Graphene oxide (GO) has received increasing attention in bioengineering fields due to its unique biophysical and electrical properties, along with excellent biocompatibility. The application of GO nanoparticles (GO‐NPs) to engineer self‐renewal and differentiation of human fetal neural stem cells (hfNSCs) is reported. GO‐NPs added to hfNSC culture during neurosphere formation substantially promote cell‐to‐cell and cell‐to‐matrix interactions in neurospheres. Accordingly, GO‐NP‐treated hfNSCs show enhanced self‐renewal ability and accelerated differentiation compared to untreated cells, indicating the utility of GO in developing stem cell therapies for neurogenesis.
Aggregation‐caused quenching (ACQ) is a general phenomenon that is faced by traditional fluorescent polymers. Aggregation‐induced emission (AIE) is exactly opposite to ACQ. AIE molecules are almost nonemissive in their molecularly dissolved state, but they can be induced to show high fluorescence in the aggregated or solid state. Incorporation of AIE phenomenon into polymer design has yielded various polymers with AIE characteristics. In this review, the recent progress of AIE polymers for biological applications is summarized.
Cell sorting is important for cell biology and regenerative medicine. A visible light‐responsive cell scaffold is produced using gold nanoparticles and collagen gel. Various kinds of cells are cultured on the visible light‐responsive cell scaffold, and the target cells are selectively detached by photoirradiation without any cytotoxicity. This is a new image‐guided cell sorting system.
Manipulated roughness has been etched on nanofibers to modulate adsorption of serum proteins for serum‐free cells cultivation. Mixtures of Polycaprolactone and Pluronic with various blending ratios are electrospun to nanofibers and Pluronic is subsequently leached out by methanol. Electron microscopy reveals that surface roughness of the nanofibers is changed according to the contents of Pluronic. Both weight loss monitoring and NMR spectroscopy confirm that all Pluronic is leached out after methanol treatment. Water swelling ratio and protein adsorption of rougher nanofibers are higher than those of smoother ones. Also, when serum incorporation on the nanofibers is estimated in 0.01–10% serum solution, rougher nanofibers show higher serum incorporation and those soaked in 10% serum solution are employed for serum‐free cell cultivation. Viability of the cells cultivated on rougher nanofibers is much higher after 24 h. Thus, Pluronic‐induced leaching‐out strategy can be potentially employed for fabricating roughness on nanofibers for enhancing protein adsorption for serum‐free cell cultivation.
Well‐defined poly(ethylene glycol)‐b‐allyl functional polylactide‐b‐polylactides (PEG‐APLA‐PLAs) are synthesized through sequential ring‐opening polymerization. PEG‐APLA‐PLAs that have amphiphilic properties and reactive allyl side chains on their intermediate blocks are successfully transferred to core–shell interface cross‐linked micelles (ICMs) by micellization and UV‐initiated irradiation. ICMs have demonstrated enhanced colloidal stability in physiological‐mimicking media. Hydrophobic molecules such as Nile Red or doxorubicin (Dox) are readily loaded into ICMs; the resulting drug‐ICM formulations possess slow and sustained drug release profiles under physiological‐mimicking conditions. ICMs exhibit negligible cytotoxicity in human uterine sarcoma cancer cells by using biodegradable aliphatic polyester as the hydrophobic segments. Relative to free Dox, Dox‐loaded ICMs show a reduced cytotoxicity due to the late intracellular release of Dox from ICMs. Overall, ICMs represent a new type of biodegradable cross‐linked micelle and can be employed as a promising platform for delivering a broad variety of hydrophobic drugs.
The authors report a method to prepare cell‐laden, cell‐sized microparticles from various materials suitable for individual applications. The method includes a piezoelectric inkjetting technology and a horseradish peroxidase (HRP)‐catalyzed crosslinking reaction. The piezoelectric inkjetting technology enables production of cell‐laden, cell‐sized (20–60 μm) droplets from a polymer aqueous solution. The HRP‐catalyzed crosslinking of the polymer in the ejected solution enables production of spherical microparticles from various materials. Superior cytocompatibility of the microencapsulation method is confirmed from the viability and growth profiles of normal murine mammary gland epithelial cells.
In this study, heparin‐mimicking hydrogel thin films are covalently attached onto poly(ether sulfone) membrane surfaces to improve anticoagulant property. The hydrogel films display honeycomb‐like porous structure with well controlled thickness and show long‐term stability. After immobilizing the hydrogel films, the membranes show excellent anticoagulant property confirmed by the activated partial thromboplastin time values exceeding 600 s. Meanwhile, the thrombin time values increase from 20 to 61 s as the sodium allysulfonate proportions increase from 0 to 80 mol%. In vitro investigations of protein adsorption and blood‐related complement activation also confirm that the membranes exhibit super‐anticoagulant property. Furthermore, gentamycin sulfate is loaded into the hydrogel films, and the released drug shows significant inhibition toward E. coli bacteria. It is believed that the surface attached heparin‐mimicking hydrogel thin films may show high potential for the applications in various biological fields, such as blood contacting materials and drug loading materials.
