Advanced Healthcare Materials

Cover image for Vol. 3 Issue 7

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

VIEW

  1. 1 - 100
  2. 101 - 103
  1. Full Papers

    1. A Pharmacokinetic Model of a Tissue Implantable Insulin Sensor

      Gili Bisker, Nicole M. Iverson, Jiyoung Ahn and Michael S. Strano

      Article first published online: 31 JUL 2014 | DOI: 10.1002/adhm.201400264

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      An in vivo insulin affinity sensor is modeled and optimized using a full physiological compartmental model for glucose, insulin, and glucagon metabolism. The detection platform is based on fluorescent sensors encapsulated within a hydrogel implanted subcutaneously enabling external optical detection. The correlation between insulin–sensor interaction parameters and hydrogel dimensions is explicated to the sensor response and time lag relative to plasma concentration, providing theoretical grounds for experimental designs.

    2. A Multistep Photothermic-Driven Drug Release System Using Wire-Framed Au Nanobundles

      Doyeon Bang, Taeksu Lee, Jihye Choi, Yeonji Park, Eunkyoung Kim, Yong-Min Huh and Seungjoo Haam

      Article first published online: 19 JUL 2014 | DOI: 10.1002/adhm.201400197

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      Wire-framed Au nanobundles (WNBs) are synthesized for an externally controlled multistep drug release system. WNB consists of randomly oriented and mutually connected Au wires to form a bundle shape. In contrast to conventional nanoparticles that encapsulate a drug on their surface, WNBs preserve the drug payload in the overall inner volume, which provides a drug loading capacity sufficient for cancer therapy.

  2. Reviews

    1. The Bioactivity of Cartilage Extracellular Matrix in Articular Cartilage Regeneration

      Amanda J. Sutherland, Gabriel L. Converse, Richard A. Hopkins and Michael S. Detamore

      Article first published online: 17 JUL 2014 | DOI: 10.1002/adhm.201400165

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      Cartilage matrix as a biomaterial is a particularly promising material for enhanced cartilage regeneration because of the material's ability to provide stem cells with physical attachment sites, mechanical signals, and chemical signals. Cartilage matrix can be derived from both in vitro and tissue sources. Processing methods also differ as the matrix can be either chemically decellularized or physically devitalized.

  3. Communications

    1. Directing Stem Cell Differentiation by Changing the Molecular Mobility of Supramolecular Surfaces

      Ji-Hun Seo, Sachiro Kakinoki, Tetsuji Yamaoka and Nobuhiko Yui

      Article first published online: 10 JUL 2014 | DOI: 10.1002/adhm.201400173

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      The polymer surfaces with a wide range of hydrated surface mobility are developed by a simple deposition method with supramolecular block copolymers. The morphologies of adhering stem cells are greatly dependent on the surface mobility of polymers, and this induces significant changes in the cytoskeletal signaling pathway to direct the downstream stem cell differentiation.

  4. Full Papers

    1. Degradable Hyaluronic Acid/Protamine Sulfate Interpolyelectrolyte Complexes as miRNA-Delivery Nanocapsules for Triple-Negative Breast Cancer Therapy

      Shihua Wang, Minjun Cao, Xiongwei Deng, Xiangqian Xiao, Zhaoxia Yin, Qin Hu, Zhixiang Zhou, Fang Zhang, Ruirui Zhang, Yan Wu, Wang Sheng and Yi Zeng

      Article first published online: 9 JUL 2014 | DOI: 10.1002/adhm.201400222

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      Biodegradable nanocapsules are developed for miRNA delivery based on hyaluronic acid (HA)/protamine sulfate (PS) interpolyelectrolyte complexes (HP-IPECs). Tumor suppressive miR-34a can be efficiently encapsulated into these nanocapsules and targetedly delivered by HP-IPECs into breast cancer cells or breast cancer tissues for miRNA-based therapy against triple-negative breast cancer.

