Advanced Healthcare Materials

Cover image for Vol. 3 Issue 6

June, 2014

Volume 3, Issue 6

Pages 789–945

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      Drug Delivery: Ultrasound-Triggered Regulation of Blood Glucose Levels Using Injectable Nano-Network (Adv. Healthcare Mater. 6/2014) (page 789)

      Jin Di, Jennifer Price, Xiao Gu, Xiaoning Jiang, Yun Jing and Zhen Gu

      Version of Record online: 10 JUN 2014 | DOI: 10.1002/adhm.201470027

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      On page 811, Y. Jing, Z. Gu and co-workers present the integration of an injectable nano-network with a focused ultrasound system (FUS) which can remotely regulate insulin release both in vitro and in vivo. Serving as a synthetic insulin reservoir, the nano-network consisting of adhesive biodegradable nanoparticles promotes insulin release upon FUS triggers in a pulsatile, remote and non-invasive control manner. Image courtesy of Dwayne Martin.

  2. Inside Front Cover

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      Bone Repair: Osteotropic Therapy via Targeted Layer-by-Layer Nanoparticles (Adv. Healthcare Mater. 6/2014) (page 790)

      Stephen W. Morton, Nisarg J. Shah, Mohiuddin A. Quadir, Zhou J. Deng, Zhiyong Poon and Paula T. Hammond

      Version of Record online: 10 JUN 2014 | DOI: 10.1002/adhm.201470028

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      Nanomedicine that can target bone tissue for disease treatment is designed by P. Hammond and team on page 867 by modifying the surface of therapeutic-containing particles with nanolayers of a polymer decorated with moieties that specifically bind boney regions. In this way, drug therapies can be directed to diseased bone tissue for improved treatment outcomes. LbL on nanoparticles is a versatile platform for tuning tissue specificity and therapeutic efficacy, in a controlled manner, one layer at a time.

  3. Back Cover

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      Diagnostic Devices: Microneedle-Based Transdermal Sensor for On-Chip Potentiometric Determination of K+ (Adv. Healthcare Mater. 6/2014) (page 948)

      Philip R. Miller, Xiaoyin Xiao, Igal Brener, D. Bruce Burckel, Roger Narayan and Ronen Polsky

      Version of Record online: 10 JUN 2014 | DOI: 10.1002/adhm.201470032

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      A transdermal sensing platform for detection of electrolytes is developed by P. R. Miller, R. Narayan, R. Polsky and colleagues. On page 876, hollow polymer microneedles are integrated with a microfluidic chip for detecting potassium using a solid state ion selective electrode transducer. The device could one day be used as an on body point-of-care medical diagnostic device.

  4. Masthead

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      Masthead: (Adv. Healthcare Mater. 6/2014)

      Version of Record online: 10 JUN 2014 | DOI: 10.1002/adhm.201470031

  5. Contents

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  6. Reviews

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    1. Engineering Biomolecular Microenvironments for Cell Instructive Biomaterials (pages 797–810)

      Catarina A. Custódio, Rui L. Reis and João F. Mano

      Version of Record online: 27 JAN 2014 | DOI: 10.1002/adhm.201300603

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      This Review is focused on the assortment of biochemical signals that have been explored to fabricate bioactive cell microenvironments. The main receptor molecules that the cell has available on its surface that interacts with external ligands are also considered. Existing tools to pattern and functionalize cell microenvironments with active biologic motifs are described in the last part.

  7. Communications

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    1. Ultrasound-Triggered Regulation of Blood Glucose Levels Using Injectable Nano-Network (pages 811–816)

      Jin Di, Jennifer Price, Xiao Gu, Xiaoning Jiang, Yun Jing and Zhen Gu

      Version of Record online: 19 NOV 2013 | DOI: 10.1002/adhm.201300490

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      The integration of an injectable insulin-encapsulated nano-network with a focused ultrasound system (FUS) can remotely regulate insulin release both in vitro and in vivo. A single subcutaneous injection of the nano-network with intermittent FUS administration facilitates reduction of the blood glucose levels in type 1 diabetic mice for up to 10 d.

    2. Poly(3-hydroxybutyrate-co-R-3-hydroxyhexanoate) Nanoparticles with Polyethylenimine Coat as Simple, Safe, and Versatile Vehicles for Cell Targeting: Population Characteristics, Cell Uptake, and Intracellular Trafficking (pages 817–824)

      Lin-Ping Wu, Danyang Wang, Ladan Parhamifar, Arnaldur Hall, Guo-Qiang Chen and Seyed M. Moghimi

      Version of Record online: 10 JAN 2014 | DOI: 10.1002/adhm.201300533

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      A simple and highly safe poly(3-hydroxybutyrate-co-R-3-hydroxyhexanoate) nanoparticulate delivery system that targets different cell types is developed. A sub-cytotoxic level of polyethylenimine coat mediates universal cell targeting. Internalized nanoparticles traffic along endolysosomal compartments, endoplasmic reticulum and the Golgi complex. Nanoparticles have no detrimental effects on cell morphology and respiration.

