Macromolecular Bioscience

Cover image for Vol. 15 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. Feature Articles

    1. Biofunctional Materials Based on Amino Cellulose Derivatives – A Nanobiotechnological Concept

      Thomas Heinze, Melanie Siebert, Peter Berlin and Andreas Koschella

      Article first published online: 30 JUL 2015 | DOI: 10.1002/mabi.201500184

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      Amino cellulose derivatives simply available by nucleophilic displacement reactions of tosyl cellulose with a broad variety of amines possess an extraordinary ability for self-assembling. Nanocomposites and monolayers may be formed on various substrates. For example, the modified surfaces are efficient carriers for (bio) functional molecules yielding efficient biosensors.

  2. Communications

    1. Anti-Resorptive Functions of Poly(ethylene sodium phosphate) on Human Osteoclasts

      Sujit Kootala, Masahiro Tokunaga, Jöns Hilborn and Yasuhiko Iwasaki

      Article first published online: 29 JUL 2015 | DOI: 10.1002/mabi.201500166

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      The effect of poly(ethylene sodium phosphate) (PEP · Na) on human osteoclasts is studied. PEP · Na exhibits excellent biocompatibility with osteoblasts, whereas the polymer effectively reduces the adhesion of osteoclasts adhered on bone slices. This is the first report to describe the possibility of using polyphosphoesters for selective inhibition of osteoclast adhesion and function.

    2. Anti-Bioadhesive Coating Based on Easy to Make Pseudozwitterionic RAFT Block Copolymers for Blood-Contacting Applications

      Sabrina Nehache, Chin-Cheng Yeh, Mona Semsarilar, André Deratani, Yung Chang and Damien Quemener

      Article first published online: 29 JUL 2015 | DOI: 10.1002/mabi.201500185

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      Well-defined pseudozwitterionic diblock copolymers are synthesized using RAFT chemistry. These charged polymers are then used to prepare anti-bioadhesion surfaces that could be used in blood-contact devices. It is demonstrated that such coatings prevent blood protein adsorption to the polymer modified surfaces.

  3. Full Papers

    1. Bioreducible Poly-l-Lysine–Poly[HPMA] Block Copolymers Obtained by RAFT-Polymerization as Efficient Polyplex-Transfection Reagents

      Kristof Tappertzhofen, Simone Beck, Evelyn Montermann, David Huesmann, Matthias Barz, Kaloian Koynov, Matthias Bros and Rudolf Zentel

      Article first published online: 29 JUL 2015 | DOI: 10.1002/mabi.201500212

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      Polylysine-S-S-b-poly[N-(2-hydroxypropyl) methacrylamide] (p[HPMA]) copolymers with a bioreducible disulfide group can be obtained by RAFT polymerization of a macromolecular disulfide chain transfer agent (CTA). Polyplex formation with pDNA leads to increased transfection efficiencies compared to non disulfide containing block copolymers.

    2. N-(2-Hydroxypropyl)methacrylamide Copolymer–Drug Conjugates for Combination Chemotherapy of Acute Myeloid Leukemia

      Rui Zhang, Jiyuan Yang, Yan Zhou, Paul J. Shami and Jindřich Kopeček

      Article first published online: 29 JUL 2015 | DOI: 10.1002/mabi.201500193

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      Four different drugs, including cytarabine, daunorubicin, GDC-0980, and JS-K, are used for two-drug combination treatment against acute myeloid leukemia. Combining cytarabine with GDC-0980 shows the strongest synergistism. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine/GDC-0980 conjugates are synthesized. They also hve potent cytotoxicity and strong synergstism in combination.

    3. Exploring the Properties of Genetically Engineered Silk-Elastin-Like Protein Films

      Raul Machado, André da Costa, Vitor Sencadas, Ana Margarida Pereira, Tony Collins, José Carlos Rodríguez-Cabello, Senentxu Lanceros-Méndez and Margarida Casal

      Article first published online: 27 JUL 2015 | DOI: 10.1002/mabi.201500132

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      Free standing films of a genetically engineered silk-elastin-like protein are prepared by solvent casting using water and formic acid as solvents. The films are exposed to methanol-saturated air to induce the formation of aggregated β-strands and extensively characterized for their properties. Results indicate that the films are electrically insulating with excellent optical clarity and mechanical properties, depending of the post-treatment and glycerol content.

  4. Communications

    1. Orthotopic Osteogenecity Enhanced by a Porous Gelatin Sponge in a Critical-Sized Rat Calvaria Defect

      Naofumi Kanda, Takahisa Anada, Takuto Handa, Kazuhito Kobayashi, Yushi Ezoe, Tetsu Takahashi and Osamu Suzuki

      Article first published online: 22 JUL 2015 | DOI: 10.1002/mabi.201500191

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      Preparation of gelatin disks for bone regeneration: this study is designed to investigate whether a gelatin sponge with a specific porous structure exhibits orthotopic osteogenecity in critical-sized rat calvarial defects. The results provide the findings that a Gel sponge is capable of inducing new bone formation orthotopically, if the scaffold has a specific porous structure.

  5. Full Papers

    1. Study on Self-Assembled Well-Defined PEG Graft Copolymers as Efficient Drug-Loaded Nanoparticles for Anti-Inflammatory Therapy

      Paulina Maksym-Bębenek and Dorota Neugebauer

      Article first published online: 22 JUL 2015 | DOI: 10.1002/mabi.201500189

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      Hydroxy-functional PEG graft polymethacrylates are designed as functional nanocarriers. The cumulative influence of hydrophilic/hydrophobic balance, degree of grafting, length of side chains and backbone, on micellization, drug loading and release profiles is demonstrated.

    2. Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood–Brain Barrier In Vitro

      Maria Gregori, Daniela Bertani, Emanuela Cazzaniga, Antonina Orlando, Michele Mauri, Alberto Bianchi, Francesca Re, Silvia Sesana, Stefania Minniti, Maura Francolini, Alfredo Cagnotto, Mario Salmona, Luca Nardo, Domenico Salerno, Francesco Mantegazza, Massimo Masserini and Roberto Simonutti

      Article first published online: 21 JUL 2015 | DOI: 10.1002/mabi.201500172

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      In the search of novel drug carriers for brain drug delivery, poly(N,N-dimethylacrylamide)-b-polystyrene nanoparticles (NP) have been functionalized with a modified fragment of Apolipoprotein E (mApoE). These NP show to be uptaken and to overcome a BBB in vitro cellular model. The cytotoxicity of NP is also investigated on different cell lines, showing high biocompatibility.

