Advanced Healthcare Materials

Cover image for Vol. 3 Issue 4

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


  1. 1 - 100
  2. 101 - 117
  1. Communications

    1. You have full text access to this OnlineOpen article
      Confinement and Deformation of Single Cells and Their Nuclei Inside Size-Adapted Microtubes

      Britta Koch, Samuel Sanchez, Christine K. Schmidt, Anka Swiersy, Stephen P. Jackson and Oliver G. Schmidt

      Article first published online: 25 APR 2014 | DOI: 10.1002/adhm.201300678

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      Rolled-up transparent microtubes are shown to serve as cell culture scaffolds that exactly define the space available for single cell growth. Human U2OS osteosarcoma cells are confined within microtubes of different diameters and the effects of the cell deformation on the integrity of the DNA and cell survival are studied.

  2. Full Papers

    1. Polymeric-Gold Nanohybrids for Combined Imaging and Cancer Therapy

      Antonio Topete, Manuel Alatorre-Meda, Eva M. Villar-Alvarez, Susana Carregal-Romero, Silvia Barbosa, Wolfgang J. Parak, Pablo Taboada and Víctor Mosquera

      Article first published online: 25 APR 2014 | DOI: 10.1002/adhm.201400023

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      Polymeric-Gold nanohybrids (PGNH NPs) co-loaded with doxorubicin and SPIONs, and functionalized with folic acid are tested for multimodal therapy (photothermal- and chemo-therapy) and simultaneous magnetic resonance and optical imaging. Light-triggered drug release is demonstrated as well as an enhanced cellular uptake by effect of folic acid and external magnetic field. PGNH NPs are highly selective and show synergistic cytotoxic effect.

    2. Gel Scaffolds of BMP-2-Binding Peptide Amphiphile Nanofibers for Spinal Arthrodesis

      Sungsoo S. Lee, Erin L. Hsu, Marco Mendoza, Jason Ghodasra, Michael S. Nickoli, Amruta Ashtekar, Mahesh Polavarapu, Jacob Babu, Rehan M. Riaz, Joseph D. Nicolas, David Nelson, Sohaib Z. Hashmi, Start R. Kaltz, Jeffrey S. Earhart, Bradley R. Merk, Jeff S. McKee, Shawn F. Bairstow, Ramille N. Shah, Wellington K. Hsu and Samuel I. Stupp

      Article first published online: 22 APR 2014 | DOI: 10.1002/adhm.201400129

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      Supramolecular nanofibers presenting BMP-2-binding epitopes on the surface exhibit superior spinal fusion rates in rats, effectively decreasing the therapeutic dose of BMP-2 by 10-fold. Importantly, the bioactive nanofibers elicit 42% fusion rate without the addition of exogenous BMP-2.

  3. Communications

    1. Carbon Nanotube Composites as Multifunctional Substrates for In Situ Actuation of Differentiation of Human Neural Stem Cells

      John Landers, Jeffrey T. Turner, Greg Heden, Aaron L. Carlson, Neal K. Bennett, Prabhas V. Moghe and Alexander V. Neimark

      Article first published online: 22 APR 2014 | DOI: 10.1002/adhm.201400042

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      For the first time, single-walled carbon nanotube–polymer composites are shown to enhance human neural stem cell (NSC) differentiation with electrical stimulation. The substrates are electrically conductive, mechanically robust, and highly biocompatible with human NSC cultures. The substrate's fibrous topography mimicking the extracellular matrix enhances neuronal lineage expression and electro-conductivity provides means for controlled stimulation of neuronal maturation.

    2. A Platform for Controlled Dual-Drug Delivery to the Retina: Protective Effects against Light-Induced Retinal Damage in Rats

      Nobuhiro Nagai, Hirokazu Kaji, Hideyuki Onami, Yuki Katsukura, Yumi Ishikawa, Zhaleh Kashkouli Nezhad, Kaori Sampei, Satoru Iwata, Shuntaro Ito, Matsuhiko Nishizawa, Toru Nakazawa, Noriko Osumi, Yukihiko Mashima and Toshiaki Abe

      Article first published online: 19 APR 2014 | DOI: 10.1002/adhm.201400114

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      Controlled transscleral co-delivery of two drugs, edaravone (EDV) and unoprostone (UNO), using a platform that comprises a microfabricated reservoir, controlled-release cover, and drug formulations, which are made of photopolymerized poly(ethyleneglycol) dimethacrylates, shows synergistic retinal neuroprotection against light injury in rats when compared with single-drug-loaded devices. The device would offer a safer therapeutic method than intravitreal injections for retinal disease treatments.

    3. Small-Dose-Sensitive X-Ray Image Pixel with HgI2 Photoconductor and Amorphous Oxide Thin-Film Transistor

      Jae Chul Park, Pyo Jin Jeon, Jin Sung Kim and Seongil Im

      Article first published online: 19 APR 2014 | DOI: 10.1002/adhm.201400077

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      A new X-ray image sensor is demonstrated with oxide thin-film transistor backplane and HgI2 sensing material. It displays outstanding image quality under a low X-ray exposure and a low electric field. It is promising as a state-of-the-art device to realize highly resolved images at a low X-ray dose for a variety of medical X-ray imaging applications.

  4. Full Papers

    1. Bioreducible Carboxymethyl Dextran Nanoparticles for Tumor-Targeted Drug Delivery

      Thavasyappan Thambi, Dong Gil You, Hwa Seung Han, V. G. Deepagan, Sang Min Jeon, Yung Doug Suh, Ki Young Choi, Kwangmeyung Kim, Ick Chan Kwon, Gi-Ra Yi, Jun Young Lee, Doo Sung Lee and Jae Hyung Park

      Article first published online: 17 APR 2014 | DOI: 10.1002/adhm.201300691

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      Bioreducible nanoparticles bearing the disulfide bond are developed for the site-specific delivery of poorly water-soluble anticancer drugs at the tumor microenvironment. The nanoparticles are composed of hydrophilic carboxymethyl dextran and hydrophobic bile acid with an intervening disulfide bond. The hydrophilic shells of nanoparticles allow their prolonged circulation in the bloodstream, whereas the bioreducible disulfide bonds trigger the drug release inside the tumor cells after internalization of nanoparticles.

    2. Selection of Functional Human Sperm with Higher DNA Integrity and Fewer Reactive Oxygen Species

      Waseem Asghar, Vanessa Velasco, James L. Kingsley, Muhammad S. Shoukat, Hadi Shafiee, Raymond M. Anchan, George L. Mutter, Erkan Tüzel and Utkan Demirci

      Article first published online: 17 APR 2014 | DOI: 10.1002/adhm.201400058

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      Conventional sperm sorting methods employed in reproductive clinics to treat infertile couples involve centrifugation steps that damage sperm morphology and produce reactive oxygen species (ROS) and DNA fragmentation. Here, a centrifugation-free high-throughput sperm sorting assay that rapidly isolates functional sperm with high DNA integrity and fewer ROS is presented.

    3. Injectable Colloidal Gold in a Sucrose Acetate Isobutyrate Gelating Matrix with Potential Use in Radiation Therapy

      Rasmus I. Jølck, Tina Binderup, Anders E. Hansen, Jonas B. Scherman, Per Munch af Rosenschold, Andreas Kjær and Thomas L. Andresen

      Article first published online: 15 APR 2014 | DOI: 10.1002/adhm.201300668

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      A liquid injectable fiducial marker (nanogel) based on acylated sucrose and PEGylated gold nanoparticles with potential use in image-guided radiation therapy is evaluated in vitro and in vivo. The excellent X-ray contrast, high stability in vivo, high biocompatibility, and ease of administration make it a promising platform for use in radiation therapy.

  5. Communications

    1. The Aspect Ratio of Nanoparticle Assemblies and the Spatial Arrangement of Ligands can be Optimized to Enhance the Targeting of Cancer Cells

      Amy M. Wen and Nicole F. Steinmetz

      Article first published online: 14 APR 2014 | DOI: 10.1002/adhm.201400141

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      Two are better than one: A novel, bottom-up approach using virus-based nanoparticles is developed for the synthesis of dimers and assemblies up to an aspect ratio of 8. Cell uptake is shown to depend on nanoparticle shape and is enhanced for dimers compared with single particles. Symmetrical rather than topo-selective presentation of RGD peptides further enhances cancer cell targeting.

