Macromolecular Bioscience

Cover image for Vol. 16 Issue 7

Early View (Online Version of Record published before inclusion in an issue)

Editor-in-Chief: Kirsten Severing, Editor: Anne Pfisterer

Online ISSN: 1616-5195

Associated Title(s): Advanced Healthcare Materials, Macromolecular Chemistry and Physics, Macromolecular Materials and Engineering, Macromolecular Rapid Communications

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  1. 1 - 47
  1. Full Papers

    1. A Luteolin-Loaded Electrospun Fibrous Implantable Device for Potential Therapy of Gout Attacks

      Yi Wang, Chao Luo, Guang Yang, Xiao Wei, Dian Liu and Shaobing Zhou

      Version of Record online: 22 JUL 2016 | DOI: 10.1002/mabi.201600123

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      A biodegradable polymer composite fiber device loading with luteolin is successfully developed via an electrospinning technology. The loaded drug can be controlled release from this device by simply adjusting the blend ratio of polymers, enabling it to potentially treat gout attacks.

    2. Enzymatic Crosslinking of Polymer Conjugates is Superior over Ionic or UV Crosslinking for the On-Chip Production of Cell-Laden Microgels

      Sieger Henke, Jeroen Leijten, Evelien Kemna, Martin Neubauer, Andreas Fery, Albert van den Berg, Aart van Apeldoorn and Marcel Karperien

      Version of Record online: 21 JUL 2016 | DOI: 10.1002/mabi.201600174

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      Cell encapsulating microgels are a promising tool for drug screening and tissue engineering approaches. However, only a limited amount of biomaterials have been reported to be compatible with on-chip microgel formation. Here, on-chip fabrication of dextran-tyramine microgels has been explored and reported that these microgels possess significant advantages over commonly used biomaterials, including improved cell survival, metabolic activity, and microgel stability.

    3. Synthesis of pH-Cleavable dPG-Amines for Gene Delivery Application

      Mathias Dimde, Dirk Steinhilber, Falko Neumann, Yan Li, Florian Paulus, Nan Ma and Rainer Haag

      Version of Record online: 19 JUL 2016 | DOI: 10.1002/mabi.201600190

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      This paper describes the development of two pH-cleavable polyglycerol-amine-based nanocarriers. The benzacetal bond represents the pH-sensitive cleavage site between dendritic polyglycerol (dPG) and glycerol-based 1,2-diamines that can complex genetic material. In vitro experiments demonstrate the ability of the cleavable dPG-amine to transfect HeLa cells with GFP-DNA, which resulted in cell-compatible cleavage products.

  2. Feature Articles

    1. Physico-Chemical Strategies to Enhance Stability and Drug Retention of Polymeric Micelles for Tumor-Targeted Drug Delivery

      Yang Shi, Twan Lammers, Gert Storm and Wim E. Hennink

      Version of Record online: 14 JUL 2016 | DOI: 10.1002/mabi.201600160

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      In this review, the most promising physico-chemical approaches to enhance polymeric micelle stability and drug retention are described, and how these strategies contribute to polymeric micelles with promising therapeutic efficacy in animal models, paving the way for clinical translation, is summarized.

  3. Full Papers

    1. Intracellular Delivery and Triggered Release of DNA Using Biodegradable Poly(2-hydroxypropylene imine)s Containing Cystamine Units

      Alma Bockuviene, Kristina Slavuckyte, Ausvydas Vareikis, Sarunas Zigmantas, Lolita Zaliauskiene and Ricardas Makuska

      Version of Record online: 14 JUL 2016 | DOI: 10.1002/mabi.201600155

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      Novel polymers containing different amounts of disulfide linkages. Polymers are able to break down and release DNA following the treatment with reducing agent 1,4-dithiothreitol. Downstream application of poly(2-hydroxypropylene imines) containing segments of cystamine transfected cells for RNA purification shows that RNA yield is not affected even after the double transfection suggesting that these polymers could be great candidates for in vitro and in vivo transfection.

