Yanzhong Zhang

A review on polymer nanofibers by electrospinning and their applications in nanocomposites

Electrospinning has been recognized as an efficient technique for the fabrication of polymer nanofibers. Various polymers have been successfully electrospun into ultrafine fibers in recent years mostly in solvent solution and some in melt form. Potential applications based on such fibers specifically their use as reinforcement in nanocomposite development have been realized. In this paper, a comprehensive review is presented on the researches and developments related to electrospun polymer nanofibers including processing, structure and property characterization, applications, and modeling and simulations. Information of those polymers together with their processing conditions for electrospinning of ultrafine fibers has been summarized in the paper. Other issues regarding the technology limitations, research challenges, and future trends are also discussed.

Electrospun Biomimetic Fibrous Scaffold from Shape Memory Polymer of PDLLA-co-TMC for Bone Tissue Engineering

Multifunctional fibrous scaffolds, which combine the capabilities of biomimicry to the native tissue architecture and shape memory effect (SME), are highly promising for the realization of functional tissue-engineered products with minimally invasive surgical implantation possibility. In this study, fibrous scaffolds of biodegradable poly(d,l-lactide-co-trimethylene carbonate) (denoted as PDLLA-co-TMC, or PLMC) with shape memory properties were fabricated by electrospinning. Morphology, thermal and mechanical properties as well as SME of the resultant fibrous structure were characterized using different techniques. And rat calvarial osteoblasts were cultured on the fibrous PLMC scaffolds to assess their suitability for bone tissue engineering. It is found that by varying the monomer ratio of DLLA:TMC from 5:5 to 9:1, fineness of the resultant PLMC fibers was attenuated from ca. 1500 down to 680 nm. This also allowed for readily modulating the glass transition temperature Tg (i.e., the switching temperature for actuating shape recovery) of the fibrous PLMC to fall between 19.2 and 44.2 °C, a temperature range relevant for biomedical applications in the human body. The PLMC fibers exhibited excellent shape memory properties with shape recovery ratios of Rr > 94% and shape fixity ratios of Rf > 98%, and macroscopically demonstrated a fast shape recovery (∼10 s at 39 °C) in the pre-deformed configurations. Biological assay results corroborated that the fibrous PLMC scaffolds were cytocompatible by supporting osteoblast adhesion and proliferation, and functionally promoted biomineralization-relevant alkaline phosphatase expression and mineral deposition. We envision the wide applicability of using the SME-capable biomimetic scaffolds for achieving enhanced efficacy in repairing various bone defects (e.g., as implants for healing bone screw holes or as barrier membranes for guided bone regeneration).

Polyelectrolyte multilayer functionalized mesoporous silica nanoparticles for pH-responsive drug delivery: layer thickness-dependent release profiles and biocompatibility

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient approach to enhance the biocompatibility and efficiency of MSN-based carrier systems. Herein, polyelectrolyte multilayers (PEMs) composed of poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) were coated onto the MSN surface via a layer-by-layer (LbL) technique, and doxorubicin hydrochloride (DOX) was loaded into the prepared PEM-MSNs, thus constructing potential pH-responsive carrier systems. Extensive studies were performed to evaluate their biocompatibility and efficiency, emphasizing the influences of the layer numbers on the release profiles, cytotoxicity and hemocompatibility. It is demonstrated that PEM layer thickness has an exponential relationship with the number of coated layers, and release profiles of nanoparticles were both pH- and layer thickness-dependent. PEM-MSNs exhibited a very low and layer thickness-dependent cytotoxicity against macrophage cells. They did not induce obvious hemolysis or cause significant platelet aggregation, but also did not activate any coagulation pathways. The cellular uptake of DOX-loaded PEM-MSNs in HeLa cells was remarkably larger than that in L929 cells, thus resulting in a desirable growth-inhibiting effect on cancer cells. DOX-loaded PEM-MSNs exhibited a slower and prolonged DOX accumulation in the nucleus than free DOX. In vivo biodistribution indicated that they induced a sustained drug concentration in blood plasma but lower drug accumulation in the major organs, especially in the heart, compared to free DOX. The histological results also revealed that DOX-loaded PEM-MSNs had lower systemic toxicity than free DOX. Therefore, LbL functionalization of MSNs provides the practical possibility for creating MSN-based carrier systems with low systemic toxicity and high efficiency.

Au/polypyrrole@Fe3O4 nanocomposites for MR/CT dual-modal imaging guided-photothermal therapy: an in vitro study.