  6. Full Papers

    1. Synthesis and 3D Printing of Biodegradable Polyurethane Elastomer by a Water-based Process for Cartilage Tissue Engineering Applications

      Kun-Che Hung, Ching-Shiow Tseng and Shan-hui Hsu

      Article first published online: 14 APR 2014 | DOI: 10.1002/adhm.201400018

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      Nanoelastomers in the form of biodegradable polyurethanes (PU) nanoparticles (NPs) are successfully synthesized by a water-based process. Elastic scaffolds are manufactured from the water dispersion of PU NPs by 3D printing. The green process generates a highly elastic scaffold with good cytocompatibility. The water-based 3D printing platform offers an exciting opportunity to fabricate nontoxic scaffolds for biomedical applications.

    2. Cryogel Micromechanics Unraveled by Atomic Force Microscopy-Based Nanoindentation

      Petra B. Welzel, Jens Friedrichs, Milauscha Grimmer, Steffen Vogler, Uwe Freudenberg and Carsten Werner

      Article first published online: 14 APR 2014 | DOI: 10.1002/adhm.201400102

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      Direct experimental access to the local, cell-instructive mechanical properties of macroporous cryogel scaffolds is important to control cellular responses in tissue engineering applications. In this study, an atomic force microscopy-based nanoindentation approach is adapted to quantify, for the first time, microscale Young's moduli of a set of biohybrid glycosaminoglycan–poly(ethylene glycol) cryo­gels, enabling an extended physicochemical characterization of these promising 3D biomaterials.

    3. In Situ Generation of Tunable Porosity Gradients in Hydrogel-Based Scaffolds for Microfluidic Cell Culture

      Aswan Al-Abboodi, Ricky Tjeung, Pauline M. Doran, Leslie Y. Yeo, James Friend and Peggy Pui Yik Chan

      Article first published online: 7 APR 2014 | DOI: 10.1002/adhm.201400072

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      Spatial anisotropy is common and critical in in vivo cellular microenvironments. This study demonstrates a novel and facile method for generating continuous porous and chemical gradients in situ in a hydrogel-based microfluidic device. The device allows users to tailor the scaffold structure in situ to study cell responses in a dynamic, biomimetic, anisotropic microenvironment.

    4. Planar Microdevices for Enhanced In Vivo Retention and Oral Bioavailability of Poorly Permeable Drugs

      Hariharasudhan D. Chirra, Ling Shao, Natalie Ciaccio, Cade B. Fox, Jennifer M. Wade, Averil Ma and Tejal A. Desai

      Article first published online: 7 APR 2014 | DOI: 10.1002/adhm.201300676

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      Thin planar microdevices are fabricated with multiple reservoirs using photo­lithography and etching. Unidirectional drug release from microdevice reservoirs results in enhanced permeation and drug absorption. The thin side walls experience low shear stress from gastrointestinal (GI) flow conditions, thereby enhancing microdevice retention/GI drug transit time. These result in an overall increase of oral bioavailability of even poorly permeable drugs.

    5. Peptide Dendrimer–Doxorubicin Conjugate-Based Nanoparticle as an Enzyme-Responsive Drug Delivery System for Cancer Therapy

      Chengyuan Zhang, Dayi Pan, Kui Luo, Wenchuan She, Chunhua Guo, Yang Yang and Zhongwei Gu

      Article first published online: 6 APR 2014 | DOI: 10.1002/adhm.201300601

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      Design, preparation, and characterization of mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle are reported as an enzyme-sensitive drug delivery system for the breast cancer therapy. Both in vitro and in vivo evaluation tumor-bearing mice and healthy mice demonstrate significant increased therapeutic indexes and decreased side effects, indicating the PEGylated peptide dendritic architectures may be used as efficient and safe nanoscale drug delivery vehicles for cancer therapy.

  7. Communications

    1. Endocytic Capsule Sensors for Probing Cellular Internalization

      Kang Liang, Sylvia T. Gunawan, Joseph J. Richardson, Georgina K. Such, Jiwei Cui and Frank Caruso

      Article first published online: 4 APR 2014 | DOI: 10.1002/adhm.201400139

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      A new class of polymer capsules with an in-built endocytic pH-coupled fluorescence switch is reported. These capsules display reversible “on/off” fluorescence in response to cellular pH variations. Using this system, the high-throughput quantification between surface-bound and internalized capsules is demonstrated. This system allows a fundamental study of the interaction between nanoengineered materials and biological systems at a cellular level.

    2. A FRET-Based Dual-Targeting Theranostic Chimeric Peptide for Tumor Therapy and Real-time Apoptosis Imaging

      Kai Han, Yun Liu, Wei-Na Yin, Shi-Bo Wang, Qi Xu, Ren-Xi Zhuo and Xian-Zheng Zhang

      Article first published online: 4 APR 2014 | DOI: 10.1002/adhm.201400020

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      A FRET-based chimeric peptide is reported to mediate specific tumor cell uptaking and apoptosis. Importantly, this chimeric peptide is fluorescence quenched (OFF). Once the apoptosis is initiated and propagated, green fluorescence is lighted up rapidly (ON), achieving simultaneous tumor therapy and real-time apoptosis monitoring.

    3. Biomimetic Interfaces Reveal Activation Dynamics of C-Reactive Protein in Local Microenvironments

      Tatsuro Goda, Peter Kjall, Kazuhiko Ishihara, Agneta Richter-Dahlfors and Yuji Miyahara

      Article first published online: 4 APR 2014 | DOI: 10.1002/adhm.201300625

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      A cell-membrane-mimetic surface with an organic bioelectronic ion pump system creates an in vitro situation that replicates the pathogenic progression on a sensing platform to investigate the molecular dynamics of C-reactive protein (CRP) to its receptor on cell membrane changes by local microenvironments in acute phase of inflammation and infection.

  8. Full Papers

    1. Hybrid Nanotopographical Surfaces Obtained by Biomimetic Mineralization of Statherin-Inspired Elastin-like Recombinamers

      Yuping Li, Xi Chen, Artur J. Ribeiro, Eric D. Jensen, Kyle V. Holmberg, J. Carlos Rodriguez-Cabello and Conrado Aparicio

      Article first published online: 2 APR 2014 | DOI: 10.1002/adhm.201400015

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      Hybrid nanorough surfaces are obtained by coating-etched titanium with statherin-inspired ELRs that controls amorphous calcium mineralization through a biomimetic enzyme-directed process. This method enables the combination and tailoring of physical and biochemical cues to obtain dental and orthopedic implant surfaces and to design functionalized surfaces to investigate and potentially direct the stem cell fate.

  9. Communications

    1. Carbon-Dots-based Two-Photon Visible Nanocarriers for Safe and Highly Efficient Delivery of siRNA and DNA

      Liqin Wang, Xiaoyong Wang, Ashwinkumar Bhirde, Jianbo Cao, Yun Zeng, Xinglu Huang, Yaping Sun, Gang Liu and Xiaoyuan Chen

      Article first published online: 2 APR 2014 | DOI: 10.1002/adhm.201300611

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      A simple and versatile nanoparticulate siRNA and DNA delivery vehicle is reported, based on photonic Cdots by using Alkyl–PEI2k for surface passivation.

  10. Progress Reports

    1. Nanotechnology for the Detection and Therapy of Stroke

      Stuart Kyle and Sikha Saha

      Article first published online: 1 APR 2014 | DOI: 10.1002/adhm.201400009

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      In the Western world, stroke is a leading cause of mortality and long-term morbidity. Current diagnostic and therapeutic options for ischemic stroke are inadequate. Recent advances in nanotechnology have provided promising solutions in helping to address these challenges using nanocarrier systems for diagnostics, molecular imaging and delivery of therapeutics, and nanomaterial scaffolds for neuroregeneration and tissue engineering.