Although chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western world, it remains incurable with conventional chemotherapeutic agents. Tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) is an antitumor candidate in cancer therapy. This study examines the proapoptotic effects of poly(propylene imine) (PPI) glycodendrimers modified with the maltotriose residues (PPI‐G4‐OS‐Mal‐III and PPI‐G4‐DS‐Mal‐III) on the TNF family in CLL cells. The combination of an understanding of the signaling pathways associated with CLL and the development of a molecular profiling is a key issue for the design of personalized approaches to therapy. Gene expression is determined with two‐color microarray 8 × 60K. The findings indicate that PPI‐G4‐OS/DS‐Mal‐III affect gene expression from the TRAIL apoptotic pathway and exert a strong effect on CLL cells comparable with fludarabine. Dendrimer‐targeted technology may well prove to bridge the gap between the ineffective treatment of today and the effective personalized therapy of the future.
Multivalent aptamer–siRNA conjugates containing multiple mucin‐1 aptamers and BCL2‐specific siRNA are synthesized, and doxorubicin, an anthracycline anticancer drug, is loaded into these conjugates through intercalation with nucleic acids. These doxorubicin‐incorporated multivalent aptamer–siRNA conjugates are transfected to mucin‐1 overexpressing MCF‐7 breast cancer cells and their multidrug‐resistant cell lines. Doxorubicin‐incorporated multivalent aptamer–siRNA conjugates exert promising anticancer effects, such as activation of caspase‐3/7 and decrease of cell viability, on multidrug‐resistant cancer cells because of their high intracellular uptake efficiency. Thus, this delivery system is an efficient tool for combination oncotherapy with chemotherapeutics and nucleic acid drugs to overcome multidrug resistance.
Intermediate filaments constitute a class of biopolymers whose function is still poorly understood. One example for such intermediate filaments is given by neurofilaments, large macromolecules that fill the axon of neurons. Here, reconstituted networks of purified porcine neurofilaments are studied and the diffusion behavior of different nanoparticles in the biopolymer network is evaluated. A strong dependence of particle diffusion on the charge state of the particles, and – for liposomes – also on the fatty acid configuration of lipids is observed. The results suggest that both electrostatic and hydrophobic interactions contribute to nanoparticle trapping in neurofilament networks, and that the latter is enabled by lipids with an inverted cone geometry which grant access to the hydrophobic core of the liposome shell.
Antimicrobial polymeric films that are both mechanically robust and function renewable would have broad technological implications for areas ranging from medical safety and bioengineering to foods industry; however, creating such materials has proven extremely challenging. Here, a novel strategy is reported to create high‐strength N‐halamine incorporated poly(vinyl alcohol‐co‐ethylene) films (HAF films) with renewable antimicrobial activity by combining melt radical graft polymerization and reactive extrusion technique. The approach allows here the intrinsically rechargeable N‐halamine moieties to be covalently incorporated into polymeric films with high biocidal activity and durability. The resulting HAF films exhibit integrated properties of robust mechanical strength, high transparency, rechargeable chlorination capability (>300 ppm), and long‐term durability, which can effectively offer 3–5 logs CFU reduction against typical pathogenic bacterium Escherichia coli within a short contact time of 1 h, even at high organism conditions. The successful synthesis of HAF films also provides a versatile platform for exploring the applications of antimicrobial N‐halamine moieties in a self‐supporting, structurally adaptive, and function renewable form.
The development of delivery systems efficiently uptaken by cells is of due importance since sites of drug action are generally localized in subcellular compartments. Herein, naked and core–shell polymeric nanoparticles (NPs) have been produced from poly(lactic‐co‐glycolic acid)—PLGA, poly(ethylene oxide)‐b‐poly(ε‐caprolactone)—PEO‐b‐PCL, and poly(ethylene oxide)‐b‐poly(lactic acid)—PEO‐b‐PLA. The nanostructures are characterized and the cellular uptake behavior is evaluated. The data evidence that cellular uptake is enhanced as the length of the hydrophilic PEO‐stabilizing shell reduces and that high negative surface charge restricts cellular uptake. Furthermore, NPs of higher degree of hydrophobicity (PEO‐b‐PCL) are more efficiently internalized as compared to PEO‐b‐PLA NPs. Accordingly, taking into account our recent published results 1 and the findings of the current investigation, there should be a compromise regarding protein fouling and cellular uptake as resistance to nonspecific protein adsorption and enhanced cellular uptake are respectively directly and inversely related to the length of the PEO‐stabilizing shell.
Affinity‐based cell separation is label‐free and highly specific, but it is difficult to efficiently and gently release affinity‐captured cells due to the multivalent nature of cell‐material interactions. To address this challenge, we have developed a platform composed of a capture substrate and a cell‐releasing molecular trigger. The capture substrate is functionalized with a cell‐capture antibody and a coiled‐coil A . The cell‐releasing molecular trigger B ‐PEG (polyethylene glycol), a conjugate of a coiled‐coil B and polyethylene glycol, can drive efficient and gentle release of the captured cells, because A / B heterodimerization brings B ‐PEG to the substrate and PEG chains adopt extended conformations and break nearby multivalent antibody‐biomarker interactions. No enzymes or excessive shear stress are involved, and the released cells have neither external molecules attached nor endogenous cell‐surface molecules cleaved, which is critical for the viability, phenotype, and function of sensitive cells.