  6. Communications

    1. Microfluidic Production of Alginate Hydrogel Particles for Antibody Encapsulation and Release

      Linas Mazutis, Remigijus Vasiliauskas and David A. Weitz

      Article first published online: 21 JUL 2015 | DOI: 10.1002/mabi.201500226

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      Using a microfluidic device with a characteristic flow-focusing junction that facilitates the break-up of viscous fluids into monodisperse droplets the authors produce alginate microparticles of unique biconcave shape resembling the red blood cells. They loaded alginate particles with fluorescently labeled antibodies and evaluated their release over time in different aqueous buffers and tested the biocompatibility in the whole blood sample.

    2. Synthesis and Characterization of pH-Responsive Copolypeptides Vesicles for siRNA and Chemotherapeutic Drug Co-Delivery

      Zhanrong Li, Jingguo Li, Jinsheng Huang, Junjie Zhang, Du Cheng and Xintao Shuai

      Article first published online: 17 JUL 2015 | DOI: 10.1002/mabi.201500161

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      A novel pH-sensitive polymeric vesicles based on diblock copolypeptides for anti-cancer drugs and siRNA co-delivery are described. The vesicles are stable in aqueous solutions at neutral pH and disassemble in acidic pHs. The vesicles can co-deliver DOX and siRNA inside the same cell and exhibit a pH-sensitive drug release behavior.

  7. Full Papers

    1. Neurogenesis Is Induced by Electrical Stimulation of Human Mesenchymal Stem Cells Co-Cultured With Mature Neuronal Cells

      Sang Jun Park, Ji Sun Park, Han Na Yang, Se Won Yi, Chun-Ho Kim and Keun-Hong Park

      Article first published online: 17 JUL 2015 | DOI: 10.1002/mabi.201500115

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      The effects of both electrical stimulation and co-culturing hMSCs with neuronal cells are tested. The hMSCs co-cultured with mature neuronal cells and stimulated with electrical shock show the greatest level of neurite outgrowth (>150 µm) and smaller cell body sizes. The neuronal differentiation of the adhered hMSCs onto glass cover slips with gold nanoparticles are also evaluated for their specific genes and proteins.

    2. Crosslinked Polypropylenimine Dendrimers With Bioreducible Linkages for Gene Delivery Systems and Their Reductive Degradation Behaviors

      Gyeong Jin Lee, Kitae Ryu, Kyunghwan Kim, Ji-yeong Choi and Tae-il Kim

      Article first published online: 16 JUL 2015 | DOI: 10.1002/mabi.201500141

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      Crosslinked bioreducible polypropylenimine dendrimers (PPI–CBAs) showed high stability even in reducing condition probably due to the re-crosslinking. It is thought that this may lead to additional consumption of glutathione and the following increase of intracellular reactive oxygen species according to the concentration and crosslinking degree of PPI–CBAs, finally inducing cytotoxicity by oxidative stress.

    3. Cathepsin B Imaging to Predict Quality of Engineered Cartilage

      Ji Young Yhee, Yong-Jin Kim, Ju Hee Ryu, Hong Yeol Yoon, Hyeyoun Chang, Jae Hyung Park, Hyukjin Lee, Hyon-Seok Jang, Unyong Jeong, Kwangmeyung Kim and Sun-Woong Kang

      Article first published online: 14 JUL 2015 | DOI: 10.1002/mabi.201500215

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      Cathepsin B (CB)-specific molecular imaging probe is applied to monitor the changes of CB expression in 3D cultured chondrocytes. The CB activities in two different sets of chondrocytes are comparatively analyzed using the probe, and CB molecular imaging can provide a reliable prediction for the quality of engineered cartilage in re-differentiating chondrocytes, during the formation of new cartilage tissue.

    4. Fluorescent Phosphorus Dendrimer as a Spectral Nanosensor for Macrophage Polarization and Fate Tracking in Spinal Cord Injury

      Antos Shakhbazau, Manoj Mishra, Tak-Ho Chu, Craig Brideau, Karen Cummins, Shigeki Tsutsui, Dzmitry Shcharbin, Jean-Pierre Majoral, Serge Mignani, Mireille Blanchard-Desce, Maria Bryszewska, V. Wee Yong, Peter K. Stys and Jan van Minnen

      Article first published online: 14 JUL 2015 | DOI: 10.1002/mabi.201500150

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      Fluorescent phosphorus dendrimer is readily internalized and maintained by bone marrow-derived macrophages, making it a useful cytoplasmic tracer. Sensitivity of dendrimer emission profile to the macrophage physiological status generates distinct spectral phenotypes, a feature which may offer new strategies for targeted release of therapeutic cargos, and assist in tracing macrophage plasticity in longitudinal studies in vitro and in vivo.

    5. Acid-Sensitive Nanogels for Synergistic Chemo-Photodynamic Therapy

      Xiaofei Chen, Xuemei Yao, Li Chen and Xuesi Chen

      Article first published online: 14 JUL 2015 | DOI: 10.1002/mabi.201500180

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      A novel kind of intelligent nanogels is designed, which can spatiotemporally control the release of drug (doxorubicin) and photosensitizers (porphyrins) to combine chemo-therapy and photodynamic therapy..

    6. Targeted Imaging and Chemo-Phototherapy of Brain Cancer by a Multifunctional Drug Delivery System

      Yongwei Hao, Lei Wang, Yalin Zhao, Dehui Meng, Dong Li, Haixia Li, Bingxiang Zhang, Jinjin Shi, Hongling Zhang, Zhenzhong Zhang and Yun Zhang

      Article first published online: 14 JUL 2015 | DOI: 10.1002/mabi.201500091

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      Multifunctional poly (lactide-co-glycolic acid) nanoparticles are developed by a modified oil in water single-emulsion solvent evaporation method. They could simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. Under the 808 nm laser irradiation, the glioma growth of the nude mice bearing U87MG glioma is efficiently inhibited.