  11. Full Papers

    1. Multifunctional Gold Nanorods for siRNA Gene Silencing and Photothermal Therapy

      Jianliang Shen, Han-Cheon Kim, Chaofeng Mu, Emanuela Gentile, Junhua Mai, Joy Wolfram, Liang-nian Ji, Mauro Ferrari, Zong-wan Mao and Haifa Shen

      Article first published online: 1 APR 2014 | DOI: 10.1002/adhm.201400103

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      Multifunctional polyethylenimine (PEI)–gold nanorods (Au NRs) are designed for delivery of small interfering RNA (siRNA) and thermal therapy. This platform shows anticancer activity, through simultaneous thermal ablation and suppression of oncogene expression. miRNA, messenger RNA; NIR, near infrared.

  12. Communications

    1. A Size-Exclusion Nanocellulose Filter Paper for Virus Removal

      Giorgi Metreveli, Linus Wågberg, Eva Emmoth, Sándor Belák, Maria Strømme and Albert Mihranyan

      Article first published online: 31 MAR 2014 | DOI: 10.1002/adhm.201300641

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      This is the first time a 100% natural, unmodified nanofibrous polymer-based membrane is demonstrated capable of removing viruses solely based on the size-exclusion principle, with log10 reduction value (LRV) ≥ 6.3 as limited by the assay lower detection limit and the feed virus titre, thereby matching the performance of industrial synthetic polymer virus removal filters.

    2. Nanoengineered Particles for Enhanced Intra-Articular Retention and Delivery of Proteins

      Ankur Singh, Rachit Agarwal, Carlos A. Diaz-Ruiz, Nick J. Willett, Peiyi Wang, L. Andrew Lee, Qian Wang, Robert E. Guldberg and Andrés J. García

      Article first published online: 31 MAR 2014 | DOI: 10.1002/adhm.201400051

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      Localized intra-articular delivery of anti-inflammatory proteins can reduce inflammation in osteoarthritis but poses a challenge because of raid clearance within few hours of injection. A new class of polymer is developed that forms self-assembled nanoparticles ranging from 300 to 900 nm and demonstrates particle size dependent prolonged retention in intra-articular joint spaces compared to bolus protein over a period of 14 d.

  13. Full Papers

    1. Using SV119-Gold Nanocage Conjugates to Eradicate Cancer Stem Cells Through a Combination of Photothermal and Chemo Therapies

      Tianmeng Sun, Yi Wang, Yucai Wang, Jinbin Xu, Xin Zhao, Suwanna Vangveravong, Robert H. Mach and Younan Xia

      Article first published online: 26 MAR 2014 | DOI: 10.1002/adhm.201400026

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      Cancer stem cells: A new platform is developed to target breast cancer stem cells by functionalizing the surface of Au nanocages with SV119. The interiors of the nanocages could also be loaded with an anticancer drug to achieve a synergetic effect in eradicating cancer stem cells through a combination of photothermal and chemo therapies.

    2. Multifunctional Skin-Like Electronics for Quantitative, Clinical Monitoring of Cutaneous Wound Healing

      Yoshiaki Hattori, Leo Falgout, Woosik Lee, Sung-Young Jung, Emily Poon, Jung Woo Lee, Ilyoun Na, Amelia Geisler, Divya Sadhwani, Yihui Zhang, Yewang Su, Xiaoqi Wang, Zhuangjian Liu, Jing Xia, Huanyu Cheng, R. Chad Webb, Andrew P. Bonifas, Philip Won, Jae-Woong Jeong, Kyung-In Jang, Young Min Song, Beatrice Nardone, Michael Nodzenski, Jonathan A. Fan, Yonggang Huang, Dennis P. West, Amy S. Paller, Murad Alam, Woon-Hong Yeo and John A. Rogers

      Article first published online: 26 MAR 2014 | DOI: 10.1002/adhm.201400073

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      A skin-like, conformal electronics platform that can softly and reversibly laminate perilesionally at the sites of cutaneous wounds is presented to provide highly accurate, quantitative data of relevance to management of healing cascades in surgical site wounds. The use of this type of “epidermal electronics system” in a clinical setting with human subjects defines a set of procedures in sterilization, reuse, and quantitative measurement.

  14. Communications

    1. Neutralized Nanoparticle Composed of SS-Cleavable and pH-Activated Lipid-Like Material as a Long-Lasting and Liver-Specific Gene Delivery System

      Masami Ukawa, Hidetaka Akita, Yasuhiro Hayashi, Ryohei Ishiba, Kota Tange, Masaya Arai, Kazuhiro Kubo, Yuriko Higuchi, Kazunori Shimizu, Satoshi Konishi, Mitsuru Hashida and Hideyoshi Harashima

      Article first published online: 26 MAR 2014 | DOI: 10.1002/adhm.201300629

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      Charge-neutralized lipid envelope-type nanoparticles formed with SS-cleavable and pH-activated lipid-like materials (ssPalm) accumulate rapidly in the liver without forming aggregates in the blood circulation, and result in a liver-specific gene expression for a long duration (>2 weeks) with neither immunological responses nor hepatotoxicity after intraveneous administration, when it carries pDNA free from CpG-motifs.

  15. Full Papers

    1. Phosphorylcholine-Coated Semiconducting Polymer Nanoparticles as Rapid and Efficient Labeling Agents for In Vivo Cell Tracking

      Kanyi Pu, Adam J. Shuhendler, Maija P. Valta, Lina Cui, Matthias Saar, Donna M. Peehl and Jianghong Rao

      Article first published online: 25 MAR 2014 | DOI: 10.1002/adhm.201300534

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      Phosphorylcholine-coated near-infrared semiconducting polymer nanoparticles are developed to possess rapid cell internalization, high tolerance to reactive oxygen species, and sufficient optical tissue penetration depth. These nanoparticles can be used as universal fluorescent labeling agents for long-term tracking of primary cancer cells in living animals.

    2. Soft Robotic Concepts in Catheter Design: an On-Demand Fouling-Release Urinary Catheter

      Vrad Levering, Qiming Wang, Phanindhar Shivapooja, Xuanhe Zhao and Gabriel P. López

      Article first published online: 25 MAR 2014 | DOI: 10.1002/adhm.201400035

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      A new biofouling release method to reduce device infection removes biofilm from the previously inaccessible urinary catheter lumen in proof-of-concept prototypes. It is discovered that mature crystalline biofilms debond from elastomer substrates upon actuation via strain to the substrate, and increasing strain rate increases the efficiency of biofilm detachment.

    3. Functional Core/Shell Drug Nanoparticles for Highly Effective Synergistic Cancer Therapy

      Wei Li, Xiujuan Zhang, Mengjiao Zhou, Baishun Tian, Caitong Yu, Jiansheng Jie, Xiaojun Hao and Xiaohong Zhang

      Article first published online: 25 MAR 2014 | DOI: 10.1002/adhm.201300577

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      High drug-loading content gold-­nanoshelled drug nanoparticles are developed with combination of photothermal therapy and chemotherapy for highly effective cancer therapy. 100% in vivo tumor elimination without tumor recurrence is achieved at a low-laser power density of 1 W cm2 with low systematic toxicity.

  16. Communications

    1. Multifunctional PEGylated Multiwalled Carbon Nanotubes for Enhanced Blood Pool and Tumor MR Imaging

      Shihui Wen, Qinghua Zhao, Xiao An, Jingyi Zhu, Wenxiu Hou, Kai Li, Yunpeng Huang, Mingwu Shen, Wei Zhu and Xiangyang Shi

      Article first published online: 24 MAR 2014 | DOI: 10.1002/adhm.201300631

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      Long-circulating multifunctional Gd(III)-loaded multiwalled carbon nanotubes (MWCNTs) modified with polyethylene glycol are designed and synthesized. The formed MWCNTs are water-dispersible, stable, and have good cytocompatibility and antifouling property. With the low r 2/r 1 relaxivity ratio and relatively long blood circulation time, the multifunctional MWCNTs are able to be used as a platform for enhanced blood pool and tumor MR imaging.

  17. Full Papers

    1. Mesoporous Silica-Coated Plasmonic Nanostructures for Surface-Enhanced Raman Scattering Detection and Photothermal Therapy

      Jianping Yang, Dengke Shen, Lei Zhou, Wei Li, Jianwei Fan, Ahmed Mohamed El-Toni, Wei-xian Zhang, Fan Zhang and Dongyuan Zhao

      Article first published online: 24 MAR 2014 | DOI: 10.1002/adhm.201400053

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      Hybrid plasmonic-mesoporous silica nanocarriers with controllable SPR peaks from 500 to 790 nm are fabricated through spatially confined galvanic replacement approach for surface-enhanced Raman scattering detection and photothermal therapy. Such “simultaneous” diagnosis offers a protocol to specifically guide and focus in the cancer cell or tumor area with Raman signals to realize the targeted photothermal therapy.