    2. Microbial Cells with a Fe3O4 Doped Hydrogel Extracellular Matrix: Manipulation of Living Cells by Magnetic Stimulus

      Xudian Shi, Zhijun Shi, Daming Wang, Muhammad Wajid Ullah and Guang Yang

      Version of Record online: 14 JUL 2016 | DOI: 10.1002/mabi.201600143

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      The creation of artificial extracellular matrix (ECM) for microbial cells using alginate hydrogels can maintain the cell activity and metabolic level. After Fe3O4 nanoparticles are doped into the matrix, the treated cells display high magnetic responsiveness in an external magnetic field and thus are expected to work as nano/micro robots. This can be easily done by manipulating the ‘robots' to form micro-scaled patterns on a magnetic template with a specific design.

    3. Extending Time Profile of Morphine-Induced Analgesia Using a Chitosan-Based Molecular Imprinted Polymer Nanogel

      Marjan Hassanzadeh, Mousa Ghaemy and Shamseddin Ahmadi

      Version of Record online: 14 JUL 2016 | DOI: 10.1002/mabi.201600177

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      Chitosan-based molecular imprinted polymer (CS-MIP) nanogel is prepared in the presence of morphine template. This new drug vehicle is to extend duration of morphine analgesic effect in mice. The results suggest that CS-MIP nanogel can be a possible strategy as morphine carrier for controlled release and extension of its analgesic efficacy.

    4. Redox Reducible and Hydrolytically Degradable PEG–PLA Elastomers as Biomaterial for Temporary Drug-Eluting Medical Devices

      Simona Rupnik, Sytze Buwalda, Stéphane Dejean, Audrey Bethry, Xavier Garric, Jean Coudane and Benjamin Nottelet

      Version of Record online: 5 JUL 2016 | DOI: 10.1002/mabi.201600132

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      Degradable elastomers for soft tissue-related medical devices are proposed. These poly(lactic acid)–poly(ethylene glycol)-based biomaterials have mechanical properties suitable for soft tissue applications, and feature a bimodal redox/hydrolytic degradation. Besides, they offer drug loading and drug release ability, as well as a tunable cell compatibility that makes them anti- or proproliferative biomaterials.

    5. Hyaluronic Acid Derivative with Improved Versatility for Processing and Biological Functionalization

      Fabio S. Palumbo, Stefano Agnello, Calogero Fiorica, Giovanna Pitarresi, Roberto Puleio, Anna Tamburello, Ruggero Loria and Gaetano Giammona

      Version of Record online: 5 JUL 2016 | DOI: 10.1002/mabi.201600114

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      Hyaluronic acid derivative physically assembled into porous scaffold, versatile for bio effectors loading and tethering. Physicochemical properties of derivative allow production of scaffolds without chemical crosslinking. Hydrophobic coils allow loading of dexamethasone and its sustained release. Chemical versatility of this hyaluronic acid derivative is exploited for arginylglycylaspartic acid (RGD) tethering. Improvement of chondrocyte adhesion and maintenance of phenotype is obtained.

    6. Synthesis of Polyester Dendritic Scaffolds for Biomedical Applications

      Lukas P. Sadowski, Patricia E. Edem, John F. Valliant and Alex Adronov

      Version of Record online: 4 JUL 2016 | DOI: 10.1002/mabi.201600154

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      Dendritic scaffolds that can be site-specifically radiolabeled with 99mTc at their core, and efficiently decorated with multiple targeting ligands at their periphery are reported. These structures are functionalized with acyloxymethyl ketones as targeting ligands for cathepsin B.

  4. Communications

    1. Nucleobase-Functionalized Supramolecular Micelles with Tunable Physical Properties for Efficient Controlled Drug Release

      Chih-Chia Cheng, I-Hong Lin, Jem-Kun Chen, Zhi-Sheng Liao, Jyun-Jie Huang, Duu-Jong Lee and Zhong Xin

      Version of Record online: 4 JUL 2016 | DOI: 10.1002/mabi.201600189

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      A new series of supramolecular polymer micelles containing complementary nucleobase molecular recognition exhibits excellent drug-loading and pH-triggered drug-release ability in aqueous solution due to the presence of physical cross-links.

  5. Full Papers

    1. Fibrin Association at Hybrid Biointerfaces Made of Clot-Binding Peptides and Polythiophene

      A. Puiggalí-Jou, Luis J. del Valle, Elaine Armelin and Carlos Alemán

      Version of Record online: 1 JUL 2016 | DOI: 10.1002/mabi.201600128

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      The properties as biointerfaces of biocomposites formed by the conjugation of poly(3,4-ethylenedioxythiophene) and CREKA or CR(NMe)EKA peptides (where Glu has been replaced by N-methyl-Glu in the latter) have been compared. Analyses have been focused on the influence of such peptides in the formation of specific interactions with fibrin and the selective attachment of metastatic cells with respect to normal cells.