    7. Visualizing the Inner Architecture of Poly(ϵ-caprolactone)-Based Biomaterials and Its Impact on Performance Optimization

      Adam J. P. Bauer, Yitian Wu, Jianzhao Liu and Bingbing Li

      Article first published online: 7 JUL 2015 | DOI: 10.1002/mabi.201500175

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      This study demonstrates the superior degradation selectivity of Candida antarctica lipase B (CALB) enzyme; when used at low concentrations, it preferentially breaks down the amorphous chains of poly(ϵ-caprolactone) (PCL) prior to its crystalline chains. Top-down dissection using this enzyme is performed on several PCL-based model systems. The spatial distribution of the amorphous compartments are precisely mapped out, which otherwise cannot be achieved.

    8. A New Hyaluronic Acid Derivative Obtained from Atom Transfer Radical Polymerization as a siRNA Vector for CD44 Receptor Tumor Targeting

      Fabio Salvatore Palumbo, Antonella Bavuso Volpe, Flavia Bongiovì, Giovanna Pitarresi and Gaetano Giammona

      Article first published online: 1 JUL 2015 | DOI: 10.1002/mabi.201500129

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      New cationic HA derivatives (HA-EDA-pDEAEMA), synthesized by atom transfer radical polymerization (ATRP) are able to complex siRNA and to form self-assembled nanosystems. In vitro studies performed on HCT 116 cell line, which over express CD44 receptor, demonstrate a receptor-mediated uptake of complexes.

    9. Multi-Layered Scaffolds for Osteochondral Tissue Engineering: In Vitro Response of Co-Cultured Human Mesenchymal Stem Cells

      Sofia Amadori, Paola Torricelli, Silvia Panzavolta, Annapaola Parrilli, Milena Fini and Adriana Bigi

      Article first published online: 30 JUN 2015 | DOI: 10.1002/mabi.201500165

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      Multi-layered, easily synthesized scaffolds made of gelatin and hydroxyapatite are able to promote chondrogenic and osteogenic differentiation of human mesenchymal stem cells.

    10. Advanced Evaluation Strategies for Protein-Imprinted Polymer Nanobeads

      Bettina Pluhar and Boris Mizaikoff

      Article first published online: 26 JUN 2015 | DOI: 10.1002/mabi.201500106

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      An analytical strategy for providing exhaustive information on the selective binding and inhibition properties of nano-MIPs. Inhibited and active pepsin, respectively, along with two other proteins were incubated to equilibrium with pepsin-imprinted nanobeads, separated from the nanobeads by centrifugation, and the remaining supernatant was analyzed via SDS-PAGE.

  8. Communications

    1. EGFP-Based Protein Nanoparticles with Cell-Penetrating Peptide for Efficient siRNA Delivery

      Xingang Guan, Xiuli Hu, Fengchao Cui, Yunqi Li, Xiabing Jing and Zhigang Xie

      Article first published online: 24 JUN 2015 | DOI: 10.1002/mabi.201500163

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      Fluorescent protein (EGFP) nanoparticles are developed and used for siRNA delivery. Protein nanoparticle can condense siRNA into stable nanoparticle/siRNA complexes, and transfect cy3-labelled siRNA into tumor cells.

  9. Full Papers

    1. Probing the Mucoadhesive Interactions Between Porcine Gastric Mucin and Some Water-Soluble Polymers

      Yasser A. Albarkah, Rebecca J. Green and Vitaliy V. Khutoryanskiy

      Article first published online: 23 JUN 2015 | DOI: 10.1002/mabi.201500158

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      This study reports the structural features of porcine gastric mucin in aqueous dispersions and its interactions with water-soluble polymers. Sonication of mucin dispersion results in disaggregation of particles. However, the interaction of mucin with poly(carboxylic acids) via hydrogen bonding causes further aggregation of its particles.

    2. Hydrolysis-Sensitive Dithiolethione Prodrug Micelles

      Urara Hasegawa, Naoya Tateishi, Hiroshi Uyama and André J. van der Vlies

      Article first published online: 23 JUN 2015 | DOI: 10.1002/mabi.201500156

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      Hydrolysis-sensitive micellar prodrugs of desmethyl anethole dithiolethione (ADTOH), a chemopreventive agent, are prepared from amphiphilic block copolymers composed of a hydrophilic poly(N-acryloyl morpholine) block and a hydrophobic block linking ADT-OH via an ester bond using glycine and isoleucine linkers. This ADT-ester approach enables to modulate the release rate of ADT-OH and thus might find potential application in cancer therapy and prevention.

    3. C-Terminal-oriented Immobilization of Enzymes Using Sortase A-mediated Technique

      Yuto Hata, Takuya Matsumoto, Tsutomu Tanaka and Akihiko Kondo

      Article first published online: 22 JUN 2015 | DOI: 10.1002/mabi.201500113

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      C-Terminal-oriented immobilization of enzymes is demonstrated by sortase A-mediated technique. Although C-terminal-oriented immobilization of enzymes does not provide an improvement of the resistance to pH and thermotolerance, enzymes immobilized by this technique show improved activity and reusability compared to chemically immobilized enzymes. This study indicates that oriented immobilization of enzymes by sortase A may improve the feasibility of industrial utilization of enzymes.

    4. Mussel-Inspired Modification of Nanofibers for REST siRNA Delivery: Understanding the Effects of Gene-Silencing and Substrate Topography on Human Mesenchymal Stem Cell Neuronal Commitment

      Wei Ching Low, Pim-On Rujitanaroj, Dong-Keun Lee, Jinghao Kuang, Phillip B. Messersmith, Jerry Kok Yen Chan and Sing Yian Chew

      Article first published online: 19 JUN 2015 | DOI: 10.1002/mabi.201500101

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      DOPA-melanin (DM) coated nanofibers were functionalized with siRNA to induce REST silencing in mesenchymal stem cells (MSCs) for neuronal differentiation. DM modification enhanced the siRNA loading, release kinetics, and REST knockdown efficiency. Under non-specific differentiation condition, the synergistic effects of REST silencing and nanofiber topography improved MSCs neuronal commitment. Such nanofiber-mediated gene silencing platform may find promising applications in vivo.