  18. Communications

    1. The Role of Surface Functionality in Nanoparticle Exocytosis

      Chang Soo Kim, Ngoc D. B. Le, Yuqing Xing, Bo Yan, Gulen Yesilbag Tonga, Chaekyu Kim, Richard W. Vachet and Vincent M. Rotello

      Article first published online: 24 MAR 2014 | DOI: 10.1002/adhm.201400001

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      Getting out is just as important for nano­therapeutics as getting in. Exocytosis rates determine residency time in the cell, an important determinant for therapeutic efficacy and also for eventual clearance from the cell. In this study, it is shown that exocytosis efficiency is determined by surface functionality, providing a strategy for optimizing nanocarriers.

    2. You have full text access to this OnlineOpen article
      Assessing Cellular Response to Functionalized α-Helical Peptide Hydrogels

      Nazia Mehrban, Edgardo Abelardo, Alexandra Wasmuth, Kieran L. Hudson, Leanne M. Mullen, Andrew R. Thomson, Martin A. Birchall and Derek N. Woolfson

      Article first published online: 24 MAR 2014 | DOI: 10.1002/adhm.201400065

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      α-Helical peptide hydrogels are decorated with a cell-binding peptide motif (RGDS), which is shown to promote adhesion, proliferation, and differentiation of PC12 cells. Gel structure and integrity are maintained after functionalization. This opens possibilities for the bottom-up design and engineering of complex functional scaffolds for 2D and 3D cell cultures.

  19. Full Papers

    1. Development of Therapeutic Polymeric Nanoparticles for the Resolution of Inflammation

      Suresh Gadde, Orli Even-Or, Nazila Kamaly, Apoorva Hasija, Philippe G. Gagnon, Krishna H. Adusumilli, Andrea Erakovic, Anoop K. Pal, Xue-Qing Zhang, Nagesh Kolishetti, Jinjun Shi, Edward A. Fisher and Omid C. Farokhzad

      Article first published online: 24 MAR 2014 | DOI: 10.1002/adhm.201300688

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      The development of liver X receptors (LXRs) agonist GW3965-based nanotherapeutics are described and, for the first time, enhanced proresolving activity of nanoparticles containing GW3965 is demonstrated in a zymosan-induced acute peritonitis animal model. GW3965-nanoparticles are more effective than free agonist and the commercial drug dexamethasone in suppressing pro-inflammatory factors and promoting resolution of inflammation in vitro and in vivo.

  20. Communications

    1. Capture and Release of Cancer Cells Based on Sacrificeable Transparent MnO2 Nanospheres Thin Film

      Qinqin Huang, Bolei Chen, Rongxiang He, Zhaobo He, Bo Cai, Junhua Xu, Weiyi Qian, Helen Laiwa Chan, Wei Liu, Shishang Guo, Xing-Zhong Zhao and Jikang Yuan

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300670

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      A CTCs detection assay using transparent MnO2 nanospheres thin films to capture and release of CTCs is reported. The enhanced local topography interaction between extracellular matrix scaffolds and the antibody-coated substrate leads to improved capture efficiency. CTCs captured from artificial blood sample can be cultured and released, represent a new functional material capable of CTCs isolation and culture for subsequent studies.

  21. Full Papers

    1. Biodegradable and Biocompatible Poly(Ethylene Glycol)-based Hydrogel Films for the Regeneration of Corneal Endothelium

      Berkay Ozcelik, Karl D. Brown, Anton Blencowe, Katharina Ladewig, Geoffrey W. Stevens, Jean-Pierre Y. Scheerlinck, Keren Abberton, Mark Daniell and Greg G. Qiao

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201400045

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      Acid-chloride cross-linked poly(ethylene glycol)-based hydrogel films (PHFs) support the attachment and proliferation of corneal endothelial cells (CECs) with natural morphology and density. In vivo implantation of films reveals ease of implantation, no toxicity, minimal inflammatory responses, and adherence onto the interior corneal surface. Hence, PHFs are excellent candidates for CEC regeneration.

  22. Communications

    1. Influence of Surface-Imprinted Nanoparticles on Trypsin Activity

      António Guerreiro, Alessandro Poma, Kal Karim, Ewa Moczko, Jessica Takarada, Isabel Perez de Vargas-Sansalvador, Nicholas Turner, Elena Piletska, Cristiana Schmidt de Magalhães, Natalia Glazova, Anastasia Serkova, Aleksandra Omelianova and Sergey Piletsky

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300634

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      Here, the modulation of enzyme activity is presented by protein-imprinted nanoparticles produced using a solid-phase approach. Using trypsin as target, binding of the nanoparticles to the enzyme results in its inhibition or in stabilization, depending on the orientation of the immobilized enzyme used during imprinting.

  23. Full Papers

    1. Graphene Oxide Triggers Toll-Like Receptors/Autophagy Responses In Vitro and Inhibits Tumor Growth In Vivo

      Guan-Yu Chen, Chiu-Ling Chen, Hsing-Yu Tuan, Pei-Xiang Yuan, Kuei-Chang Li, Hong-Jie Yang and Yu-Chen Hu

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300591

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      Graphene oxide (GO) itself is sufficient to activate toll-like receptors (TLRs) responses and trigger the downstream autophagy in CT26 colon cancer cells in vitro. Injection of GO into mice bearing CT26 colon cancer can elicit autophagy, enhance cell death, and immune cell infiltration, leading to the suppressed tumor progression in vivo.

    2. Particle-Stabilized Emulsion Droplets for Gravity-Mediated Targeting in the Posterior Segment of the Eye

      Yoo C. Kim, Henry F. Edelhauser and Mark R. Prausnitz

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300696

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      Particle-stabilized emulsion droplets with a high-density core can be used to deliver particles as large as 200 nm to specific sites within the posterior segment of the eye based on gravity-mediated targeting.

    3. Polypeptide-Based “Smart” Micelles for Dual-Drug Delivery: A Combination Study of Experiments and Simulations

      Lili Chen, Tao Jiang, Chunhua Cai, Liquan Wang, Jiaping Lin and Xuguang Cao

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300638

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      A dual-drug-loaded micelle is designed and constructed by PPO-b-PBLG-b-PEG triblock terpolymers. DOX is chemically conjugated to PBLG block via a hydrazone bond, while Nap is encapsulated in micelle core physically. The two loaded drugs exhibit controllable release behaviors with different mechanisms, and such a system is promising in the application of combined therapy.

  24. Communications

    1. Gold Nanoparticles Displaying Tumor-Associated Self-Antigens as a Potential Vaccine for Cancer Immunotherapy

      Sukyung Ahn, In-Hyun Lee, Sukmo Kang, Daejin Kim, Minsuk Choi, Phei Er Saw, Eui-Cheol Shin and Sangyong Jon

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300597

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      Golden Vaccine for Cancers. Gold nanoparticles enable efficient antigen delivery to dendritic cells and then activate the cells to facilitate cross-presentation, inducing antigen-specific cytotoxic T-lymphocyte responses for effective cancer therapy.

  25. Full Papers

    1. Smart pH-Responsive Nanocarrier Based on Nano-Graphene Oxide for Combined Chemo- and Photothermal Therapy Overcoming Drug Resistance

      Liangzhu Feng, Kunyang Li, Xiaoze Shi, Min Gao, Jian Liu and Zhuang Liu

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300549

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      A smart pH-responsive drug delivery system is designed using nano-graphene oxide, which is responsive to the tumor microenvironmental pH and shows an excellent ability in overcoming multidrug resistance of cancer cells. A combined chemo- and photothermal therapy is further demonstrated by utilizing the strong near-infrared absorbance of graphene, achieving a synergistic effect in killing drug-resistant cancer cells.