    2. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer

      Keishiro Tomoda, Yu Tong Tam, Hyunah Cho, Darya Buehler, Kevin R. Kozak and Glen S. Kwon

      Version of Record online: 1 JUL 2016 | DOI: 10.1002/mabi.201600194

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      Triolimus, a multi-drug loaded PEG-b-PLA polymeric micelle containing paclitaxel, 17-allylamino-17-demethoxygeldanamycin and rapamycin shows significant radiosensitization toward cancer cells. Pretreatment of Triolimus before fractionated radiation leads to tumor control. Triolimus in combination with radiation therapy is merited.

    3. Bio-Inspired Coating Strategies for the Immobilization of Polymyxins to Generate Contact-Killing Surfaces

      Diana Alves and Maria Olívia Pereira

      Version of Record online: 27 JUN 2016 | DOI: 10.1002/mabi.201600122

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      Immobilization of polymyxins onto polydimethylsiloxane, using dopamine-based coating strategies, renders the surfaces with antimicrobial properties, without causing any harm to mammalian cells. Furthermore, cells adhered to these surfaces exhibit the same susceptibility pattern as cells adhered to unmodified surfaces, which suggests no resistance development. Polymyxins immobilization holds, therefore, a great potential as an additional antimicrobial functionality in the design of biomaterials.

    4. Enhanced Targeted Delivery of Cyclodextrin-Based Supermolecules by Core–Shell Nanocapsules for Magnetothermal Chemotherapy

      I-Chieh Lin, Jen-Hung Fang, Chien-Ting Lin, Shou-Yuan Sung, Yu-Lin Su and Shang-Hsiu Hu

      Version of Record online: 21 JUN 2016 | DOI: 10.1002/mabi.201600131

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      The double emulsion capsules can improve the accumulation of drug-incorporated targeted-supermolecules at targeted tumor site through an external magnetic field (high-frequency magnetic field) stimulus. Targeted thermal chemotherapy of supermolecules involves an internalization of large amounts of drugs to cancer cell, which is actuated by cancer-cell binding proteins on supermolecules, all contributing to cell kill.

  6. Features

    1. How to Tackle the Challenge of siRNA Delivery with Sequence-Defined Oligoamino Amides

      Sören Reinhard and Ernst Wagner

      Version of Record online: 21 JUN 2016 | DOI: 10.1002/mabi.201600152

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      Polyplexes form through electrostatic interaction of negatively charged siRNA and multifunctional sequence-defined oligocations. Shielded and targeted polyplexes are taken up via receptor-mediated endocytosis. An increased density of positive charges upon endosomal acidification leads to an influx of chloride and water, resulting in osmotic pressurizing. Lytic domains further promote pH-triggered vesicle burst and thus the release of siRNA into the cytosol.

  7. Full Papers

    1. Near Infrared Dye Conjugated Nanogels for Combined Photodynamic and Photothermal Therapies

      Mazdak Asadian-Birjand, Julian Bergueiro, Stefanie Wedepohl and Marcelo Calderón

      Version of Record online: 14 JUN 2016 | DOI: 10.1002/mabi.201600117

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      Cyanin dye conjugated nanogels are designed and evaluated in vitro as a polyvalent platform for photothermal and photodynamic therapy. Along with their biocompatible profile, their near infrared light-to-heat transducing property, and their imaging ability, they offer possibilities for their further use as a theranostic agent in vivo.

    2. Protease-Triggered, Integrin-Targeted Cellular Uptake of Recombinant Protein Micelles

      Chen Gao, Kevin B. Vargo and Daniel A. Hammer

      Version of Record online: 10 JUN 2016 | DOI: 10.1002/mabi.201600032

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      A naturally occurring protein surfactant is genetically modified to incorporate bioactive motifs that enables controlled breast cancer cell line targeting. The recombinant protein surfactant self-assembles into nanoscale micelles in aqueous environments, exposing the bioactive motif RGDS only upon reaction with thrombin protease. The recombinant protein is a flexible model that can be precisely engineered, and offers a promising approach for cell targeting and potential drug release.