    3. Sono-Assembly of Highly Biocompatible Polysaccharide Capsules for Hydrophobic Drug Delivery (pages 825–831)

      Hongqiang Wang, Xuehai Yan, Guo Liang Li, Christine Pilz-Allen, Helmuth Möhwald and Dmitry Shchukin

      Version of Record online: 9 DEC 2013 | DOI: 10.1002/adhm.201300596

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      Cells like sugar. General synthesis and potential of intracellular hydrophobic drug delivery of single-component polysaccharide capsules are pursued. The capsules can be generally assembled through hydrogen bonding networks but show striking shell robustness. The evidenced cell internalization, stimuli-responsiveness to local pH changes and high biocompatibilities of the capsules specifically favor their potential intracellular drug delivery

    4. New Insights Into Alzheimer's Disease Amyloid Inhibition: Nanosized Metallo-Supramolecular Complexes Suppress Aβ-Induced Biosynthesis of Heme and Iron Uptake in PC12 Cells (pages 832–836)

      Meng Li, Chuanqi Zhao, Taicheng Duan, Jinsong Ren and Xiaogang Qu

      Version of Record online: 29 OCT 2013 | DOI: 10.1002/adhm.201300470

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      Nanosized metallo-supramolecular compounds, [Ni2L3]4+ and [Fe2L3]4+, can not only strongly inhibit Aβ aggregation but also reduce the peroxidase activity of Aβ–heme. Further studies demonstrate that through blocking the heme-binding site, these two compounds can suppress Aβ-induced biosynthesis of heme and iron uptake in PC12 cells. This work provides new insights into molecular mechanisms of Aβ inhibitors on Aβ-mediated neurotoxicity.

    5. Whole Blood Cells Loaded with Messenger RNA as an Anti-Tumor Vaccine (pages 837–842)

      Kyle K. L. Phua, David Boczkowski, Jens Dannull, Scott Pruitt, Kam W. Leong and Smita K. Nair

      Version of Record online: 16 DEC 2013 | DOI: 10.1002/adhm.201300512

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      The use of a cell-based vaccine composed of autologous whole blood cells loaded with mRNA is described. Mice immunized with whole blood cells loaded with mRNA encoding antigen develop anti-tumor immunity comparable to DC-RNA immunization. This approach offers a simple and affordable alternative to RNA-based cellular therapy by circumventing complex, laborious and expensive ex vivo manipulations required for DC-based immunizations.

    6. Facile Fabrication of Polyanhydride/Anesthetic Nanoparticles with Tunable Release Kinetics (pages 843–847)

      Bret D. Ulery, Ho-Man Kan, Bryce A. Williams, Balaji Narasimhan, Kevin W.-H. Lo, Lakshmi S. Nair and Cato T. Laurencin

      Version of Record online: 27 DEC 2013 | DOI: 10.1002/adhm.201300521

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      This work illustrates a two-step strategy for the fabrication of polymer/drug nanoparticles. Utilizing solvent/non-solvent precipitation and gaseous basification, composite nanoparticles with 0–100% drug loadings are fabricated. Drug release kinetics are dictated by nanoparticle composition allowing future tuning for therapeutic applications.

    7. High-Density Polymer Microarrays: Identifying Synthetic Polymers that Control Human Embryonic Stem Cell Growth (pages 848–853)

      Anne Hansen, Heidi K. Mjoseng, Rong Zhang, Michail Kalloudis, Vasileios Koutsos, Paul A. de Sousa and Mark Bradley

      Version of Record online: 18 DEC 2013 | DOI: 10.1002/adhm.201300489

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      The fabrication of high-density polymer microarray is described, allowing the simultaneous and efficient evaluation of more than 7000 different polymers in a single-cellular-based screen. These high-density polymer arrays are applied in the search for synthetic substrates for hESCs culture. Up-scaling of the identified hit polymers enables long-term cellular cultivation and promoted successful stem-cell maintenance.