Construction of multifunctional nanocomposites as theranostic platforms has received considerable biomedical attention. In this study, a triple-functional theranostic agent based on the cointegration of gold nanorods (Au NRs) and superparamagnetic iron oxide (Fe3O4) into polypyrrole was developed. Such a theranostic agent (referred to as Au/PPY@Fe3O4) not only exhibits strong magnetic property and high near-infrared (NIR) optical absorbance but also produces high contrast for magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Importantly, under the irradiation of the NIR 808 nm laser at the power density of 2 W/cm(2) for 10 min, the temperature of the solution containing Au/PPY@Fe3O4 (1.4 mg/mL) increased by about 35 °C. Cell viability assay showed that these nanocomposites had low cytotoxicity. Furthermore, an in vitro photothermal treatment test demonstrates that the cancer cells can be efficiently killed by the photothermal effects of the Au/PPY@Fe3O4 nanocomposites. In summary, this study demonstrates that the highly versatile multifunctional Au/PPY@Fe3O4 nanocomposites have great potential in simultaneous multimodal imaging-guided cancer theranostic applications.

Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy.

Photothermal cancer therapy has attracted considerable interest for cancer treatment in recent years, but the effective photothermal agents remain to be explored before this strategy can be applied clinically. In this study, we therefore develop flower-like molybdenum disulfide (MoS2) nanoflakes and investigate their potential for photothermal ablation of cancer cells. MoS2 nanoflakes are synthesized via a facile hydrothermal method and then modified with lipoic acid-terminated polyethylene glycol (LA-PEG), endowing the obtained nanoflakes with high colloidal stability and very low cytotoxicity. Upon irradiation with near infrared (NIR) laser at 808 nm, the nanoflakes showed powerful ability of inducing higher temperature, good photothermal stability and high photothermal conversion efficiency. The in vitro photothermal effects of MoS2-PEG nanoflakes with different concentrations were also evaluated under various power densities of NIR 808-nm laser irradiation, and the results indicated that an effective photothermal killing of cancer cells could be achieved by a low concentration of nanoflakes under a low power NIR 808-nm laser irradiation. Furthermore, cancer cell in vivo could be efficiently destroyed via the photothermal effect of MoS2-PEG nanoflakes under the irradiation. These results thus suggest that the MoS2-PEG nanoflakes would be as promising photothermal agents for future photothermal cancer therapy.

Acetic-Acid-Mediated Miscibility toward Electrospinning Homogeneous Composite Nanofibers of GT/PCL

In tissue engineering research, there has recently been considerable interest in using electrospun biomimetic nanofibers of hybrids, in particular, from natural and synthetic polymers for engineering different tissues. However, phase separation between a pair of much dissimilar polymers might give rise to detrimental influences on both the electrospinning process and the resultant fiber performance. A representative natural-synthetic hybrid of gelatin (GT) and polycaprolactone (PCL) (50:50) was employed to study the phase separation behavior in electrospinning of the GT/PCL composite fibers. Using trifluoroethanol (TFE) as the cosolvent of the two polymers, observation of visible sedimentation and flocculation from dynamic light scattering analysis of the GT/PCL/TFE mixture both showed that phase separation does occur in just a few hours. This consequently led to gradually deteriorated fiber morphologies (e.g., splash, fiber bonding, and varied fiber size) over time during electrospinning GT/PCL. Quantitative analysis also indicated that the ratio of GT to PCL in the resultant GT/PCL fibers was altered over time. To address the phase separation related issues, a tiny amount (<0.3%) of acetic acid was introduced to improve the miscibility, which enabled the originally turbid solution to become clear immediately and to be single-phase stable for more than 1 week. Nanofibers thus obtained also appeared to be thinner, smooth, and homogeneous with enhanced performance in wettability and mechanical properties. Given the versatility and widely uses of the electrospun GT/PCL and other similar natural-synthetic hybrid systems in constructing tissue-engineered scaffolds, this work may offer a facile and effective approach to achieve finer and compositionally homogeneous hybrid nanofibers for effective applications.

Engineering aligned electrospun PLLA microfibers with nano-porous surface nanotopography for modulating the responses of vascular smooth muscle cells