    3. Poly-l-Lactic Acid Nanofiber–Polyamidoamine Hydrogel Composites: Preparation, Properties, and Preliminary Evaluation as Scaffolds for Human Pluripotent Stem Cell Culturing

      Chiara Gualandi, Nora Bloise, Nicolò Mauro, Paolo Ferruti, Amedea Manfredi, Maurilio Sampaolesi, Anna Liguori, Romolo Laurita, Matteo Gherardi, Vittorio Colombo, Livia Visai, Maria Letizia Focarete and Elisabetta Ranucci

      Version of Record online: 10 JUN 2016 | DOI: 10.1002/mabi.201600061

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      New bioactive composites based on poly-l-lactic acid (PLLA) mats carrying surface amine groups, introduced by nitrogen plasma treatment, and AGMA1, a biocompatible polyamidoamine with RGD-mimic repeating units, are obtained. These composites absorb large amounts of water becoming translucent, soft, pliable, yet mechanically strong materials. Preliminary experiments show that the PLLA-AGMA1 composites successfully support short-term undifferentiated human pluripotent stem cell cultures.

  8. Communications

    1. Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG-Polypeptide Copolymers

      Graciela E. Negri and Timothy J. Deming

      Version of Record online: 10 JUN 2016 | DOI: 10.1002/mabi.201600136

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      Wulff-type phenylboronic acid functionalized polypeptide block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins at acidic conditions, such as found in endosomal and lysosomal compartments within cells. These new functional polypeptide copolymers are promising for further development as carriers for intracellular protein delivery.

  9. Full Papers

    1. Cytocompatible, Photoreversible, and Self-Healing Hydrogels for Regulating Bone Marrow Stromal Cell Differentiation

      Lianlian Yu, Kaige Xu, Liangpeng Ge, Wenbing Wan, Ali Darabi, Malcolm Xing and Wen Zhong

      Version of Record online: 9 JUN 2016 | DOI: 10.1002/mabi.201500457

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      Novel photostimulated self-healing and biocompatible polyacrylamide hydrogels are reported. A coumarin crosslinker endows superb self-healing capacity upon exposure to 280 and 365 nm light. A polyamidoamine crosslinker enhances cell compatibility. The hydrogels induce a regular cellular pattern and regulate osteogenic differentiation of bone marrow stromal cell.

    2. Tuning the Surface of Nanoparticles: Impact of Poly(2-ethyl-2-oxazoline) on Protein Adsorption in Serum and Cellular Uptake

      Olga Koshkina, Dana Westmeier, Thomas Lang, Christoph Bantz, Angelina Hahlbrock, Christian Würth, Ute Resch-Genger, Ulrike Braun, Raphael Thiermann, Christoph Weise, Murat Eravci, Benjamin Mohr, Helmut Schlaad, Roland H. Stauber, Dominic Docter, Annabelle Bertin and Michael Maskos

      Version of Record online: 9 JUN 2016 | DOI: 10.1002/mabi.201600074

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      While biomedical applications of nanoparticles are steadily increasing, undesirable adsorption of biomolecules in biological fluids represents one major challenge. Here, biocompatible poly(2-ethyl-2-oxazoline) (PEtOx) for the stealth modification of nanoparticles is probed. Comparing protein adsorption and cellular uptake of PEtOxylated nanoparticles to other modifications, it is demonstrated that PEtOx is at least as effective as the gold standard poly(ethylene glycol).

    3. Protection of Vine Plants against Esca Disease by Breathable Electrospun Antifungal Nonwovens

      Viola Buchholz, Melanie Molnar, Hui Wang, Steffen Reich, Seema Agarwal, Michael Fischer and Andreas Greiner

      Version of Record online: 9 JUN 2016 | DOI: 10.1002/mabi.201600118

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      Electrospun nonwovens with antifungal additives for active blocking of spores to prevent Esca infections of vine plants are presented. The disease leads to poor vine crops or to a sudden dieback of the vine plants. The combination of antifungal properties and breathable electrospun nonwovens could be a suitable way to inhibit the spreading of the disease.