    2. Effective Nanoparticle-based Gene Delivery by a Protease Triggered Charge Switch

      Torben Gjetting, Rasmus Irming Jølck and Thomas Lars Andresen

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300503

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      A novel liposomal gene delivery vehicle is developed involving a protease-dependent detachment of a protective PEG coat. Protease digestion causes charge reversion acting as a molecular trigger. A combination of constitutive and titratable cationic lipid facilitates efficient loading of genetic material and endosomal escape leading to highly efficient transfection. The system has potential for therapeutic use with intravenous administration.

    3. The Control of Mesenchymal Stem Cell Differentiation Using Dynamically Tunable Surface Microgrooves

      Tao Gong, Kun Zhao, Guang Yang, Jinrong Li, Hongmei Chen, Yuping Chen and Shaobing Zhou

      Article first published online: 20 MAR 2014 | DOI: 10.1002/adhm.201300692

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      A dynamically tunable smart topography surface is developed to mimic the endo­genous cell culture microenvironment. By changing the surface topographic features and the resultant mechanical forces, we effectively direct stem cell to specifically differentiate towards myogenic lineage in the absence of any induction factors.

  26. Communications

    1. Lipid-Like Nanomaterials for Simultaneous Gene Expression and Silencing In Vivo

      Yizhou Dong, Ahmed A. Eltoukhy, Christopher A. Alabi, Omar F. Khan, Omid Veiseh, J. Robert Dorkin, Sasilada Sirirungruang, Hao Yin, Benjamin C. Tang, Jeisa M. Pelet, Delai Chen, Zhen Gu, Yuan Xue, Robert Langer and Daniel G. Anderson

      Article first published online: 13 MAR 2014 | DOI: 10.1002/adhm.201400054

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      New lipid-like nanomaterials are developed to simultaneously regulate expression of multiple genes. Self-assembled nanoparticles are capable of efficiently encapsulating pDNA and siRNA. These nanoparticles are shown to induce simultaneous gene expression and silencing both in vitro and in vivo.

  27. Full Papers

    1. Magnetic Core–Shell Nanocapsules with Dual-Targeting Capabilities and Co-Delivery of Multiple Drugs to Treat Brain Gliomas

      Jen-Hung Fang, Yen-Ho Lai, Tsung-Lang Chiu, You-Yin Chen, Shang-Hsiu Hu and San-Yuan Chen

      Article first published online: 13 MAR 2014 | DOI: 10.1002/adhm.201300598

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      Magnetic double emulsion capsules (MDCs) equipped with dual-targeting modalities of lactoferrin and magnetic guidance can achieve the efficacious therapy and reduce the side effect by enhancing the cumulative amount and cell internalization. Once MDCs entrapped in lysosome, doxorubicin, and curcumin can be simultaneously released to overcome multidrug resistance and inhibit the tumor growth of brain glioma through synergistic therapy.

  28. Progress Reports

    1. Injectable Chitosan-based Scaffolds in Regenerative Medicine and their Clinical Translatability

      Mina Mekhail and Maryam Tabrizian

      Article first published online: 10 MAR 2014 | DOI: 10.1002/adhm.201300586

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      Injectable chitosan scaffolds (ICS) possess many desirable properties that make them excellent candidates for regenerative medicine applications. The different triggers used to induce ICS gelation are presented. The uses of ICS in four regenerative medicine applications are discussed. Finally, a critique of the ICS literature and suggestions on what is needed to improve clinical translation is provided.

  29. Full Papers

    1. Reconstruction of Vascular Structure with Multicellular Components Using Cell Transfer Printing Methods

      Yu Bin Lee, Indong Jun, Seongwoo Bak, Young Min Shin, Youn-Mook Lim, Hansoo Park and Heungsoo Shin

      Article first published online: 7 MAR 2014 | DOI: 10.1002/adhm.201300548

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      Natural vessels have concentric structure that is composed of three different layers (tunica adventitia, tunica media, tunica intima). Cell transfer printing method is developed, which can deliver cell mono­layer on target substrate to mimic the vascular structure. A construct with multicellular components is fabricated by stamping monolayers of vessel-forming cells on nanofiber substrate and rolling.

    2. Effects of GDNF-Loaded Injectable Gelatin-Based Hydrogels on Endogenous Neural Progenitor Cell Migration

      Deniece Fon, Aswan Al-Abboodi, Peggy P. Y. Chan, Kun Zhou, Peter Crack, David I. Finkelstein and John S. Forsythe

      Article first published online: 4 MAR 2014 | DOI: 10.1002/adhm.201300287

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      An injectable gelatin-based hydrogel is targeted towards the adult rat subventricular zone in an attempt to attract neural progenitors towards the implant. GDNF encapsulation and porosity within the hydrogel prevent glial scar formation, moreover, neuroblasts were attracted to the hydrogels 7 d after implantation. The figure shows neuroblasts (green) migrating from the lateral ventricle (LV) to the implant (*).

  30. Communications

    1. Neuritogenic Surfaces Using Natural Product Analogs

      Patrick Burch, Fabian Schmid and Karl Gademann

      Article first published online: 4 MAR 2014 | DOI: 10.1002/adhm.201300671

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      Neuritogenic surfaces are generated by a simple dip-coating procedure, as glass slides are coated with a neurotrophin-like small organic molecule in the presence of a collagen matrix. The surfaces retain their biological activity for multiple cycles and the protocol is suitable for various substrates and coating conditions.

    2. You have full text access to this OnlineOpen article
      Ionic Liquid Gel-Assisted Electrodes for Long-Term Cutaneous Recordings

      Pierre Leleux, Camryn Johnson, Xenofon Strakosas, Jonathan Rivnay, Thierry Hervé, Róisín M. Owens and George G. Malliaras

      Article first published online: 4 MAR 2014 | DOI: 10.1002/adhm.201300614

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      The integration of an ionic liquid gel on conformal electrodes is investigated for applications in long-term cutaneous recordings. Electrodes made of Au and the conducting polymer PEDOT:PSS coated with the gel show a low impedance in contact with the skin that maintains a steady value over several days, paving the way for non-invasive, long-term monitoring of human electrophysiological activity.

  31. Reviews

    1. Tumor-Targeting Multifunctional Nanoparticles for siRNA Delivery: Recent Advances in Cancer Therapy

      Sook Hee Ku, Kwangmeyung Kim, Kuiwon Choi, Sun Hwa Kim and Ick Chan Kwon

      Article first published online: 28 FEB 2014 | DOI: 10.1002/adhm.201300607

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      Nanotechnology offers an ideal opportunity to develop the efficient siRNA delivery system for cancer therapy. In this Review, tumor-targeting strategies of nano­particles, passive targeting and active targeting, are summarized. The recent advances in siRNA nanocarriers for cancer treatment, containing multifunctionalities, are also highlighted.

    2. Bioactive Supramolecular Peptide Nanofibers for Regenerative Medicine

      Elif Arslan, I. Ceren Garip, Gulcihan Gulseren, Ayse B. Tekinay and Mustafa O. Guler

      Article first published online: 25 FEB 2014 | DOI: 10.1002/adhm.201300491

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      Supramolecular peptide nanofiber systems have been used as synthetic scaffolds in regenerative medicine applications due to their tailorable properties and ability to mimic extracellular matrix proteins. This Review covers structural and biochemical properties of the self-assembled peptide nanofibers to alter cellular behavior including cell adhesion, proliferation, and/or differentiation.

  32. Full Papers

    1. Structural and Biochemical Modification of a Collagen Scaffold to Selectively Enhance MSC Tenogenic, Chondrogenic, and Osteogenic Differentiation

      Steven R. Caliari and Brendan A. C. Harley

      Article first published online: 25 FEB 2014 | DOI: 10.1002/adhm.201300646

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      Selective modification to microstructural features of a collagen-GAG scaffold is used to direct mesenchymal stem cell differentiation down multiple lineages for osteotendinous interface repair. Combinations of structural and biochemical cues to promote selective tenogenic, osteogenic, and chondrogenic lineage specification are identified to support ongoing development of biomaterial platforms for complex orthopedic tissue engineering challenges.