    8. Hyperthermia-Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy (pages 854–859)

      Adolfo López-Noriega, Conn L. Hastings, Burcin Ozbakir, Kathleen E. O'Donnell, Fergal J. O'Brien, Gert Storm, Wim E. Hennink, Garry P. Duffy and Eduardo Ruiz-Hernández

      Version of Record online: 16 JAN 2014 | DOI: 10.1002/adhm.201300649

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      A novel drug delivery system, enabling an in situ, thermally triggered drug release is described, consisting of an injectable thermoresponsive chitosan hydrogel containing doxorubicin-loaded thermosensitive liposomes. The design, fabrication, characterization, and an assessment of in vitro bioactivity of this formulation is detailed. Combining on-demand drug delivery with in situ gelation results in a promising candidate for local chemotherapy.

    9. High Aspect Ratio Elongated Microparticles for Enhanced Topical Drug Delivery in Human Volunteers (pages 860–866)

      Anthony P. Raphael, Clare A. Primiero, Lynlee L. Lin, Ross Flewell Smith, Philip Dyer, H. Peter Soyer and Tarl W. Prow

      Version of Record online: 13 JAN 2014 | DOI: 10.1002/adhm.201300517

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      Delivery of therapeutics into skin is hindered by the epidermal barriers. To overcome these barriers for the treatment of skin diseases, a cutaneous delivery method capable of field treatment using silica-elongated microparticles is developed. The microparticles are massaged into the skin using a 3D-printed microtextured applicator resulting in significant field-directed drug delivery enhancement.

  8. Full Papers

    1. Top of page
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    3. Inside Front Cover
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    5. Masthead
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    9. Full Papers
    10. Frontispiece
    11. Full Papers
    12. Research News
    1. Osteotropic Therapy via Targeted Layer-by-Layer Nanoparticles (pages 867–875)

      Stephen W. Morton, Nisarg J. Shah, Mohiuddin A. Quadir, Zhou J. Deng, Zhiyong Poon and Paula T. Hammond

      Version of Record online: 9 OCT 2013 | DOI: 10.1002/adhm.201300465

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      Bone-targeted nanoparticles are manufactured via Layer-by-Layer electrostatic adsorption of an alendronate-functionalized polyelectrolyte, poly(acrylic acid), on a nanoparticle substrate. High levels of bone specificity and efficacy against an osteosarcoma xenograft tumor model demonstrate this approach as an attractive, modular method for designing systems with tissue specificity for enhanced treatment outcomes.

    2. Microneedle-Based Transdermal Sensor for On-Chip Potentiometric Determination of K+ (pages 876–881)

      Philip R. Miller, Xiaoyin Xiao, Igal Brener, D. Bruce Burckel, Roger Narayan and Ronen Polsky

      Version of Record online: 21 DEC 2013 | DOI: 10.1002/adhm.201300541

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      A new integrated microneedle-based microfluidic platform is described for in vivo potassium sensing. Fluid can be extracted through a hollow microneedle and run over a downstream porous carbon solid state ion selective electrode to detect physiological levels of potassium.

    3. Enhancement of Cationic Antimicrobial Materials via Cholesterol Incorporation (pages 882–889)

      Daniel J. Coady, Zhan Yuin Ong, Pei Shan Lee, Shrinivas Venkataraman, Willy Chin, Amanda C. Engler, Yi Yan Yang and James L. Hedrick

      Version of Record online: 12 DEC 2013 | DOI: 10.1002/adhm.201300554

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      Cholesterol-functionalized cationic polycarbonates are investigated as a means of improving lipid bilayer assimilation and antimicrobial activity. The natural properties of cholesterol provide an ideal hydrophobic region by directing discotic self-assembly and engendering enhanced membrane integration

  9. Frontispiece

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      Hydrogels: Pd-Porphyrin-Cross-Linked Implantable Hydrogels with Oxygen-Responsive Phosphorescence (Adv. Healthcare Mater. 6/2014) (page 890)

      Haoyuan Huang, Wentao Song, Guanying Chen, Justin M. Reynard, Tymish Y. Ohulchanskyy, Paras N. Prasad, Frank V. Bright and Jonathan F. Lovell

      Version of Record online: 10 JUN 2014 | DOI: 10.1002/adhm.201470030

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      J. F. Lovell and team present a new strategy to create a biocompatible implantable hydrogel for non-invasive oxygen sensing. On page 891, a tetracarboxy porphyrin is reacted with PEG diamines under conditions that result in nearly quantitative dye incorporation. Polyamide is formed with millimolar porphyrins exhibiting near infrared phosphorescence, ideal for in vivo detection. The spatially constraining mesh of the PEG-porphyrin matrix prevents porphyrin aggregation that would normally occur at such dye concentrations and attenuate the phosphorescence. The hydrogel can be implanted in mice for weeks without signs of toxicity, signal loss or polymer degradation, and could non-invasively detect changes in subcutaneous oxygen levels via transdermal phosphorescence detection.