    4. Poly(1,3-propylene sebacate) and Poly(sebacoyl diglyceride): A Pair of Potential Polymers for the Proliferation and Differentiation of Retinal Progenitor Cells

      Ni Ni, Jing Ji, Shuo Chen, Dandan Zhang, Zi Wang, Bingqiao Shen, Chunyu Guo, Yi Zhang, Shaofei Wang, Xianqun Fan, Zhengwei You, Min Luo and Ping Gu

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600058

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      This study investigates the effects of poly(sebacoyl diglyceride) (PSeD) and its counterpart poly(1,3-propylene sebacate) (PPS) on retinal progenitor cell (RPC) proliferation, differentiation, and migration. Our results show that PPS significantly enhances RPC proliferation, whereas PSeD largely promotes RPCs' differentiation toward retinal neurons with superior migration capacity, indicating that PPS and PSeD may have potential applications in future retinal cell-replacement therapies.

    5. Differentiation of Human Mesenchymal Stem Cells Toward Quality Cartilage Using Fibrinogen-Based Nanofibers

      Jeremy Forget, Firas Awaja, Dencho Gugutkov, Juhan Gustavsson, Gloria Gallego Ferrer, Tatiana Coelho-Sampaio, Camila Hochman-Mendez, Manuel Salmeron-Sánchez and George Altankov

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600080

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      The illustration of the preparation steps for the 2D and 3D constructs, including: (1) production of samples via deposition of random or aligned electrospun nanofibers on gel slices, (2) seeding of ADSCs and their propagation up to confluency, (3) assembly of the constructs, either in 2D (single slides) or 3D (sandwich-like) configuration, and (4) cultivation of living construct in chondrogenic differentiation medium.

    6. Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns

      Jianmei Chen, Zongguang Liu, Maohua Chen, Hong Zhang and Xiaohong Li

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600108

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      A pH conversion process has been initially developed to prepare electrospun gelatin fibers cross-linked in situ with oxidized alginate and simultaneously load gentamicin sulfate and hydrophobic ciprofloxacin into fibers. The rapid release of gentamicin and extended release of ciprofloxacin from fibers accelerate the wound healing process through controlling the bacteria infection in the deep burn wounds.

    7. Switching the Stiffness of Polyelectrolyte Assembly by Light to Control Behavior of Supported Cells

      Sviatlana A. Ulasevich, Nadzeya Brezhneva, Yulia Zhukova, Helmuth Möhwald, Peter Fratzl, Felix H. Schacher, Dmitry V. Sviridov, Daria V. Andreeva and Ekaterina V. Skorb

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600127

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      Photocatalytic reactions on titanium dioxide in response to visible light irradiation are used to regulate polyelectrolyte block copolymer micelles assembled thin film. Irradiation results in change of film height, stiffness. Film can be switched in response to local irradiation. Preosteoblasts migrate toward stiffer side of the substrates.

    8. Tuning the Selectivity of Biodegradable Antimicrobial Cationic Polycarbonates by Exchanging the Counter-Anion

      Mehmet Isik, Jeremy P. K. Tan, Robert J. Ono, Ana Sanchez-Sanchez, David Mecerreyes, Yi Yan Yang, James L. Hedrick and Haritz Sardon

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600090

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      A series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter-anions on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion.

  10. Communications

    1. Finely Tuned Thermo-Responsive Block Copolymer Micelles for Photothermal Effect-Triggered Efficient Cellular Internalization

      Mingming Huang, Hui Li, Wendong Ke, Junjie Li, Chengai Zhao and Zhishen Ge

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600119

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      Amphiphilic block copolymer micelles with finely tuned thermo-responsive coronas are constructed for high-efficiency co-delivery of doxorubicin and indocyanine green, which show photothermal effect-triggered efficient cellular uptake upon near-infrared light exposure. The design represents a facile strategy to achieve efficient cellular internalization of stealthy drug delivery systems in a spatiotemporally controlled manner.

  11. Full Papers

    1. Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing

      Cheol Am Hong and Yoon Sung Nam

      Version of Record online: 8 JUN 2016 | DOI: 10.1002/mabi.201600137

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      A single-stranded nick in an siRNA duplex provides enhanced structural flexibility in engineered siRNA nanostructures. Dimeric nicked siRNA conjugates can strongly interact with conventional cationic carriers to generate compact nanoparticles capable of facilitating cellular uptake due to their high charge density and structural flexibility. The resultant complexes exhibit efficient polymeric condensations and gene silencing efficiencies compared with nonnicked siRNA conjugates.