    5. Aβ17–20 Peptide-Guided Structuring of Polymeric Conjugates and Their pH-Triggered Dynamic Response

      Sonu Kumar, Varun Bheemireddy and Priyadarsi De

      Article first published online: 17 JUN 2015 | DOI: 10.1002/mabi.201500134

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      “Smart” biohybrid polymers based on amyloidogenic short peptide segment Aβ17-20 are synthesized via RAFT method. The formation of unique nanostructures and α-helix-based secondary structures are obtained governed by peptide moieties. Post-polymerization modification approach is used to prepare PEGylated amphiphilic graft copolymer having imine linkage, which self-assemble into nanoparticles offering pH-triggered drug-release behavior.

    6. Polymer-Coated Magnetic Nanoparticles for Curcumin Delivery to Cancer Cells

      Serena Mancarella, Valentina Greco, Francesca Baldassarre, Daniele Vergara, Michele Maffia and Stefano Leporatti

      Article first published online: 17 JUN 2015 | DOI: 10.1002/mabi.201500142

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      A novel curcumin delivery system based on biodegradable polyelectrolyte-coated iron oxide magnetic nanoparticles is developed. These composite nano-Fe3O4 particles have a suitable size distribution, drug encapsulation efficiency, and drug release kinetics. Curcumin is successfully loaded inside nano-Fe3O4. Cytotoxicity assays show cell viability reduction upon curcumin release demonstrating high efficiency of this novel nanoformulation.

    7. Co-Culture of Human Endothelial Cells and Foreskin Fibroblasts on 3D Silk–Fibrin Scaffolds Supports Vascularization

      Juhi Samal, Stefan Weinandy, Agnieszka Weinandy, Marius Helmedag, Lisanne Rongen, Benita Hermanns-Sachweh, Subhas C. Kundu and Stefan Jockenhoevel

      Article first published online: 12 JUN 2015 | DOI: 10.1002/mabi.201500054

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      Current study hypothesizes that fabricated silk fibroin–fibrin combinatorial scaffolds can support the co-culture of HUVECs and human foreskin fibroblasts to yield an interconnected network of capillary-like structures. Silk fibroin provides the suitable mechanical strength and guides the formation of capillary-like structures in fibrin gel. To our knowledge, it is for the first time that a silk fibroin–fibrin combinatorial scaffold has been developed and used as a matrix to support vascularization.

  10. Communications

    1. PEGylation to Improve Protein Stability During Melt Processing

      Parker Lee, Jenna Towslee, João Maia and Jonathan Pokorski

      Article first published online: 12 JUN 2015 | DOI: 10.1002/mabi.201500143

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      PEG conjugated proteins were melt processed in polymer blends. Protein:PLGA blends were processed at high temperatures using a laboratory-built syringe extruder. The simple covalent conjugation of polyethylene glycol, as is often seen in biopharmaceuticals, provides enhanced dispersion and protein stability in the melt state and post-processing.

  11. Full Papers

    1. Promoting Cell Survival and Proliferation in Degradable Poly(vinyl alcohol)–Tyramine Hydrogels

      Khoon S. Lim, Yogambha Ramaswamy, Justine J. Roberts, Marie-Helene Alves, Laura A. Poole-Warren and Penny J. Martens

      Article first published online: 11 JUN 2015 | DOI: 10.1002/mabi.201500121

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      Antioxidative proteins (sericin and gelatin) are incorporated into PVA–Tyr gels to promote cell survival and proliferation following the photoencapsulation process. Addition of sericin alone is enough to protect cells from the radicals generated during the photocross-linking process, but both sericin and gelatin are needed synergistically to facilitate long-term 3D cell growth and proliferation.

    2. pH-Responsive H-Type PMAA2-b-HTPBN-b-PMAA2 Four-Arm Star Block Copolymer Micelles for PTX Drug Release

      Yan-Ling Luo, Mei Han, Feng Xu, Ya-Shao Chen and Yong-Qin Zhang

      Article first published online: 11 JUN 2015 | DOI: 10.1002/mabi.201500103

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      We are synthesizing H-type PMAA2-b-HTPBN-b-PMAA2 block copolymers. The copolymers could self-assemble into nanoscale spherical core-shell micelle aggregates. The micellization behavior and physicochemical properties are pH-dependent, and the pH phase transition located at 5.7–6.1. The micelle drug formulations exhibited pH-triggered release and cytotoxicity. The H-type block copolymer micelles are promising as drug targeting release carriers.

    3. Soft PEG-Hydrogels with Independently Tunable Stiffness and RGDS-Content for Cell Adhesion Studies

      Anika M. Jonker, Saskia A. Bode, Addie H. Kusters, Jan C. M. van Hest and Dennis W. P. M. Löwik

      Article first published online: 11 JUN 2015 | DOI: 10.1002/mabi.201500110

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      Soft poly(ethylene) glycol (PEG) hydrogels cross-linked via strain-promoted azide-alkyne cycloaddition (SPAAC) are prepared with independently tunable stiffness and RGDS-content. Rheology studies confirms the soft nature of the hydrogels. HOS cells adhere to all RGDS-containing gels independent of gel stiffness. HeLa cells and NIH 3T3 fibroblasts show significantly decreased cell adhesion on the stiffest hydrogel.

    4. Cellular Uptake Behavior of Doxorubicin-Conjugated Nanodiamond Clusters for Efficient Cancer Therapy

      Tae-Kyung Ryu, Gyoung-Ja Lee, Chang-Kyu Rhee and Sung-Wook Choi

      Article first published online: 11 JUN 2015 | DOI: 10.1002/mabi.201500176

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      We prepare doxorubicin (Dox)-conjugated nanodiamonds (ND) clusters with different sizes and systematically demonstrate high cellular uptake and ablation efficiency of Dox-ND clusters for cancer therapy.