  10. Full Papers

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    1. Pd-Porphyrin-Cross-Linked Implantable Hydrogels with Oxygen-Responsive Phosphorescence (pages 891–896)

      Haoyuan Huang, Wentao Song, Guanying Chen, Justin M. Reynard, Tymish Y. Ohulchanskyy, Paras N. Prasad, Frank V. Bright and Jonathan F. Lovell

      Version of Record online: 20 NOV 2013 | DOI: 10.1002/adhm.201300483

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      Pd-porphyrins are used as cross-linkers to generate an oxygen-responsive polyamide hydrogel. The implantable hydrogel is stable in vivo for weeks, biocompatible, and the high density of the Pd-porphyrin enables transdermal detection. By changing Pd chelation for Cu and free base porphyrins, an intensity-matched companion hydrogel is developed for a ratiometric sensing strategy.

    2. Recombinant Human Lactoferrin as a Biomaterial for Bone Tissue Engineering: Mechanism of Antiapoptotic and Osteogenic Activity (pages 897–905)

      Ashley A. Amini and Lakshmi S. Nair

      Version of Record online: 18 DEC 2013 | DOI: 10.1002/adhm.201300496

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      The feasibility of developing an injectable hydrogel from a biologically active protein, “lactoferrin”, is investigated. The injectable lactoferrin gels support the viability, proliferation, and differentiation of encapsulated MC3T3 cells. The antiapoptotic properties of lactoferrin are found to be mediated by Wnt5a/PKA pathway and stabilization of beta-catenin by PKA/LRP6 pathway.

    3. Smart Nanorods for Highly Effective Cancer Theranostic Applications (pages 906–915)

      Yinlong Yang, Xiujuan Zhang, Caitong Yu, Xiaojun Hao, Jiansheng Jie, Mengjiao Zhou and Xiaohong Zhang

      Version of Record online: 27 DEC 2013 | DOI: 10.1002/adhm.201300463

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      A smart drug nanorods-based multifunctional nanocomposites with drug payload up to 72 wt% is devolped for highly effective chemo-photothermal combined cancer therapy as well as tumor imaging. 100% in vivo tumor elimination without tumor recurrence is achieved at a low laser power density of 1 W cm2 with low systematic toxicity.

    4. Reduction in Wound Bioburden using a Silver-Loaded Dissolvable Microfilm Construct (pages 916–928)

      Maggie Herron, Ankit Agarwal, Patricia R. Kierski, Diego F. Calderon, Leandro B. C. Teixeira, Michael J. Schurr, Christopher J. Murphy, Charles J. Czuprynski, Jonathan F. McAnulty and Nicholas L. Abbott

      Version of Record online: 12 FEB 2014 | DOI: 10.1002/adhm.201300537

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      Silver is a well-known antimicrobial agent, yet, when used in wounds, it can lead to staining, tissue toxicity, and impairment of healing. Laminated constructs composed of silver-loaded polymeric nanofilms and micrometer-thick dissolvable casts provide a facile ­approach for delivery of silver to wounds. Therapeutic effects are measured at loadings and release rates of silver two orders of magnitude lower than conventional silver-loaded dressings.

    5. Electrospun PGS:PCL Microfibers Align Human Valvular Interstitial Cells and Provide Tunable Scaffold Anisotropy (pages 929–939)

      Nafiseh Masoumi, Benjamin L. Larson, Nasim Annabi, Mahshid Kharaziha, Behnam Zamanian, Kayle S. Shapero, Alexander T. Cubberley, Gulden Camci-Unal, Keefe. B. Manning, John E. Mayer Jr. and Ali Khademhosseini

      Version of Record online: 22 JAN 2014 | DOI: 10.1002/adhm.201300505

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      A novel scaffold containing fiber structures is fabricated resembling the ECM networks in the native heart valve leaflet. Directional electrospinning is used to create tunable anisotropic composite materials with varying ratios of PGS:PCL. The human valvular interstitial cells (VICs) are found to be organized and aligned along the anisotropic axes of the composite TEHVs.

  11. Research News

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    1. Microfluidics Expands the Zebrafish Potentials in Pharmaceutically Relevant Screening (pages 940–945)

      Chia-Yuan Chen and Chao-Min Cheng

      Version of Record online: 24 JAN 2014 | DOI: 10.1002/adhm.201300546

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      A microfluidics-based zebrafish platform, which is capable of processing all demanded tests in parallel, could accelerate the entire drug inventing process significantly with less cost.

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