    2. Fast-Track, One-Step E. coli Detection: A Miniaturized Hydrogel Array Permits Specific Direct PCR and DNA Hybridization while Amplification

      Antje Beyer, Sibyll Pollok, Anne Rudloff, Dana Cialla-May, Karina Weber and Jürgen Popp

      Version of Record online: 25 MAY 2016 | DOI: 10.1002/mabi.201600098

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      This work presents a timesaving combined 3D in gel polymerase chain reaction (PCR)/hybridization protocol for bacteria detection concomitant with an easy hydrogel chip fabrication. The isolated bacterial cells and the hydrogel chip are added directly in the PCR tube containing the required PCR components. During the ongoing specific PCR, deoxyribonucleic acid amplicons binds to gel immobilized capture probes and the fluorescence signal is generated already during the amplification process.

    3. Gelatin—Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation

      Sara Poveda-Reyes, Vladimira Moulisova, Esther Sanmartín-Masiá, Luis Quintanilla-Sierra, Manuel Salmerón-Sánchez and Gloria Gallego Ferrer

      Version of Record online: 23 MAY 2016 | DOI: 10.1002/mabi.201500469

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      Injectable gelatin hyaluronic acid (HA) mixtures are synthesized to modulate matrix stiffness. The addition of small amounts of HA to gelatin significantly reduces hydrogel shrinking after cell encapsulation. Hydrogel stiffness counterbalances traction forces of cells, promoting cell differentiation.

    4. Polydopamine-Mediated Immobilization of Alginate Lyase to Prevent P. aeruginosa Adhesion

      Diana Alves, Tadas Sileika, Phillip B. Messersmith and Maria Olívia Pereira

      Version of Record online: 19 MAY 2016 | DOI: 10.1002/mabi.201600077

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      Immobilization of alginate lyase onto polycarbonate surfaces, using a dopamine-based coating strategy, renders the surfaces with the ability to prevent Pseudomonas aeruginosa adhesion, regardless of its mucoid or non-mucoid phenotype. This ability is not compromised by enzyme's heat denaturation, suggesting a catalysis-independent performance. Further studies to more comprehensively understand its mechanism of anti-adhesive action should, therefore, be performed.

    5. FRET Imaging of Enzyme-Responsive HPMA Copolymer Conjugate

      Rui Zhang, Jiyuan Yang, D. Christopher Radford, Yixin Fang and Jindřich Kopeček

      Version of Record online: 19 MAY 2016 | DOI: 10.1002/mabi.201600125

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      Cy5/Cy7-paired fluorescence resonance energy transfer (FRET) is applied to investigate the enzyme-responsive payload release in a N-(2-hydroxypropyl)methacrylamide copolymer-based drug delivery system. Upon exposure to lysosomal enzymes, the model drug Cy7 is cleaved, resulting in the loss of FRET signal. The enzyme response is visualized at the cell, tissue, and whole-body levels, indicating an effective release of payload in tumor cells.

  12. Reviews

    1. Mechanisms for Imparting Conductivity to Nonconductive Polymeric Biomaterials

      Alexander J. Patton, Laura A. Poole-Warren and Rylie A. Green

      Version of Record online: 18 MAY 2016 | DOI: 10.1002/mabi.201600057

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      There is a need for soft, biocompatible materials to support regeneration, stimulation, and recording of excitable tissue activity. This review analyzes the key approaches used to fabricate soft, conductive polymers including: coating a bulk polymer with a conductive component, dispersion of conductive inclusions through a polymer, and in situ growth of a conductive network within a polymer matrix.

  13. Full Papers

    1. Polymerizing Insulin with Photocleavable Linkers to Make Light-Sensitive Macropolymer Depot Materials

      Bhagyesh R. Sarode, Piyush K. Jain and Simon H. Friedman

      Version of Record online: 12 MAY 2016 | DOI: 10.1002/mabi.201500471

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      To make highly efficient light-activated depots of insulin, insulin itself has been used as a monomer during click-driven polymerizations. The resultant materials have the key desired properties including high insulin density, insolubility prior to irradiation and release of native insulin in response to light.