    5. Design, Degradation Mechanism and Long-Term Cytotoxicity of Poly(l-lactide) and Poly(Lactide-co-ϵ-Caprolactone) Terpolymer Film and Air-Spun Nanofiber Scaffold

      Gad Sabbatier, Aitor Larrañaga, Andrée-Anne Guay-Bégin, Jorge Fernandez, Florence Diéval, Bernard Durand, Jose-Ramon Sarasua and Gaétan Laroche

      Article first published online: 8 JUN 2015 | DOI: 10.1002/mabi.201500130

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      Innovative degradable terpolymer nanofiber scaffold with finely tuned features lead to a better long-term interaction with specific cells than usual degradable biomaterial. This family of polymer can be used for degradable medical devices and has been applied as vascular biomaterial. Moreover, this article brings substantial new information in general aspects of biodegradable scaffold.

  12. Communications

    1. Synergistic Effects of SDF-1α and BMP-2 Delivery from Proteolytically Degradable Hyaluronic Acid Hydrogels for Bone Repair

      Julianne L. Holloway, Henry Ma, Reena Rai, Kurt D. Hankenson and Jason A. Burdick

      Article first published online: 8 JUN 2015 | DOI: 10.1002/mabi.201500178

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      The effect of dual delivery of SDF-1α and BMP-2 on in vivo bone repair is investigated, where biomolecule delivery is mediated via proteolytic hydrogel degradation. The delivery of SDF-1α in combination with BMP-2 results in improved in vivo osteogenesis and cell invasion and the effective BMP-2 dose for new bone repair is significantly reduced.

  13. Full Papers

    1. Shell Cross-Linked Polymeric Micelles as Camptothecin Nanocarriers for Anti-HCV Therapy

      Isabel Jiménez-Pardo, Rebeca González-Pastor, Alexandre Lancelot, Rafael Claveria-Gimeno, Adrián Velázquez-Campoy, Olga Abian, M. Blanca Ros and Teresa Sierra

      Article first published online: 5 JUN 2015 | DOI: 10.1002/mabi.201500094

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      Shell photocross-linked polymeric micelles transport efficiently camptothecin into hepatitis C infected cells and show lower toxicity than the free drug. A design based on a hybrid dendritic–linear–dendritic block copolymer yields a macromer that permit effective preparation of stable carriers. An amphiphilic fluorescent probe proves the internalization of the carriers within the cells.

    2. Biodegradable Nanotopography Combined with Neurotrophic Signals Enhances Contact Guidance and Neuronal Differentiation of Human Neural Stem Cells

      Kisuk Yang, Esther Park, Jong Seung Lee, Il-Sun Kim, Kwonho Hong, Kook In Park, Seung-Woo Cho and Hee Seok Yang

      Article first published online: 2 JUN 2015 | DOI: 10.1002/mabi.201500080

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      Biodegradable PLGA-patterned substrates with immobilization of ECM proteins via a DOPA coating significantly promote contact guidance and neuronal differentiation of hNSCs. The addition of neurotrophic factor (NGF) further enhances neurogenesis of hNSCs, indicating a synergistic effect of biophysical and biochemical cues on hNSC differentiation.

  14. Communications

    1. Curcumin Targeted, Polymalic Acid-Based MRI Contrast Agent for the Detection of Aβ Plaques in Alzheimer's Disease

      Rameshwar Patil, Pallavi R. Gangalum, Shawn Wagner, Jose Portilla-Arias, Hui Ding, Arthur Rekechenetskiy, Bindu Konda, Satoshi Inoue, Keith L. Black, Julia Y. Ljubimova and Eggehard Holler

      Article first published online: 2 JUN 2015 | DOI: 10.1002/mabi.201500062

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      Currently, there is no gadolinium-based contrast agent available for conventional magnetic resonance imaging (MRI) detection of amyloidal beta plaques in Alzheimer disease. We have designed a novel nanoimaging agent based on poly(β-l-malic acid) containing covalently attached curcumin and gadolinium–DOTA. This nanoimaging agent recognizes and selectively binds to Aβ plaques and is detectable by fluorescence and MRI.

  15. Full Papers

    1. Protein-Resistant Biodegradable Amphiphilic Graft Copolymer Vesicles as Protein Carriers

      Yupeng Wang, Lesan Yan, Bin Li, Yanxin Qi, Zhigang Xie, Xiabin Jing, Xuesi Chen and Yubin Huang

      Article first published online: 2 JUN 2015 | DOI: 10.1002/mabi.201500096

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      With enhanced resistance to protein adsorption, amphiphilic graft copolymers can self-assemble into vesicles in aqueous solutions, and entrap biomacromolecules (like hemoglobin) in the internal cavity. Meanwhile, they show lower permeability for water-soluble molecules compared with their block copolymer counterparts, providing a favorable platform as a hemoglobin delivery system for blood transfusion therapy.

    2. Dual Stimuli-Responsive Poly(β-amino ester) Nanoparticles for On-Demand Burst Release

      Jung Seok Lee, Xiaojian Deng, Patrick Han and Jianjun Cheng

      Article first published online: 2 JUN 2015 | DOI: 10.1002/mabi.201500111

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      Disassembly of poly(β-amino esters) nanoparticles is triggered by UV irradiation or change of solution pH for controlled burst release of payloads. The turbid suspension of the nanoparticles becomes clear upon induction of UV or pH stimuli, indicating particle dissolution into water.

  16. Communications

    1. Instructive Conductive 3D Silk Foam-Based Bone Tissue Scaffolds Enable Electrical Stimulation of Stem Cells for Enhanced Osteogenic Differentiation

      John G. Hardy, Sydney A. Geissler, David Aguilar Jr., Maria K. Villancio-Wolter, David J. Mouser, Rushi C. Sukhavasi, R. Chase Cornelison, Lee W. Tien, R. Carmen Preda, Rebecca S. Hayden, Jacqueline K. Chow, Lindsey Nguy, David L. Kaplan and Christine E. Schmidt

      Article first published online: 1 JUN 2015 | DOI: 10.1002/mabi.201500171

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      Instructive tissue scaffolds capable of controlling the behavior of the cells that reside within them are particularly interesting for tissue engineering. Herein we describe the preparation of conductive silk foam-based bone tissue scaffolds that enable the electrical stimulation of human mesenchymal stem cells to enhance their differentiation toward osteogenic outcomes.

