cell densities and proliferation, were analyzed using fluorescence microscopy. Although the presence of nanofibers diminished the dexamethasone-induced proliferation, there were no differences in cell densities or deposition of either COL-I or OC after 22 days of culture. The gene expression of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA nanofibers as compared to cover slip control, but normalized during the course of cultivation. The initial down-regulation was not observed when BMP-2 was directly incorporated into PLLA nanofibers by electrospinning, indicating that growth factors like BMP-2 might survive the spinning process in a bioactive form.

Electrospinning: a fascinating method for the preparation of ultrathin fibers.

Electrospinning is a highly versatile method to process solutions or melts, mainly of polymers, into continuous fibers with diameters ranging from a few micrometers to a few nanometers. This technique is applicable to virtually every soluble or fusible polymer. The polymers can be chemically modified and can also be tailored with additives ranging from simple carbon-black particles to complex species such as enzymes, viruses, and bacteria. Electrospinning appears to be straightforward, but is a rather intricate process that depends on a multitude of molecular, process, and technical parameters. The method provides access to entirely new materials, which may have complex chemical structures. Electrospinning is not only a focus of intense academic investigation; the technique is already being applied in many technological areas.

Nondestructive mechanical release of ordered polymer microfiber arrays from porous templates.

The fabrication of one-dimensional (1D) nanostructures and microstructures inside the pores of porous templates is intensively investigated. The release of these structures is commonly accomplished by etching and destroying the templates. The 1D nanostructures and microstructures tend to condense because of the occurrence of capillary forces during drying of the specimens. It is shown that highly ordered arrays of polymer microfibers can be easily detached from silanized porous templates by mechanical lift-off. This procedure leaves the templates intact, thus allowing their recycling, and does not involve the use of solutions or solvents, thus circumventing condensation. Therefore, mechanical lift-off may enable the up-scaling of template-based approaches to the fabrication of highly ordered assemblies of 1D nanostructures and microstructures.

Advantages and challenges offered by biofunctional core-shell fiber systems for tissue engineering and drug delivery.

Whereas highly porous scaffolds composed of electrospun nanofibers can mimick major features of the extracellular matrix in tissue engineering, they lack the ability to incorporate and release biocompounds (drugs, growth factors) safely in a controlled way. Here, electrospun core-shell fibers (core made from water and aqueous solutions of hydrophilic polymers and the shell from materials with well-defined release mechanisms) offer unique advantages in comparison with those that have helped make porous nanofibrillar scaffolds highly successful in tissue engineering. This review considers the preparation and biofunctionalization of such core-shell fibers as well as applications in various areas, including neural, vascular, cardiac, cartilage and bone tissue engineering, and touches on the topic of clinical trials.

Nanotubes by template wetting: a modular assembly system.

The wetting of porous templates with polymer melts and solutions or polymer-containing mixtures is a simple and versatile method for the preparation of tubular structures with diameters ranging from a few tens of nanometers to micrometers. The tube walls can be made of a multitude of materials, some of which have thus far been altogether impossible to use or very limited in their ability to be incorporated into nanostuctures. Template wetting also makes it possible to modify the nanotubes in a variety of ways, for example through the controlled generation of pores or the embedding of nanoparticles into the walls. This method offers a promising approach to functionalized nanotube-template hybrid systems and free-standing nanotubes.

Polymer-assisted preparation of nanoscale films of thermoelectric PbSe and PbTe and of lead chalcogenide-polymer composite films.

Polymer films of polyethyleneoxide (PEO) or poly(L-lactide) (PLLA) containing a single-source precursor for either PbSe or PbTe were used to produce films of nanoparticles of these thermoelectric materials. The monomeric homoleptic chalcogenolates lead(II) bis-(2,4,6-trifluoromethylphenylselenolate) Pb[SeC(6)H(2)(CF(3))(3)](2) and lead(II) bis-[tris(trimethylsilyl)silyl-tellurolate] Pb[TeSi(SiMe(3))(3)](2) were used as single-source precursors for the thermolytic formation of the lead chalcogenides. The thickness and the quality of as-obtained thin films depended decisively on the spin-coating conditions, on the polymer, on the precursor concentration in the composite film before thermolysis and on the annealing time. Thin layers of particles of 30-50 nm size and high crystallinity were obtained. They were characterized by X-ray diffraction, thermal analysis and electron microscopy.