  5. Communications

    1. Collagen Scaffold Arrays for Combinatorial Screening of Biophysical and Biochemical Regulators of Cell Behavior

      Steven R. Caliari, Emily A. Gonnerman, William K. Grier, Daniel W. Weisgerber, Jessica M. Banks, Aurora J. Alsop, Jae-Sung Lee, Ryan C. Bailey and Brendan A. C. Harley

      Article first published online: 2 JUL 2014 | DOI: 10.1002/adhm.201400252

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      Arrays of 3D macroporous collagen scaffolds with orthogonal gradations of structural and biomolecular cues are described. Gradient maker technology is applied to create linear biomolecular gradients within microstructurally distinct sections of a single CG scaffold array. The array set up is used to explore cell behaviors including proliferation and regulation of stem cell fate.

  6. Full Papers

    1. Nanoparticles Based on Star Polymers as Theranostic Vectors: Endosomal-Triggered Drug Release Combined with MRI Sensitivity

      Yang Li, Hien T. T. Duong, Sophie Laurent, Alexandre MacMillan, Renee Megan Whan, Luce Vander Elst, Robert N. Muller, Jinming Hu, Andrew Lowe, Cyrille Boyer and Thomas P. Davis

      Article first published online: 1 JUL 2014 | DOI: 10.1002/adhm.201400164

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      Star polymers bearing gadolinium ions generate contrast in MRI whilst releasing doxorubicin under endosomal pH conditions.

  7. Communications

    1. Electroforming of Implantable Tubular Magnetic Microrobots for Wireless Ophthalmologic Applications

      George Chatzipirpiridis, Olgaç Ergeneman, Juho Pokki, Franziska Ullrich, Stefano Fusco, José A. Ortega, Kartik M. Sivaraman, Bradley J. Nelson and Salvador Pané

      Article first published online: 1 JUL 2014 | DOI: 10.1002/adhm.201400256

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      Magnetic tubular implantable micro­robots are batch fabricated by electroforming. These microdevices can be used in targeted drug delivery and minimally invasive surgery for ophthalmologic applications. These tubular shapes are fitted into a 23-gauge needle enabling sutureless injections. Using a 5-degree-of-freedom magnetic manipulation system, the microimplants are conveniently maneuvered in biological environments. To increase their functionality, the tubes are coated with biocompatible films and can be successfully filled with drugs.

    2. Brain Endothelial Cell Targeting Via a Peptide-Functionalized Liposomal Carrier for Xenon Hyper-CEST MRI

      Matthias Schnurr, Karl Sydow, Honor May Rose, Margitta Dathe and Leif Schröder

      Article first published online: 1 JUL 2014 | DOI: 10.1002/adhm.201400224

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      A nanoparticulate carrier system is used to efficiently deliver a contrast agent for highly sensitive xenon Hyper-CEST MRI. The carrier system not only improves the biocompatibility and solubility of the contrast agent, it also allows selective cell targeting as demonstrated by the discrimination of human brain capillary and aortic endothelial cells.

  8. Full Papers

    1. Intracellular Microenvironment-Responsive Label-Free Autofluorescent Nanogels for Traceable Gene Delivery

      Bingyang Shi, Hu Zhang, Shi Zhang Qiao, Jingxiu Bi and Sheng Dai

      Article first published online: 26 JUN 2014 | DOI: 10.1002/adhm.201400187

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      An intracellular microenvironment-responsive and autofluorescent cationic nanogel is developed as a multifunctional gene delivery carrier. Besides low cytotoxicity, excellent gene loading ability, and high transfection efficiency, the gene delivery course can be tracked in the absence of external fluorescent labeling.