    2. Characterization of Conjugated Polymer Actuation under Cerebral Physiological Conditions

      Eugene Dariush Daneshvar and Elisabeth Smela

      Article first published online: 24 FEB 2014 | DOI: 10.1002/adhm.201300610

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      To explore the potential use of conjugated polymer actuators within brain tissue, actuation is characterized at body temperature in artificial cerebrospinal fluid. Despite the mixture of exchanged ions, motion remains monotonic. Applications may include guiding the insertion of neural probes or modulating the position of electrode sites.

  33. Communications

    1. Peptide-Directed Spatial Organization of Biomolecules in Dynamic Gradient Scaffolds

      Lesley W. Chow, Astrid Armgarth, Jean-Philippe St-Pierre, Sergio Bertazzo, Cristina Gentilini, Claudia Aurisicchio, Seth D. McCullen, Joseph A. M. Steele and Molly M. Stevens

      Article first published online: 24 FEB 2014 | DOI: 10.1002/adhm.201400032

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      Specific binding peptides are used to spatially organize biomolecule gradients within an electrospun fiber scaffold. Different biomolecule-binding peptide–polymer conjugates are sequentially co-electrospun with a fiber-forming host polymer to generate opposing gradients of peptide functionalization. The binding peptides specifically and non-covalently guide the spatial arrangement of biomolecules into dynamic gradients within the scaffold, mimicking biological gradients found in native tissues.

  34. Full Papers

    1. Fabrication of Barium- and Strontium-Doped Silica/Titania Hollow Nanoparticles and Their Synergetic Effects on Promoting Neuronal Differentiation by Activating ERK and p38 Pathways

      Sojin Kim, Yoonsun Jang, Wan-Kyu Oh, Chanhoi Kim and Jyongsik Jang

      Article first published online: 21 FEB 2014 | DOI: 10.1002/adhm.201300572

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      The barium- and strontium-doped hollow nanoparticles are fabricated using sonication medicated etching and redeposition method with alkaline-earth metal hydroxide solution. PC12 cells co-incubated with the nanoparticles and nerve growth factor (NGF) demonstrate enhanced neuronal differentiation. To deliver NGF into cells efficiently, the nanoparticles are further applied to encapsulate NGF, which exhibits most enhancements in neuronal differentiation.

  35. Communications

    1. Enhanced Intracellular siRNA Delivery Using Bioreducible Lipid-Like Nanoparticles

      Ming Wang, Kyle Alberti, Antonio Varone, Dimitria Pouli, Irene Georgakoudi and Qiaobing Xu

      Article first published online: 20 FEB 2014 | DOI: 10.1002/adhm.201400039

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      A new library of lipid-like nanoparticles (lipidoids) comprising disulfide bond is developed for siRNA delivery. Bioreducible lipidoids deliver siRNA with greater efficiency than nonbioreducible lipidoids with similar chemical structures. A siRNA release investigation, as well as an intracellular siRNA trafficking study, reveals that the degradation of bioreducible lipidoid in a strongly reductive intracellular environment boosts siRNA release and enhances siRNA gene knockdown efficiency.

    2. Supramolecular Nanofibrils Inhibit Cancer Progression In Vitro and In Vivo

      Yi Kuang, Xuewen Du, Jie Zhou and Bing Xu

      Article first published online: 20 FEB 2014 | DOI: 10.1002/adhm.201300645

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      Self-assembly of small peptide derivatives affords supramolecular nanofibrils that possess characteristic feature of amyloid oligomers. Acting as de novo amyloid oligomers, the nanofibrils effectively inhibit the tumor progression both in vitro and in vivo, which demonstrates a new type of anticancer approach and may provide new insights for inverse comorbidity between cancer and neurodegenerative diseases.

    3. Modification of Biomaterials with a Self-Protein Inhibits the Macrophage Response

      Yoon Kyung Kim, Richard Que, Szu-Wen Wang and Wendy F. Liu

      Article first published online: 20 FEB 2014 | DOI: 10.1002/adhm.201300532

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      A biomaterial that inhibits the host immune response by displaying an endo­genously expressed immunomodulatory molecule, CD200. Immobilization of CD200 onto biomaterial surfaces effectively suppresses macrophage activation and reduces inflammatory response to subcutaneously implanted materials.

    4. Gadolinium-Enriched Polyaniline Particles (GPAPs) for Simultaneous Diagnostic Imaging and Localized Photothermal Therapy of Epithelial Cancer

      Taeksu Lee, Doyeon Bang, Yeonji Park, Sun Hee Kim, Jihye Choi, Joseph Park, Donghun Kim, Eunkyoung Kim, Jin-Suck Suh, Yong-Min Huh and Seungjoo Haam

      Article first published online: 18 FEB 2014 | DOI: 10.1002/adhm.201300636

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      By loading GdIII inside NIR-absorbing polyaniline nanostructures, a novel diagnostic and photothermal agent with enhanced MR sensitivity, targeting ability, and photothermal ability to treat epithelial cancer is developed.

  36. Full Papers

    1. Enzyme-Responsive Cell-Penetrating Peptides Conjugated Mesoporous Silica Quantum Dots Nanocarriers for Controlled Release of Nucleus-Targeted Drug Molecules and Real-Time Intracellular Fluorescence Imaging of Tumor Cells

      Jinming Li, Fang Liu, Qing Shao, Yuanzeng Min, Marianne Costa, Edwin K. L. Yeow and Bengang Xing

      Article first published online: 18 FEB 2014 | DOI: 10.1002/adhm.201300613

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      A set of mesoporous silica (mSiO 2 )-coated quantum dots (QDs) nanocarriers functionalized with enzyme-responsive cell-penetrating peptide sequence is presented to control the targeted delivery of antitumor reagent, doxorubicin (DOX) into the nucleus of tumor cells, and meantime to real-time image the targeting and delivery through QD fluorescence.

    2. Mixed-Charge Nanoparticles for Long Circulation, Low Reticuloendothelial System Clearance, and High Tumor Accumulation

      Xiangsheng Liu, Huan Li, Yangjun Chen, Qiao Jin, Kefeng Ren and Jian Ji

      Article first published online: 18 FEB 2014 | DOI: 10.1002/adhm.201300617

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      Gold nanoparticles (AuNPs) modified with mixed-charge zwitterionic surfaces exhibit long blood circulation time and high tumor uptake in vivo. It shows promise to easily fabricate “stealth” inorganic nanoparticles for biomedical applications by using the simple mixed-charge strategy.

  37. Progress Reports

    1. Nanostructural Systems Developed with Positive Charge Generation to Drug Delivery

      Fei-Fei An, Weipeng Cao and Xing-Jie Liang

      Article first published online: 18 FEB 2014 | DOI: 10.1002/adhm.201300600

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      Positive-charge-generating nanostructures are highly attractive nanocarriers for efficient drug delivery to tumor due to their combined advantages of long blood circulation, passive tumoral accumulation, stimulus-enhanced cell uptake, and intracellular drug release. This Progress Report discusses the design and application of each type of positive-charge-generating nanostructures to drug delivery.

  38. Communications

    1. Nucleotides as Nontoxic Endogenous Endosomolytic Agents in Drug Delivery

      Hana Cho, Yong-Yeon Cho, You Han Bae and Han Chang Kang

      Article first published online: 17 FEB 2014 | DOI: 10.1002/adhm.201400008

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      Nontoxic endogenous nucleotides such as adenosine triphosphate and guanosine triphosphate have secondary phosphate groups, causing proton-buffering capacity and/or hemolytic activity in endolysosomal pH ranges. Nucleotides co-delivered in single polymeric pDNA nanocarrier induce highly enhanced transfection efficiency with negligible cytotoxicity due to their endosomolytic functions.

  39. Full Papers

    1. Track-Etched Magnetic Micropores for Immunomagnetic Isolation of Pathogens

      Melaku Muluneh, Wu Shang and David Issadore

      Article first published online: 17 FEB 2014 | DOI: 10.1002/adhm.201300502

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      A microchip is developed to rapidly and selectively sort magnetically labeled cells from unprocessed suspensions, consisting of a track-etched membrane coated with a soft magnetic film. Track-etched micropores can be fabricated with pore sizes from 30 nm to 100 μm at little cost, enabling this approach to be optimally applied to a wide range of biological targets.