Progress in the field of electrospinning for tissue engineering applications.

Electrospinning is an extremely promising method for the preparation of tissue engineering (TE) scaffolds. This technique provides nonwovens resembling in their fibrillar structures those of the extracellular matrix (ECM), and offering large surface areas, ease of functionalization for various purposes, and controllable mechanical properties. The recent developments toward large-scale productions combined with the simplicity of the process render this technique very attractive. Progress concerning the use of electrospinning for TE applications has advanced impressively. Different groups have tackled the problem of electrospinning for TE applications from different angles. Nowadays, electrospinning of the majority of biodegradable and biocompatible polymers, either synthetic or natural, for TE applications is straightforward. Different issues, such as cell penetration, incorporation of growth and differentiating factors, toxicity of solvents used, productivity, functional gradient, etc. are main points of current considerations. The progress in the use of electrospinning for TE applications is highlighted in this article with focus on major problems encountered and on various solutions available until now.

Polymer fibers as carriers for homogeneous catalysts.

This paper describes a polymer fiber-based approach for the immobilization of homogeneous catalysts. The goal is to generate products that are free of catalysts which would be of great importance for the development of optoelectronic or pharmaceutical compounds. Electrospinning was employed to prepare the non-woven fiber assembly composed of polystyrene. The homogeneous catalyst scandium triflate was immobilized on the polystyrene fibers during electrospinning and on corresponding core shell fibers using a fiber template approach. An imino aldol and an aza-Diels-Alder model reaction were carried out with each fibrous catalytic system. This resulted in the immobilization of homogeneous catalysts in a polymer environment without loss of their catalytic activity and may even be enhanced when compared with reactions carried out in homogeneous solutions.

Electrospinning approaches toward scaffold engineering--a brief overview.

Tissue engineering involves the in vitro seeding of cells onto scaffolds which assume the role of supporting cell adhesion, migration, proliferation, and differentiation, and which define the three-dimensional shape of the tissue to be engineered. Among the various types of scaffold architectures available, scaffolds based on nanofibers mimicking to a certain extent the structure of the extracellular matrix offer great advantages. Electrospinning is the technique of choice for the preparation of such scaffolds. Investigations have revealed that the nanofibrous structure promotes cell adhesion, proliferation, and differentiation. Parameters relevant for these processes such as fiber diameters, surface topology, porosity, mechanical properties, and the fibrous architecture of the scaffold can be controlled by electrospinning in a broad range.

Coating of poly(p-xylylene) by PLA-PEO-PLA triblock copolymers with excellent polymer-polymer adhesion for stent applications.

Poly(p-xylylene) (PPX) was deposited by chemical vapor deposition (CVD) on stainless steel substrates. These PPX films were coated by solution casting of poly(lactide)-poly(ethylene oxide)-poly(lactide) triblock copolymers (PLA-PEO-PLA) loaded with 14C-labeled paclitaxel. Adhesion of PLA-PEO-PLA on PPX substrate coatings was measured using the blister test method. Excellent adhesion of the block copolymers on PPX substrates was found. Stress behavior and film integrity of PLA-PEO-PLA was compared to pure PLA on unexpanded and expanded stent bodies and was found to be superior for the block copolymers. The release of paclitaxel from the biodegradable coatings was studied under physiological conditions using the scintillation counter method. Burst release of paclitaxel was observed from PLA-PEO-PLA layers regardless of composition, but an increase in paclitaxel loading was observed with increasing content of PEO.

Biocompatible and biodegradable polymer nanofibers displaying superparamagnetic properties.

Superparamagnetic polymer nanofibers intended for drug delivery and therapy are considered here. Magnetite (Fe3O4) nanoparticles in the diameter range of 5-10 nm were synthesized in aqueous solution. Polymer nanofibers containing magnetite nanoparticles were prepared from commercially available poly(hydroxyethyl methacrylate), PHEMA, and poly-L-lactide (PLLA) by the electrospinning technique. Nanofibers with diameters ranging from 50 to 300 nm were obtained. Nanofibers containing up to 35 wt % magnetite nanoparticles displayed superparamagnetism at room temperature. The blocking temperature was about 50 K for an applied field of 500 Oe, and the saturation magnetization was 3.5 emu g(-1) and 1.1 emu g(-1) for Fe3O4/PHEMA and Fe3O4/PLLA nanofibers, respectively, and depended on the amount of Fe3O4 nanoparticles in the nanocomposites. To test such magnetic nano-objects for applications as drug carriers and drug-release systems we incorporated a fluorescent albumin with dog fluorescein isothiocyanate (ADFI).

Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings.

Protein-loaded (bovine serum albumin (BSA) or luciferase) poly(vinyl alcohol) (PVA) nanofibers were obtained by electrospinning. Poly(p-xylylene) (PPX, also coined as parylene) coated PVA/BSA nanofibers were prepared by chemical vapor deposition (CVD). The release of BSA from PVA nanofibers under physiological conditions was monitored by absorption spectroscopy. Burst release of BSA was noted with uncoated PVA nanofibers. In contrast, PPX-coated nanofibers exhibited a significantly retarded release of BSA depending on the coating thickness of PPX (ranging from 40 to 300 nm). Luciferase was used here as model enzyme, which after electrospinning retained its enzyme activity. This preservation of enzyme activity and the continuous release of the intact enzyme from the immersed fibers meets a fundamental prerequisite for the application of enzymes or other sensitive agents released from electrospun nanofibers under physiological conditions.

Liquid crystalline nanowires in porous alumina: geometric confinement versus influence of pore walls.

Aligned liquid crystalline nanowires within ordered porous alumina templates show a pronounced texture on a macroscopic scale. We have investigated the influence of the geometric confinement and the nature of the pore walls on the mesophase formation by means of X-ray diffraction. The apparent texture is the result of a complex interplay of the pore geometry, interfacial phenomena, and the thermal history. Pores with a diameter of a few hundred nm guide the mesophase formation more efficiently than those with a diameter below 100 nm.

Nanotubes à la carte: wetting of porous templates.

Nanotubes have an outstanding potential both for applications in nanotechnology and as the subject of basic research. Wetting of porous templates is a simple technique that overcomes many limitations of established preparation methods. It extends the range of processable materials, for example, by a broad range of multicomponent mixtures or by high-performance polymers such as poly(oxy-1,4-phenyleneoxy-1,4-phenylenecarbonyl-1,4-phenylene) (PEEK) and polytetrafluoroethylene (PTFE). Inducing controlled phase transitions generates a large specific surface, a specific nanoporosity, or oriented crystalline domains within the nanotube walls. Template wetting provides customized nanotubes and allows us to investigate how the wall curvature affects the structure formation.

Design, synthesis, and properties of new biodegradable aromatic/aliphatic liquid crystalline copolyesters.

Liquid crystalline copolyesters of high molecular weight were obtained by polycondensation of aromatic diols, diacyl dichlorides, oligolactides, and poly(ethylene glycol)s. Hydrophilicity of the copolyesters was controlled by the content of ethyleneoxy moieties as verified by contact angle measurements. Copolyesters with ethyleneoxy moieties showed significant enhancement of degradability under physiological conditions in comparison to copolyester without ethyleneoxy moieties, which makes these copolyesters promising materials for bone tissue engineering as also verified by hardness testing and mechanical testing.

Hydrolytic and enzymatic degradation of liquid-crystalline aromatic/aliphatic copolyesters.

Aromatic/aliphatic copolyesters containing hydrophilic moieties in the main chain or side chain were synthesized by bulk polycondensation of aromatic monomers without or with solubilizing substituents and aliphatic monomers. Hydrolytic and enzymatic degradation studies were carried out in vitro at 37 degrees C in pH 7.4 phosphate buffer and in Tris-HCl buffer containing proteinase K. The results indicate that liquid-crystalline aromatic/aliphatic copolyesters are degradable hydrolytically as well as enzymatically. The change in composition and morphology of the polyester films were monitored by nuclear magnetic resonance and scanning electron microscopy. The results suggested that aromatic species and aliphatic moieties could be released into aqueous solution during hydrolytic degradation of aromatic/aliphatic copolyesters with ethyleneoxy groups on the side chain. Modifying aromatic species with hydrophilic groups in aromatic/aliphatic copolyesters was an efficient method to improve degradability and biocompatibility due to improved solubility of degradation products in aqueous solution. Mechanical tests indicated that the copolyesters exhibited good mechanical properties prior to degradation, which can be of relevance for bone tissue engineering.