    2. Substantial Differentiation of Human Neural Stem Cells Into Motor Neurons on a Biomimetic Polyurea

      Donghwa Yun, Young M. Lee, Melissa R. Laughter, Curt R. Freed and Daewon Park

      Article first published online: 29 MAY 2015 | DOI: 10.1002/mabi.201500066

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      Human neural stem cells are successfully cultured and differentiated into motor neurons on a biomimetic polymer functionalized with RGD. Mature motor neurons are able to survive and proliferate efficiently on this synthetic coating demonstrating its potential to act as an implantable cell scaffold for spinal cord injury treatment.

  17. Full Papers

    1. Dendritic Glycopolymer as Drug Delivery System for Proteasome Inhibitor Bortezomib in a Calcium Phosphate Bone Cement: First Steps Toward a Local Therapy of Osteolytic Bone Lesions

      Christin Striegler, Matthias Schumacher, Christiane Effenberg, Martin Müller, Anja Seckinger, Reinhard Schnettler, Brigitte Voit, Dirk Hose, Michael Gelinsky and Dietmar Appelhans

      Article first published online: 28 MAY 2015 | DOI: 10.1002/mabi.201500085

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      Maltose-containing drug delivery systems (DDS) for complexation of the boronic acid containing proteasome inhibitor bortezomib are suitable for application in calcium phosphate bone cements. Release of bortezomib from specific DDS/bone cement composites is retarded in comparison to that of cements, loaded directly with the drug.

    2. The Relationship Between Water Structure and Blood Compatibility in Poly(2-methoxyethyl Acrylate) (PMEA) Analogues

      Kazuhiro Sato, Shingo Kobayashi, Miho Kusakari, Shogo Watahiki, Masahiko Oikawa, Takashi Hoshiba and Masaru Tanaka

      Article first published online: 28 MAY 2015 | DOI: 10.1002/mabi.201500078

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      The antithrombogenic property of PMEA analogues is studied, paying special attention to the hydration water structure of the polymers. The amount of adsorbed bovine serum albumin and the exposure degree of platelet adhesion sites for fibrinogen shows a decreasing trend with increasing the amount of freezing-bound water (intermediate water), and thus platelet adhesion is suppressed on PMEA analogues.

    3. Attachment of Poly(l-lactide) Nanoparticles to Plasma-Treated Non-Woven Polymer Fabrics Using Inkjet Printing

      Tatiana V. Ivanova, Grit Baier, Katharina Landfester, Eduard Musin, Sameer A. Al-Bataineh, David C. Cameron, Tomáš Homola, Jason D. Whittle and Mika Sillanpää

      Article first published online: 27 MAY 2015 | DOI: 10.1002/mabi.201500067

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      The integrated engineering solution is developed for the production of active wound dressings with poly(l-lactide) (PLLA) nanoparticles containing the antimicrobial agent octenidine and perylene dye on non-woven polymers. The process involves a surface pretreatment of the non-woven fabric using plasma jet and the immobilization of nanoparticles on non-woven polymer surfaces by using an inkjet printing process.

  18. Communications

    1. Tumor-Targeting Co-Delivery of Drug and Gene from Temperature-Triggered Micelles

      Seog-Jin Seo, Seon-Young Lee, Seong-Jun Choi and Hae-Won Kim

      Article first published online: 19 MAY 2015 | DOI: 10.1002/mabi.201500137

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      Our multifunctional nanocarrier system designed for tumor-targeting co-delivery shows controlled release behaviors of hydrophobic molecules at tumors by a temperature trigger and receptor-mediated gene delivery. The unique property of this system is demonstrated by a series of logical characterization measurements, which suggests that this system has a potential for the hyperthermia treatment.

  19. Full Papers

    1. Trivalent Cation Induced Bundle Formation of Filamentous fd Phages

      Nuriye Korkmaz Zirpel and Eun Jin Park

      Article first published online: 18 MAY 2015 | DOI: 10.1002/mabi.201500046

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      Aggregated bacteriophage bundles are obtained upon treatment of filamentous fd phages with trivalent counterions of varying ionic radii. Condensation of phages results in formation of either networking layer-like structures or denser intertwined agglomerated phage constructs. Self-assembly of molecular sub-units into functional assemblies in vivo and in vitro can be understood by studying polyelectrolyte properties of biomolecules like phages.

  20. Review

    1. You have free access to this content
      Polyphosphate: A Morphogenetically Active Implant Material Serving as Metabolic Fuel for Bone Regeneration

      Werner E. G. Müller, Emad Tolba, Heinz C. Schröder and Xiaohong Wang

      Article first published online: 15 MAY 2015 | DOI: 10.1002/mabi.201500100

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      Polyphosphate (polyP) is a natural inorganic polymer that is synthesized in cells in close vicinity of bone tissue. This polymer is biocompatible and bioresorbable. The characteristic features of polyP are the physiological origin and the huge conserved reservoir of metabolic energy. Since Ca-polyP is built of phosphate and Ca2+, it can be fabricated to bone scaffolds.

  21. Full Papers

    1. Synergistically Improved Anti-tumor Efficacy by Co-delivery Doxorubicin and Curcumin Polymeric Micelles

      Jinling Wang, Wenzhuan Ma and Pengfei Tu

      Article first published online: 15 MAY 2015 | DOI: 10.1002/mabi.201500043

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      Co-encapsulated DOX and Cur micelles are designed to simultaneously deliver chemotherapeutic drug and multi-drug resistance (MDR) modulator to tumor sites. Co-delivery micelles exhibited excellent cytotoxicity, cellular uptake and cellular apoptosis in MCF7/Adr cells, and effective tumor inhibitory effects in 4T1-bearing mice. Therefore, co-encapsulated DOX and Cur micelles could be a promising vehicle for overcoming MDR and improving antitumor efficacy.