    2. 3D Culture of Tonsil-Derived Mesenchymal Stem Cells in Poly(ethylene glycol)-Poly(l-alanine-co-l-phenyl alanine) Thermogel

      Min Hee Park, Yeonsil Yu, Hyo Jung Moon, Du Young Ko, Han Su Kim, Hyukjin Lee, Kyung Ha Ryu and Byeongmoon Jeong

      Article first published online: 24 JUN 2014 | DOI: 10.1002/adhm.201400140

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      Tonsil-tissue-derived mesenchymal stem cells (TMSCs), as a new resource of adult stem cells, are 3D cultured in poly(ethylene glycol)-poly(l-alanine-co-l-phenyl alanine) hydrogels that are formed by a temperature-sensitive sol-to-gel transition. The TMSCs in the hydrogels pronouncedly undergo chondrogenic differentiation with high expressions of type II collagen and sulfated glycosaminoglycan under in vitro and in vivo conditions.

    3. Directing Valvular Interstitial Cell Myofibroblast-Like Differentiation in a Hybrid Hydrogel Platform

      Jesper Hjortnaes, Gulden Camci-Unal, Joshua D. Hutcheson, Sung Mi Jung, Frederick J. Schoen, Jolanda Kluin, Elena Aikawa and Ali Khademhosseini

      Article first published online: 24 JUN 2014 | DOI: 10.1002/adhm.201400029

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      This study reports the use of a hybrid hydrogel platform composed of methacrylated hyaluronic acid (HAMA) and methacrylated gelatin (GelMA) that maintains a quiescent VIC phenotype in normal culture (NM) conditions but facilitates VIC activation, hallmarked by α-SMA expression, upon exposure to pathological environmental cues. This hydrogel platform may provide for a controllable physiologically relevant microenvironment that could aid in understanding pathobiology of valvular disease.

  9. Communications

    1. The Construction of Tissue-Engineered Blood Vessels Crosslinked with Adenosine-Loaded Chitosan/β-Cyclodextrin Nanoparticles using a Layer-by-Layer Assembly Method

      Wen Chen, Wen Zeng, Yangxiao Wu, Can Wen, Li Li, Ge Liu, Lei Shen, Mingcan Yang, Ju Tan and Chuhong Zhu

      Article first published online: 20 JUN 2014 | DOI: 10.1002/adhm.201400167

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      A tissue-engineered blood vessel (TEBV) modified with CS/β-CD nanoparticles is constructed, effectively controling the release of adenosine, and this type of TEBV can keep open for over 6 months. This study also demonstrates for the first time that adenosine promotes endothelial progenitor cell (EPC) mobilization and homing via energy conversion, achieving rapid endothelialization of TEBV.

  10. Full Papers

    1. ScFv-Decorated PEG-PLA-Based Nanoparticles for Enhanced siRNA Delivery to Her2+ Breast Cancer

      Shuang Dou, Xian-Zhu Yang, Meng-Hua Xiong, Chun-Yang Sun, Yan-Dan Yao, Yan-Hua Zhu and Jun Wang

      Article first published online: 20 JUN 2014 | DOI: 10.1002/adhm.201400037

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      A ScFv-decorated PEG-PLA-based nanoparticle (ScFvHer2-NPsiRNA) is developed for targeted delivery of siRNA to Her2+ breast cancer. With the rationally designed conjugation site, the ScFvHer2-NPsiRNA can specifically bind to Her2+ breast cancer cells, thus enhancing cellular uptake, improving gene downregulation, and elevating cell apoptosis. More importantly, ScFvHer2-NPsiRNA remarkably improves anticancer effects. This research supplies a strategy for targeted RNA interference therapy.

    2. Titrating T-Cell Epitopes within Self-Assembled Vaccines Optimizes CD4+ Helper T Cell and Antibody Outputs

      Rebecca R. Pompano, Jianjun Chen, Emily A. Verbus, Huifang Han, Arthur Fridman, Tessie McNeely, Joel H. Collier and Anita S. Chong

      Article first published online: 13 JUN 2014 | DOI: 10.1002/adhm.201400137

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      Co-assembly of peptide epitopes is used to integrate T-cell epitopes at a range of doses into self-adjuvanting nanofiber vaccines. Helper T-cell activation and differentiation are shown to follow a set of bell-shaped dose-response curves, peaking at different concentrations for different types of helper T cells. Thus, noncovalent co-assembly is a precise approach to generating modular vaccines with tunable properties.