In tissue engineering research, aligned electrospun ultrafine fibers have been shown to regulate cellular alignment and relevant functional expression, but the imposed effect of individual fiber surface nanotopography on cell behaviour has not been examined closely. This work investigates the impact of superimposing a nano-pore feature atop individual fiber surfaces on the responsive behaviour of human vascular smooth muscle cells (vSMCs) for blood vessel tissue engineering. Well-aligned ultrafine poly(l-lactic acid) (PLLA) microfibers with an average fiber diameter of ca. 1.6 μm were fabricated by using a novel stable jet electrospinning (SJES) method. Ellipse-shaped nano-pores with varied aspect ratios (defined as long-to-short axis ratio) of 2.7-3.9, corresponding to a surface nano-roughness in the range of 54.8-110.0 nm, were in situ generated onto individual fiber surfaces by varying ambient humidity from 45% to 75% during the SJES process. The presence of elliptical nano-pores on fiber surfaces affected the characteristic anisotropic wettability of the aligned PLLA fibers and contributed to greater protein adsorption (up to 17.59 μg mg-1). A 7 day in vitro assessment of human umbilical arterial SMCs cultured on these aligned nano-porous fiber substrates indicated that cellular responses were in close correlation with the elliptical nano-pore feature. A pronounced fiber surface nanotopography was superior in soliciting favorable cellular responses, leading to enhanced cell attachment, proliferation, alignment, expression of the vascular matrix proteins and maintenance of a contractile phenotype. This study thus suggests that introduction of an elliptical nano-pore feature to the aligned microfiber surfaces could provide additional dimensionality of topographical cues to modulate the vSMC responses when using the aligned electrospun ultrafine fibers for engineering vascular constructs.

Ultrasound-Modulated Shape Memory and Payload Release Effects in a Biodegradable Cylindrical Rod Made of Chitosan-Functionalized PLGA Microspheres

Minimally invasive implants and/or scaffolds integrated with multiple functionalities are of interest in the clinical settings. In this paper, chitosan (CTS) functionalized poly(lactic-co-glycolic acid) (PLGA) microspheres containing a model payload, lysozyme (Lyz), were prepared by a water-in-oil-in-water emulsion method, from which cylindrical shaped rod (5 mm in diameter) was fabricated by sintering the composite microspheres in a mold. High-intensity focused ultrasound (HIFU) was then employed as a unique technique to enable shape memory and payload release effects of the three-dimensional (3-D) structure. It was found that incorporation of CTS into PLGA microspheres could regulate the transition temperature Ttrans of the microsphere from 45 to 50 °C and affect shape memory ratio of the fabricated cylindrical rod to some extent. Shape memory test and drug release assay proved that HIFU could modulate the shape recovery process and synchronize the release kinetics of the encapsulated Lyz in the rod in a switchable manner. Moreover, the two processes could be manipulated by varying the acoustic power and insonation duration. Mechanical tests of the microspheres-based rod before and after ultrasound irradiation revealed its compressive properties in the range of trabecular bone. Examination of the degradation behavior indicated that the introduction of CTS into the PLGA microspheres also alleviated acidic degradation characteristic of the PLGA-dominant cylindrical rod. With HIFU, this study thus demonstrated the desired capabilities of shape recovery and payload release effects integrated in one microspheres-based biodegradable cylindrical structure.

Rapid mineralization of porous gelatin scaffolds by electrodeposition for bone tissue engineering

In bone tissue engineering, rapid mineralization of polymeric scaffolds is of particular importance in protecting the encapsulated therapeutic drugs or growth factors from loss and degradation. Here, we present a simple and rapid approach to the fabrication of mineralized porous scaffolds for bone tissue engineering. In this approach, three-dimensional (3-D) porous gelatin scaffolds were firstly fabricated by freeze-drying followed by an electrodeposition process for mineralization. We show that a high-quality apatite coating on the gelatin scaffold could be achieved within a couple of hours by electrodeposition. Increasing the deposition voltage or electrolyte temperature favored to the formation of large amounts of apatite coatings with compositions dominated by the hydroxyapatite crystals, whereas the presence of ultrasonic field facilitated the production of homogeneous apatite coatings. Moreover, biological assays indicated that the mineralized scaffolds exhibited better support for the proliferation and osteoblastic differentiation of MC3T3-E1 cells over a neat gelatin scaffold, especially for the case of mineralized scaffolds by electrodeposition at 60 °C. Therefore, the method developed would be highly desired for the rapid mineralization of polymer scaffolds in which biological molecules were loaded for functional bone tissue engineering applications.

Genipin-crosslinked electrospun chitosan nanofibers: Determination of crosslinking conditions and evaluation of cytocompatibility

To improve durability in wet conditions, electrospun chitosan (CTS) nanofibers were submersed into PBS (pH 7.4) solutions containing varied amounts of genipin (GP 0.1, 0.5, and 1% w/v) for crosslinking treatment. GP-crosslinking allowed the electrospun CTS nanofibers to maintain their fibrous morphology in wet state. Maximum tensile strength, 84.2% of the dry state strength, was attained when crosslinking was performed in GP 0.5% solution. GP-crosslinking also endowed the CTS nanofibers with enhanced resistances to swelling and enzymatic degradation. GP-crosslinked CTS nanofibers were found to significantly promote the adhesion and growth of the L929 fibroblasts, with the most suitable sample was the one crosslinked in the GP 0.5% solution as well. Our results suggest that crosslinking with the 0.5% GP in PBS could yield CTS nanofibers with improved wet stability in nanofiber structure and optimized mechanical and biological performances.