    2. Nanoparticle Formulation of AEA and BAEA Cellulose Carbamates Increases Biocompatibility and Antimicrobial Activity

      Cornelia Wiegand, Melanie Nikolajski, Uta-Christina Hipler and Thomas Heinze

      Article first published online: 15 MAY 2015 | DOI: 10.1002/mabi.201500031

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      Antimicrobially active polymers gain increasing interest in health care. AEA and BAEA cellulose carbamates exhibit a significant antimicrobial activity with moderate cell compatibility. Biocompatibility is enhanced by nanoparticle formulation. AEA cellulose carbamate NPs demonstrate a ratio of LC50/IC50 that is four to six times higher than that of BAEA cellulose carbamate NPs.

    3. Hyaluronic Acid/Poly-l-Lysine Multilayers as Reservoirs for Storage and Release of Small Charged Molecules

      Vladimir Z. Prokopović, Claus Duschl and Dmitry Volodkin

      Article first published online: 15 MAY 2015 | DOI: 10.1002/mabi.201500093

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      Polyelectrolyte multilayer films composed of biocompatible polymers hyaluronic acid and poly-l-lysine are assembled and their ability to store and release small charged molecules is studied. The films show high storage capacity and sustain release profiles, and these phenomena are explained by the proposed mechanism based on charge balance and polymer dynamics in the film.

    4. Poly-l-Lysine–Poly[HPMA] Block Copolymers Obtained by RAFT Polymerization as Polyplex-Transfection Reagents with Minimal Toxicity

      Kristof Tappertzhofen, Franziska Weiser, Evelyn Montermann, Angelika Reske-Kunz, Matthias Bros and Rudolf Zentel

      Article first published online: 13 MAY 2015 | DOI: 10.1002/mabi.201500022

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      Polyplexes from cationic poly-l-lysine–b–poly[N-(2-hydroxypropyl) methacrylamide] (p[HPMA]) block copolymers and p-DNA mediate efficient cellular uptake and facilitate transfection, while showing minimal toxicity. Hence, they may present suitable polymeric transfection vectors for sensitive immune cells.

    5. Selective Cell Adhesion and Biosensing Applications of Bio-Active Block Copolymers Prepared by CuAAC/Thiol-ene Double Click Reactions

      Gizem Oyman Eyrilmez, Sean Doran, Eljesa Murtezi, Bilal Demir, Dilek Odaci Demirkol, Hakan Coskunol, Suna Timur and Yusuf Yagci

      Article first published online: 13 MAY 2015 | DOI: 10.1002/mabi.201500099

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      N-Acetyl-l-cysteine (NAC)-capped poly(methyl methacrylate)-b-polycaprolactone block copolymer (PMMA-b-PCL-NAC) is synthesized using one-pot photoinduced sequential CuAAC/thiol-ene double click procedure. The constructed surfaces within the modification of RGD peptide are used for the selective cell binding in the way of cell viability and electrochemical biosensing platform. Glioblastoma cells are found to be more selective to PMMA-b-PCL-NAC/RGD surface than HaCaT keratinocytes.

  22. Communications

    1. POxylated Polyurea Dendrimers: Smart Core-Shell Vectors with IC50 Lowering Capacity

      Rita B. Restani, João Conde, Rita F. Pires, Pedro Martins, Alexandra R. Fernandes, Pedro V. Baptista, Vasco D. B. Bonifácio and Ana Aguiar-Ricardo

      Article first published online: 12 MAY 2015 | DOI: 10.1002/mabi.201500131

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      Core-shell nanocarriers obtained by POxylation of polyurea dendrimers in supercritical CO2 are able to reduce 100-fold the IC50 dose of encapsulated placlitaxel. These water-soluble smart vectors are intrinsically fluorescent, pH responsive, and show lower toxicity when compared to pristine PURE-type dendrimers. POxylation using oligo-oxazolines is presented as a novel tool for next generation low cost and highly efficient nanotherapeutics.

  23. Full Papers

    1. Dual-Responsive pH and Temperature Sensitive Nanoparticles Based on Methacrylic Acid and Di(ethylene glycol) Methyl Ether Methacrylate for the Triggered Release of Drugs

      Yee Yee Khine, Yanyan Jiang, Aydan Dag, Hongxu Lu and Martina H. Stenzel

      Article first published online: 7 MAY 2015 | DOI: 10.1002/mabi.201500057

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      Modulation of the cloud point of PDEGMA by copolymerization with methacrylic acid resulted in the formation of a micelle shell that is not only responsive to temperature changes, but also the pH changes. The release of the drug was significantly accelerated above the cloud point causing the triggered release of the in a slightly acidic environment.

    2. Biodegradable Microcarriers of Poly(Lactide-co-Glycolide) and Nano-Hydroxyapatite Decorated with IGF-1 via Polydopamine Coating for Enhancing Cell Proliferation and Osteogenic Differentiation

      Tianlin Gao, Ning Zhang, Zongliang Wang, Yu Wang, Ya Liu, Yoshihiro Ito and Peibiao Zhang

      Article first published online: 7 MAY 2015 | DOI: 10.1002/mabi.201500069

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      The poly(lactide-co-glycolide) and nano-hydroxyapatite (PLGA/HA) microcarriers are fabricated by O/W emulsion, and IGF-1 is effectively immobilized on the microcarriers by polydopamine coating. After the immobilization of IGF-1, the PLGA/HA microcarriers exhibit excellent bioactivities for supporting the adhesion, proliferation, and osteogenic differentiation of ADSCs, which is promising in the bone tissue engineering.

    3. Injectable Hyaluronan Hydrogels with Peptide-Binding Dendrimers Modulate the Controlled Release of BMP-2 and TGF-β1

      Ryan J. Seelbach, Peter Fransen, Daniel Pulido, Matteo D'Este, Fabian Duttenhoefer, Sebastian Sauerbier, Thomas M. Freiman, Philipp Niemeyer, Fernando Albericio, Mauro Alini, Miriam Royo, Alvaro Mata and David Eglin

      Article first published online: 5 MAY 2015 | DOI: 10.1002/mabi.201500082

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      The molecular architecture of an injectable hydrogel carrier is modulated with dendrimers designed to selectively bind proteins. Hence, growth factor-loaded biomaterials augmented with these affinity binding nanostructures can attenuate the local delivery of drugs that promote bone regeneration.