  40. Communications

    1. Magnetic Ligation Method for Quantitative Detection of MicroRNAs

      Monty Liong, Hyungsoon Im, Maulik D. Majmudar, Aaron D. Aguirre, Matthew Sebas, Hakho Lee and Ralph Weissleder

      Article first published online: 14 FEB 2014 | DOI: 10.1002/adhm.201300672

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      A magnetic ligation method is utilized for the detection of microRNAs among a complex biological background without polymerase chain reaction or nucleotide modification. The sandwich probes assay can be adapted to analyze a panel of microRNAs associated with cardiovascular diseases in heart tissue samples.

    2. Prodrug Strategy to Achieve Lyophilizable, High Drug Loading Micelle Formulations Through Diester Derivatives of β-Lapachone

      Xinpeng Ma, Xiumei Huang, Gang Huang, Longshan Li, Yiguang Wang, Xiuquan Luo, David A. Boothman and Jinming Gao

      Article first published online: 14 FEB 2014 | DOI: 10.1002/adhm.201300590

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      β-Lap prodrug micelle strategy improves the formulation properties of β-lap therapeutics. The resulting micelles yield apparent high β-lap solubility (>7 mg mL−1), physical stability, and ability to reconstitute after lyophilization. In the presence of esterase, β-lap prodrugs are efficiently converted into parent drug (i.e., β-lap), resulting in NQO1-dependent lethality of NSCLC cells.

  41. Full Papers

    1. Click Hybridization of Immune Cells and Polyamidoamine Dendrimers

      Leyuan Xu, Olga Yu. Zolotarskaya, W. Andrew Yeudall and Hu Yang

      Article first published online: 13 FEB 2014 | DOI: 10.1002/adhm.201300515

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      Immobilizing highly branched poly­amidoamine (PAMAM) dendrimers to the cell surface represents an innovative method of enhancing cell surface loading capacity to deliver therapeutic and imaging agents. Efficient and selective hybridization of immune cells (e.g., macrophages and dendrimers) on the basis of bioorthogonal chemistry is reported.

    2. Reconstituting Vascular Microenvironment of Neural Stem Cell Niche in Three-Dimensional Extracellular Matrix

      Yoojin Shin, Kisuk Yang, Sewoon Han, Hyun-Ji Park, Yun Seok Heo, Seung-Woo Cho and Seok Chung

      Article first published online: 12 FEB 2014 | DOI: 10.1002/adhm.201300569

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      Neural stem cell (NSC)-vascular niche consisting of a brain vasculature and 3D extracellular matrix (ECM) is reconstituted in microfluidic system. In vivo-like microenvironment reconstituted in this system allows NSCs to adopt physiologically relevant phenotypes through the combined effects of 3D ECM and vasculature. The microfluidic NSC-vascular niche can provide precise temporal control of self-renewal differentiation of NSCs.

    3. Reduction in Wound Bioburden using a Silver-Loaded Dissolvable Microfilm Construct

      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

      Article first published 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.

    4. Three-Dimensional Paper-Based Model for Cardiac Ischemia

      Bobak Mosadegh, Borna E. Dabiri, Matthew R. Lockett, Ratmir Derda, Patrick Campbell, Kevin Kit Parker and George M. Whitesides

      Article first published online: 12 FEB 2014 | DOI: 10.1002/adhm.201300575

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      A paper-based 3D cell culture system recapitulates certain aspects of cardiac ischemia, including gradients of nutrients and migration of fibroblasts. Stacking multiple thin (≈200 μm) layers of paper into thicker (≈1 mm) tissue-like constructs enables precise positioning of different types of cells, tracking of migratory cells between layers, and analysis of cells in specific regions of the stack.

    5. Lung Deposition and Cellular Uptake Behavior of Pathogen-Mimicking Nanovaccines in the First 48 Hours

      Kathleen A. Ross, Shannon L. Haughney, Latrisha K. Petersen, Paola Boggiatto, Michael J. Wannemuehler and Balaji Narasimhan

      Article first published online: 12 FEB 2014 | DOI: 10.1002/adhm.201300525

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      While F1-V-containing polyanhydride nanovaccines have been previously shown to induce protection against lethal challenge, less is known about their initial interactions with immune cells. This work investigates the pulmonary deposition and cellular internalization of intranasally administered F1-V in conjunction with polyanhydride nanoparticles or MPLA, demonstrating the advantages of prolonged antigen presence together with mild inflammation.

    6. Long-Term Survival of Allograft Murine Islets Coated via Covalently Stabilized Polymers

      Hernán R. Rengifo, Jaime A. Giraldo, Irayme Labrada and Cherie L. Stabler

      Article first published online: 5 FEB 2014 | DOI: 10.1002/adhm.201300573

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      Application of bioorthogonal polymers for cellular encapsulation: Alginate and poly(ethylene glycol) (PEG), functionalized with azide and 1-methyl-2-diphenylphos­phino-terephthalate (MDT), respec­tively, form spontaneous and chemoselective crosslinks via the bioorthogonal Staudinger ligation scheme. These polymers are utilized to generate ultrathin coatings on murine pancreatic islets. Resulting coatings are nontoxic and impart significant immunoprotective effects when transplanted in a full allograft mismatch murine model.

  42. Communications

    1. You have full text access to this OnlineOpen article
      Thermally Switchable Polymers Achieve Controlled Escherichia coli Detachment

      Andrew L. Hook, Chien-Yi Chang, David J. Scurr, Robert Langer, Daniel G. Anderson, Paul Williams, Martyn C. Davies and Morgan R. Alexander

      Article first published online: 4 FEB 2014 | DOI: 10.1002/adhm.201300518

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      The thermally triggered release of up to 96% of attached uropathogenic E. coli is achieved on two polymers with opposite changes in surface wettability upon reduction in temperature. This demonstrates that the bacterial attachment to a surface cannot be explained in terms of water contact angle alone; rather, the surface composition of the polymer plays the key role.

  43. Full Papers

    1. You have full text access to this OnlineOpen article
      Dynamic Monitoring of Salmonella typhimurium Infection of Polarized Epithelia Using Organic Transistors

      Scherrine A. Tria, Marc Ramuz, Miriam Huerta, Pierre Leleux, Jonathan Rivnay, Leslie H. Jimison, Adel Hama, George G. Malliaras and Róisín M. Owens

      Article first published online: 3 FEB 2014 | DOI: 10.1002/adhm.201300632

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      Organic electronic materials have opened the door for the development of low-cost, disposable sensors for cell-based in vitro diagnostics. Here, for the first time, the feasibility of using an organic transistor integrated with a human intestinal cell line for detecting a food-borne enteric pathogen, Salmonella typhimurium, is shown by dynamically measuring changes in ion flow provoked by the bacteria.

  44. Reviews

    1. Biodegradable Thermogelling Polymers: Working Towards Clinical Applications

      Qing Qing Dou, Sing Shy Liow, Enyi Ye, Rajamani Lakshminarayanan and Xian Jun Loh

      Article first published online: 1 FEB 2014 | DOI: 10.1002/adhm.201300627

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      Synthetic thermal responsive hydrogels have found extensive applications for wound healing, drug delivery and controlled release, and scaffold materials in the human body. The development of the next generation of biodegradable thermogels focuses on facile synthetic methods, efficacy of treatment, and tailored multi-functionalities for real applications. The use of biodegradable thermogels as soft biomaterials and their biomedical applications are described in this Review.

  45. Progress Reports

    1. Reactive Oxygen Species-Scavenging Nanomedicines for the Treatment of Oxidative Stress Injuries

      Toru Yoshitomi and Yukio Nagasaki

      Article first published online: 30 JAN 2014 | DOI: 10.1002/adhm.201300576

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      Redox polymer therapeutics using nitroxide radical-containig nanoparticles is developed. pH-sensitive RNPN shows remarkable therapeutic effects on ischemia–reperfusion injuries after its intravenous administration. On the contrary, the pH-insensitive RNPO accumulates in the mucosa and inflamed areas of the gastrointestinal tract after oral administration without uptake in blood, resulting in remarkable therapeutic effects on colitis and small intestinal inflammation.