    2. You have full text access to this OnlineOpen article
      Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes

      Helena Henke, Kushtrim Kryeziu, Jelena Banfić, Sarah Theiner, Wilfried Körner, Oliver Brüggemann, Walter Berger, Bernhard K. Keppler, Petra Heffeter and Ian Teasdale

      Version of Record online: 12 MAY 2016 | DOI: 10.1002/mabi.201600035

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      Two monofunctionalized platinum(IV) complexes are conjugated to degradable poly(organo)phosphazenes to give soluble macromolecular prodrugs designed to undergo rapid, triggered intracellular release from the carrier and simultaneous reduction to the active, cytotoxic platinum(II) species. The preparation of the conjugates, as well as their in vitro and in vivo behavior, is reported.

    3. Poly(3,4-ethylenedioxythiophene):GlycosAminoGlycan Aqueous Dispersions: Toward Electrically Conductive Bioactive Materials for Neural Interfaces

      Daniele Mantione, Isabel del Agua, Wandert Schaafsma, Javier Diez-Garcia, Begona Castro, Haritz Sardon and David Mecerreyes

      Version of Record online: 11 MAY 2016 | DOI: 10.1002/mabi.201600059

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      Poly(3,4-ethylenedioxythiophene):GlycosAminoGlycan (PEDOT:GAG) dispersion are easily synthesized in water via oxidative chemical polymerization. The conductive materials are bio-tested using SH-SY5Y and CCF-STTG1 cell lines and with ATP, Ca2+, and H2O2. PEDOT/GAGs results more biotolerated than the commercial PEDOT/poly(styrene sulfonate) dispersion and have a pronounced anti-inflammatory effect. These materials can be used in all the possible situations when there is contact in between electronic circuits and living tissues.

    4. Ex Vivo and In Vitro Studies on the Cytotoxicity and Immunomodulative Properties of Poly(2-isopropenyl-2-oxazoline) as a New Type of Biomedical Polymer

      Zuzana Kroneková, Marcel Mikulec, Nadežda Petrenčíková, Ema Paulovičová, Lucia Paulovičová, Viera Jančinová, Radomír Nosál', Palem S. Reddy, Ganesh D. Shimoga, Dušan Chorvát Jr. and Juraj Kronek

      Version of Record online: 6 MAY 2016 | DOI: 10.1002/mabi.201600016

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      Poly(2-isopropenyl-2-oxazoline) is a promising functional polymer for a variety of biomedical applications. Addition reactions with different compounds containing a carboxylic group enable the functionalization of the polymer with fluorescent dyes or biomolecules. In vitro cytotoxicity, an ex vivo cell proliferation assay, and a colocalization study are used to demonstrate that poly(2-isopropenyl-2-oxazoline) is a biocompatible material suitable for biomedical applications.

  14. Communications

    1. Amino Acid Based Hydrogels with Dual Responsiveness for Oral Drug Delivery

      Shiqi Wang, Xiaoxue Liu, Ignacio J. Villar-Garcia and Rongjun Chen

      Version of Record online: 6 MAY 2016 | DOI: 10.1002/mabi.201600078

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      Hydrogels with dual responsiveness are prepared by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) coupling of pH-responsive anionic pseudo-peptides as backbones and disulfide-containing l-cystine dimethyl ester as crosslinkers. These hydrogels show high loading efficiency, rapid but complete triggered-release and good biocompatibility, thus having potential applications for oral delivery.

  15. Full Papers

    1. A Silk Fibroin and Peptide Amphiphile-Based Co-Culture Model for Osteochondral Tissue Engineering

      Soner Çakmak, Anıl S. Çakmak, David L. Kaplan and Menemşe Gümüşderelioğlu

      Version of Record online: 3 MAY 2016 | DOI: 10.1002/mabi.201600013

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      New biomaterials with the properties of both bone and cartilage extracellular matrices (ECM) should be designed and used with co-culture systems to address clinically applicable osteochondral constructs. Herein, a co-culture model based on a trilayered silk fibroin and peptide amphiphile (PA) scaffolds to achieve cartilage and bone tissues in a single system is developed.