    4. Cationic Polyrotaxanes as a Feasible Framework for the Intracellular Delivery and Sustainable Activity of Anionic Enzymes: A Comparison Study with Methacrylate-Based Polycations

      Atsushi Tamura, Go Ikeda, Kei Nishida and Nobuhiko Yui

      Article first published online: 29 APR 2015 | DOI: 10.1002/mabi.201500083

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      To ascertain the effect of supramolecular backbone structure of cationic polyrotaxanes in the intracellular delivery of anionic enzymes, the physichochemical properties and the intracellular delivery efficacy of the complexes were investigated in comparison to a linear polycation.

    5. Silver Nanoparticle Coated Bioactive Glasses – Composites with Dex/CMC Hydrogels: Characterization, Solubility, and In Vitro Biological Studies

      Anthony W. Wren, Pegah Hassanzadeh, Lana M. Placek, Timothy J. Keenan, Aisling Coughlan, Lydia R. Boutelle and Mark R. Towler

      Article first published online: 29 APR 2015 | DOI: 10.1002/mabi.201500109

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      This study sees the synthesis of AgNP coated bioactive glass particles which were incorporated into Dex/CMC hydrogels for localized therapeutic effects. Solubility profiles were determined in addition to evaluating toxicity levels in eukaryotic cells. Additionally, antibacterial properties were evaluated in microbes such as S. aureus, E. coli, and S. epidermidis.

    6. Evaluation of Surface Microtopography Engineered by Direct Laser Interference for Bacterial Anti-Biofouling

      Jaione Valle, Saioa Burgui, Denise Langheinrich, Carmen Gil, Cristina Solano, Alejandro Toledo-Arana, Ralf Helbig, Andrés Lasagni and Iñigo Lasa

      Article first published online: 27 APR 2015 | DOI: 10.1002/mabi.201500107

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      Three-dimensional micrometer periodic structures generated by direct laser interference patterning (DLIP) on polystyrene surfaces have a profound effect on S. aureus adhesion. Pillar-like topographical patterns enhanced S. aureus adhesion, whereas complex lamella microtopography reduced S. aureus adhesion both in static and continuous flow culture conditions and in a model of biofilm formation in vivo.

    7. Structural Mimetic Silk Fiber-Reinforced Composite Scaffolds Using Multi-Angle Fibers

      Gang Li, Jian Liu, Zhaozhu Zheng, Xiaoqin Wang and David L. Kaplan

      Article first published online: 16 APR 2015 | DOI: 10.1002/mabi.201400502

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      In order to develop a successful tissue engineered scaffold for the treatment of meniscus loss, this work starts with understanding and mimicking its complex internal architecture and function, and then develops a structural mimetic scaffolds reinforced with multi-angle silk fibers. The fiber reinforcement technique and mechanisms elucidated in this study can also be expanded to other mechanical strength-demanding tissue regeneration needs.

    8. Enzymatic Polymerization of an Ibuprofen-Containing Monomer and Subsequent Drug Release

      Nicholas D. Stebbins, Weiling Yu and Kathryn E. Uhrich

      Article first published online: 16 APR 2015 | DOI: 10.1002/mabi.201500030

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      Through enzymatic methods, drug-containing monomers were polymerized to afford linear polyesters with pendant bioactive groups. Nuclear magnetic resonance and Fourier transform infrared spectroscopies determined precursor and polymer structures. The polymers exhibited sustained hydrolytic release of ibuprofen, along with other natural and biocompatible compounds over the 30 d study. Released ibuprofen retained its chemical structure following synthesis and hydrolytic degradation.

    9. Living Composites of Bacteria and Polymers as Biomimetic Films for Metal Sequestration and Bioremediation

      Christian Knierim, Michaela Enzeroth, Patrick Kaiser, Christian Dams, David Nette, Andreas Seubert, Andreas Klingl, Charles L. Greenblatt, Valérie Jérôme, Seema Agarwal, Ruth Freitag and Andreas Greiner

      Article first published online: 7 APR 2015 | DOI: 10.1002/mabi.201400538

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      Water-insoluble core-shell fibers of PVA and PPX containing M. luteus or N. winogradskyi were achieved by utilizing wet spinning in combination with CVD. The leaking of bacteria from the fibers is retarded in aqueous solution. The immobilized bacteria were used for sequestration of gold and degradation of nitrite from aqueous solutions. The biosorption of gold lead to encapsulated gold nanoparticles as analyzed by EDX, ICP-MS, and TEM.

    10. Fabrication and Characterization of Gd-DTPA-Loaded Chitosan–Poly(Acrylic Acid) Nanoparticles for Magnetic Resonance Imaging

      Arsalan Ahmed, Chao Zhang, Jian Guo, Yong Hu and Xiqun Jiang

      Article first published online: 7 APR 2015 | DOI: 10.1002/mabi.201500034

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      Gd-DTPA-loaded chitosan–poly(acrylic acid) NPs were fabricated. These obtained NPs have a spherical shape with a size about 220 nm. They were stable in normal aqueous solution with positive surface charges and showed pH sensitivity in in vitro release and relaxation experiments. In vivo biodistribution and MRI studies have also demonstrated selective localization of contrast agent and enhanced contrast, respectively.

    11. Vitamin Bc-Bearing Hydrophilic Photosensitizer Conjugate for Photodynamic Cancer Theranostics

      Jiyoung Kim, Kyoung Sub Kim, Sin-jung Park and Kun Na

      Article first published online: 31 MAR 2015 | DOI: 10.1002/mabi.201500060

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      Vitamin Bc-bearing hydrophilic photosensitizer conjugate, folic acid-polyethylene glycol-pheophorbideA (FA-PEG-PheoA), was synthesized for photodynamic cancer theranostics. By conjugating FA with a photosensitizer that can be used in optical imaging and further clinical treatment, FA-PEG-PheoA was delivered to the FA receptor overexpressing cancer and utilized for cancer diagnosis and therapy simultaneously.


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