    2. Injectable Cell Constructs Fabricated via Culture on a Thermoresponsive Methylcellulose Hydrogel System for the Treatment of Ischemic Diseases

      Chieh-Cheng Huang, Zi-Xian Liao, Ding-Yuan Chen, Chun-Wen Hsiao, Yen Chang and Hsing-Wen Sung

      Article first published online: 27 JAN 2014 | DOI: 10.1002/adhm.201300605

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      By employing a thermoresponsive methylcellulose hydrogel system, various injectable cell constructs are fabricated, including cell sheet fragments, cell bodies, core–shell cell bodies, and hypoxic mixed cell bodies, for treating ischemic diseases. This Progress Report discusses in vitro observations and in vivo therapeutic efficacy of each cell construct.

  46. Full Papers

    1. Targeting-Triggered Porphysome Nanostructure Disruption for Activatable Photodynamic Therapy

      Cheng S. Jin, Liyang Cui, Fan Wang, Juan Chen and Gang Zheng

      Article first published online: 27 JAN 2014 | DOI: 10.1002/adhm.201300651

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      Activatable nano-sized beacons for photo­dynamic therapy (PDT): Intact porphysome nanoparticles are inactive for PDT. By incorporating targeting ligands (e.g., folate) into porphysome formulation, receptor-mediated endocytosis facilitates the disruption of the nanostructure inside cells, thus switching back on the photo­dynamic activity of the densely packed porphyrins for effective PDT.

  47. Reviews

    1. Engineering Biomolecular Microenvironments for Cell Instructive Biomaterials

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

      Article first published online: 27 JAN 2014 | DOI: 10.1002/adhm.201300603

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      This Review is focused in 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.

  48. Research News

    1. Microfluidics Expands the Zebrafish Potentials in Pharmaceutically Relevant Screening

      Chia-Yuan Chen and Chao-Min Cheng

      Article first published 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.

  49. Full Papers

    1. Clickable, Photodegradable Hydrogels to Dynamically Modulate Valvular Interstitial Cell Phenotype

      Chelsea M. Kirschner, Daniel L. Alge, Sarah T. Gould and Kristi S. Anseth

      Article first published online: 24 JAN 2014 | DOI: 10.1002/adhm.201300288

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      Photolabile hydrogels provide a platform for cell culture where multiple material properties can be regulated in situ both spatially and temporally. The system can be remotely triggered by the user to modulate cell phenotype through the sequential presentation of biophysical signals such as reduction of substrate modulus and presentation of microtopographies.

    2. Electrospun PGS:PCL Microfibers Align Human Valvular Interstitial Cells and Provide Tunable Scaffold Anisotropy

      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

      Article first published 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.

  50. Reviews

    1. Role of Extracellular Matrix Signaling Cues in Modulating Cell Fate Commitment for Cardiovascular Tissue Engineering

      Karina H. Nakayama, Luqia Hou and Ngan F. Huang

      Article first published online: 20 JAN 2014 | DOI: 10.1002/adhm.201300620

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      The current state of the field of cardiovascular engineering using extracellular matrix is reviewed. The differentiation of stem cells towards cardiovascular lineages through modulation of the chemical, spatial, and mechanical properties of ECM substrates is discussed, with a special focus on transdifferentiation/endothelial-to-mesenchymal transformations and therapeutic applications for cardiac patches and vascular grafts.

    2. Delivering Colloidal Nanoparticles to Mammalian Cells: A Nano–Bio Interface Perspective

      Paolo Verderio, Svetlana Avvakumova, Giulia Alessio, Michela Bellini, Miriam Colombo, Elisabetta Galbiati, Serena Mazzucchelli, Jesus Peñaranda Avila, Benedetta Santini and Davide Prosperi

      Article first published online: 20 JAN 2014 | DOI: 10.1002/adhm.201300602

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      Challenges and recent advances in delivering colloidal nanoparticles to mammalian cells are presented. This Review focuses on innovative strategies and established techniques for nanoparticle targeting and delivery to subcellular compartments. The response of cellular environment to nanomaterials is also presented to emphasize the importance to develop novel approaches with the aim to improve the control over nanoparticle transport.

  51. Communications

    1. Hyperthermia-Induced Drug Delivery from Thermosensitive Liposomes Encapsulated in an Injectable Hydrogel for Local Chemotherapy

      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

      Article first published 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 has resulted in a promising candidate for local chemotherapy.

    2. High Aspect Ratio Elongated Microparticles for Enhanced Topical Drug Delivery in Human Volunteers

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

      Article first published 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.

    3. Macromolecular Prodrugs of Ribavirin: Concerted Efforts of the Carrier and the Drug

      Anton A. A. Smith, Benjamin M. Wohl, Mille B. L. Kryger, Natasha Hedemann, Carlos Guerrero-Sanchez, Almar Postma and Alexander N. Zelikin

      Article first published online: 10 JAN 2014 | DOI: 10.1002/adhm.201300637

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      Polymers in tune. Automated parallel polymer synthesis is developed to obtain libraries of macromolecular prodrugs of ribavirin, a broad-spectrum antiviral agent. As many as 10 identified lead polymer conjugates exhibit therapeutic efficacy matching that of the pristine drug and at the same time suppressed the origin of the main side effect of ribavirin.

    4. 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

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

      Article first published 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.

    5. Facile Fabrication of Polyanhydride/Anesthetic Nanoparticles with Tunable Release Kinetics

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

      Article first published 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.

    6. Directed Nerve Regeneration Enabled by Wirelessly Powered Electrodes Printed on a Biodegradable Polymer

      Christopher Martin, Théophile Dejardin, Andrew Hart, Mathis O. Riehle and David R. S. Cumming

      Article first published online: 27 DEC 2013 | DOI: 10.1002/adhm.201300481

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      Wirelessly directed nerve regeneration: inductively powered electrical stimulation circuits on the biodegradable polymer, polycaprolactone, demonstrate directed regeneration of sensory neurons from a dorsal root ganglion. These circuits, produced using a unique transfer printing process, illustrate progress towards the use of electrical stimulation systems on biodegradable materials to improve peripheral nerve repair functional outcomes.

  52. Full Papers

    1. Smart Nanorods for Highly Effective Cancer Theranostic Applications

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

      Article first published 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.

    2. Microneedle-Based Transdermal Sensor for On-Chip Potentiometric Determination of K,+

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

      Article first published 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. Recombinant Human Lactoferrin as a Biomaterial for Bone Tissue Engineering: Mechanism of Antiapoptotic and Osteogenic Activity

      Ashley A. Amini and Lakshmi S. Nair

      Article first published 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.

  53. Communications

    1. High-Density Polymer Microarrays: Identifying Synthetic Polymers that Control Human Embryonic Stem Cell Growth

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

      Article first published 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.

    2. Graphene-Based Patterning and Differentiation of C2C12 Myoblasts

      Piyush Bajaj, Jose A. Rivera, Daniel Marchwiany, Vita Solovyeva and Rashid Bashir

      Article first published online: 18 DEC 2013 | DOI: 10.1002/adhm.201300550

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      This study aims at generating highly aligned functional myotubes using graphene as the underlying scaffold. Graphene not only supports the growth of C2C12 muscle cells but also enhances its differentiation and leads to spontaneous patterning of myotubes.

  54. Full Papers

    1. Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth

      Ming Yang, Tao Yu, Ying-Ying Wang, Samuel K. Lai, Qi Zeng, Bolong Miao, Benjamin C. Tang, Brian W. Simons, Laura M. Ensign, Guanshu Liu, Kannie W.Y. Chan, Chih-Yin Juang, Olcay Mert, Joseph Wood, Jie Fu, Michael T. McMahon, T.-C. Wu, Chien-Fu Hung and Justin Hanes

      Article first published online: 16 DEC 2013 | DOI: 10.1002/adhm.201300519

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      Paclitaxel-encapsulated mucus-penetrating particles (MPP) composed entirely of generally regarded as safe (GRAS) materials effectively bypass the mucus barrier and deliver a sustained level of chemo to cervical tumor tissues in mice, resulting in superior suppression of tumor growth compared with conventional particles. The MPP platform provides a promising approach to local chemotherapy against early-stage cervical cancer, and potentially other cancers at mucosal surfaces

  55. Communications

    1. Whole Blood Cells Loaded with Messenger RNA as an Anti-Tumor Vaccine

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

      Article first published 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.


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