    2. Supramolecular Hydrogel from Nanoparticles and Cyclodextrins for Local and Sustained Nanoparticle Delivery

      Shuxin Xu, Li Yin, Yuzhang Xiang, Hongzhang Deng, Liandong Deng, Hongxia Fan, Hua Tang, Jianhua Zhang and Anjie Dong

      Version of Record online: 23 APR 2016 | DOI: 10.1002/mabi.201600076

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      Supramolecular hydrogel mPECT NP/α-CDgel composed of polymer nanoparticles dispersion with high solid content (≤20% W/V) and α-CD are constructed. mPECT NP/α-CDgel can general release discrete nanoparticles of ≈50 nm lasting for more than 3 weeks in situ. The present hydrogel system can anchor a large amount of nanoparticles in situ, providing sustained and targeted nanoparticles delivery.

    3. Low Molecular Weight PEI-Based Vectors via Acid-Labile Ortho Ester Linkage for Improved Gene Delivery

      Lei Zhang, Min Yu, Jun Wang, Rupei Tang, Guoqing Yan, Weijing Yao and Xin Wang

      Version of Record online: 23 APR 2016 | DOI: 10.1002/mabi.201600071

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      Polycationic vectors (POEIs) have been synthesized via Michael addition from LMW PEI and acid-labile ortho ester linkage with terminal acrylates (OEAc). The formed POEIs/pDNA complexes can make a quick degradation-response to mildly acidic pHs, consequently facilitating endosomal escape and potentiating improved gene transfection in vitro, while maintaining low cytotoxicity.

    4. In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo-Forming Hydrogel

      Ja Yong Jang, Seung Hun Park, Ji Hoon Park, Bo Keun Lee, Jeong-Ho Yun, Bong Lee, Jae Ho Kim, Byoung Hyun Min and Moon Suk Kim

      Version of Record online: 14 APR 2016 | DOI: 10.1002/mabi.201600001

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      Human dental pulp stem cells for bone tissue engineering using in vivo-forming hydrogel: Human dental pulp stem cells (hDPSCs) are easily harvested from extracted teeth and can successfully differentiate into osteogenic cells in in vivo-forming hydrogel. This study demonstrates that hDPSCs can be acted as an excellent cell source in bone tissue engineering using in vivo-forming hydrogel.

    5. Virtual Screening of Receptor Sites for Molecularly Imprinted Polymers

      Ferdia Bates, María Concepción Cela-Pérez, Kal Karim, Sergey Piletsky and José Manuel López-Vilariño

      Version of Record online: 14 APR 2016 | DOI: 10.1002/mabi.201500461

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      A novel method for “virtual molecular imprinting” and evaluation of the resulting receptor for docking specificity and affinity: the greater degree of ab initio insight that this technique provides to the scientist regarding receptor affinity and design can greatly reduce the workload and waste production, thus creating a more efficient and greener laboratory.

    6. Scaffolds of Hyaluronic Acid–Poly(Ethyl Acrylate) Interpenetrating Networks: Characterization and In Vitro Studies

      E. Rodríguez-Pérez, A. Lloret Compañ, M. Monleón Pradas and C. Martínez-Ramos

      Version of Record online: 13 APR 2016 | DOI: 10.1002/mabi.201600028

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      Interpenetrating networks of hyaluronic acid (HA) and poly(ethyl acrylate) (PEA) are prepared in the shape of porous scaffolds through a template-leaching technique; combining properties of these two materials. Both physicochemical and biological responses of these interpenetrating polymeric network scaffolds are studied, including their cytotoxicity and their effects in cell proliferation and attachment; comparing them to those of HA and PEA porous single-network scaffolds.

    7. Polymeric Nanogels with Tailorable Degradation Behavior

      Yinan Chen, Mies J. van Steenbergen, Dandan Li, Joep B. van de Dikkenberg, Twan Lammers, Cornelus F. van Nostrum, Josbert M. Metselaar and Wim E. Hennink

      Version of Record online: 13 APR 2016 | DOI: 10.1002/mabi.201600031

      Thumbnail image of graphical abstract

      Two polymers (pHPMAm-Gly-HEMAm and pHEMAm-Gly-HEMAm) with different degrees of substitution (DS) are synthesized, and used for preparation of nanogels. In vitro degradation studies under physiological conditions demonstrate that pHEMAm-Gly-HEMAm nanogels degrade faster than pHPMAm-Gly-HEMA nanogels. The release of a loaded macromolecular model drug is controlled by degradation of nanogels.

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