Microparticulate systems composed of biodegradable polymers, such as poly(d ,l ‐lactic‐co‐glycolic acid) (PLGA), are widely used for controlled release of bioactive molecules. However, the acidic microenvironment within these microparticles, as they degrade, has been reported to perturb the configuration of most encapsulated proteins. In addition, these polymer particles are also reported to suffer from unrealistically slow and incomplete release of proteins. To address these drawbacks, hollow PLGA microparticles are fabricated through a novel one‐step oil‐in‐water emulsion solvent evaporation technique, by capitalizing on the osmotic property of an osmogen. The effects of fabrication parameters on particle size and morphology, i.e., volume space of hollow cavity and shell thickness, are also studied. These hollow microparticles are subsequently loaded with bovine insulin microcrystals. It is shown that insulin release profiles can be tuned by simply changing the amount of osmogen in the formulation. At the same time, these hollow microparticles are shown to be effective in maintaining the bioactivity of the encapsulated protein.
Here, it is demonstrated that X‐ray nanotomography with Zernike phase contrast can be used for 3D imaging of cells grown on electrospun polymer scaffolds. The scaffold fibers and cells are simultaneously imaged, enabling the influence of scaffold architecture on cell location and morphology to be studied. The high resolution enables subcellular details to be revealed. The X‐ray imaging conditions were optimized to reduce scan times, making it feasible to scan multiple regions of interest in relatively large samples. An image processing procedure is presented which enables scaffold characteristics and cell location to be quantified. The procedure is demonstrated by comparing the ingrowth of cells after culture for 3 and 6 days.
Current state‐of‐the‐art management of open spina bifida defects entails an open fetal surgery approach associated with significant morbidities. In an attempt to reduce these risks and provide for an earlier minimally invasive repair, it is aimed to develop and characterize an innovative alternative using a unique reverse thermal gel. This study focuses on characterization of the physical and biological properties of the polymer and its in vivo applicability. Based on the knowledge and benchmarking, the “ideal” biomaterial should have the following characteristics: stability in amniotic fluid, limited permeability, biocompatibility, biologically functional, nontoxic, ability to support cellular functions, and in vivo applicability. The results demonstrate that the polymer possesses a unique ultrastructure, is stable in amniotic fluid, possesses limited yet predictable permeability, biocompatible with cells exposed in neural tube defects, is nontoxic, and can support cellular migration. These characteristics make it a potential novel alternative to open fetal repairs.
This paper reports the use of polyhedral oligomeric silsesquioxane (POSS)‐based copolymers to stabilize the core/shell interface for the facile fabrication of electrospun core/shell fibers. For the poly[(propylmethacryl‐heptaisobutyl‐polyhedral oligomeric silsesquioxane)‐co‐(methyl methacrylate)] (POSS‐MMA)/poly(ε‐caprolactone) (PCL) system, the bicontinuity of hybrid core/shell fibers can be tuned by controlling the phase separation of POSS‐MMA/PCL in electrospinning solutions and therefore the size of PCL‐in‐POSS‐MMA emulsion droplets. Our results demonstrate the enhanced encapsulation capacity of POSS‐MMA copolymers as shell materials. Taking advantage of the rapid advancement of POSS‐based copolymer synthesis, this study can potentially be generalized to guide the fabrication of various other POSS‐based core/shell nano‐/microstructures by using single‐nozzle electrospinning or coaxial electrospinning.
Synthesis of a cyclodextrin (CD) polyrotaxane is achieved for the first time by simultaneous free radical polymerization of isoprene, threading by CD, and stoppering by copolymerization of styrene. This reaction is performed in an eco‐friendly manner in an aqueous medium similar to classical emulsion polymerization. Threaded CD rings of the polyrotaxane are cross‐linked by hexamethylene diisocyanate, leading to highly elastic slide‐ring gels.
Solution behavior of thermo‐responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo‐responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo‐responsive block copolymer of quaternized poly(4‐vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c‐Myc oncogene are also thermo‐responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.
New macromolecules such as dendrimers are increasingly needed to drive breakthroughs in diverse areas, for example, healthcare. Here, the authors report hybrid antimicrobial dendrimers synthesized by functionalizing organometallic dendrimers with quaternary ammonium groups or 2‐mercaptobenzothiazole. The functionalization tunes the glass transition temperature and antimicrobial activities of the dendrimers. Electron paramagnetic resonance spectroscopy reveals that the dendrimers form free radicals, which have significant implications for catalysis and biology. In vitro antimicrobial assays indicate that the dendrimers are potent antimicrobial agents with activity against multidrug‐resistant pathogens such as methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus faecium as well as other microorganisms. The functionalization increases the activity, especially in the quaternary ammonium group‐functionalized dendrimers. Importantly, the activities are selective because human epidermal keratinocytes cells and BJ fibroblast cells exposed to the dendrimers are viable after 24 h.
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