    3. Highly Conductive Stretchable and Biocompatible Electrode–Hydrogel Hybrids for Advanced Tissue Engineering

      Masato Sasaki, Bijoy Chandapillai Karikkineth, Kuniaki Nagamine, Hirokazu Kaji, Keiichi Torimitsu and Matsuhiko Nishizawa

      Article first published online: 10 JUN 2014 | DOI: 10.1002/adhm.201400209

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      Highly conductive and stretchable 2D and 3D hybrids of a poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU) composite with a double-network hydrogel are described. These hybrid platforms retain high conductivity during stretching, bending, storage in water, and autoclaving, together with permeability and biocompatibility, and have immense potential to advance tissue engineering by applying concerted mechanical and electrical cues.

    4. Multimodal Nanoprobes Evaluating Physiological Pore Size of Brain Vasculatures in Ischemic Stroke Models

      Shuyan Zheng, Ying-Ying Bai, Yinzhi Changyi, Xihui Gao, Wenqing Zhang, Yuancheng Wang, Lu Zhou, Shenghong Ju and Cong Li

      Article first published online: 4 JUN 2014 | DOI: 10.1002/adhm.201400159

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      The pore size upper-limit of ischemic vasculatures is measured as 11 nm by quantifying uptakes of nanoprobes with different diameters in stroke mouse models. Penumbra defined as “salvageable” ischemic tissue performs higher nanoprobe uptake than infarct core and normal brain tissues. This work provides a guideline for developing neuroprotectants by utilizing the enhanced blood–brain barrier permeability in ischemic region.

  11. Communications

    1. Glacier Moraine Formation-Mimicking Colloidal Particle Assembly in Microchanneled, Bioactive Hydrogel for Guided Vascular Network Construction

      Min Kyung Lee, Max H. Rich, Artem Shkumatov, Jae Hyun Jeong, Marni D. Boppart, Rashid Bashir, Martha U. Gillette, Jonghwi Lee and Hyunjoon Kong

      Article first published online: 4 JUN 2014 | DOI: 10.1002/adhm.201400153

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      This study demonstrates that a new method to align microparticles releasing bioactive molecules in microchannels of a hydrogel allows the guiding of growth direction and spacing of vascular networks.

  12. Research News

    1. Nanobiotechnology Promotes Noninvasive High-Intensity Focused Ultrasound Cancer Surgery

      Yu Chen, Hangrong Chen and Jianlin Shi

      Article first published online: 4 JUN 2014 | DOI: 10.1002/adhm.201400127

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      As the “bloodless scalpel,” high-intensity focused ultrasound (HIFU) is regarded as one of the most promising and representative noninvasive therapeutic modalities for cancer surgery. This Research News presents the very recent exciting progresses on the elaborate design and fabrication of organic, inorganic, and organic/inorganic hybrid nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues.

  13. Full Papers

    1. A Novel High-Speed Production Process to Create Modular Components for the Bottom-Up Assembly of Large-Scale Tissue-Engineered Constructs

      Omar F. Khan, Derek N. Voice, Brendan M. Leung and Michael V. Sefton

      Article first published online: 3 JUN 2014 | DOI: 10.1002/adhm.201400150

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      Using a high-speed production method based on air shearing and plug flow, small modular tissue building blocks are created and assembled into large-scale tissues. The bottom-up assembly process creates an internal network of perfusion channels through which cell culture medium is perfused. This perfusion keeps interior cells viable. Large liver-shaped and cardiac tissues are built to demonstrate this system's utility.

  14. Reviews

    1. Electrospun Nanofibers-Mediated On-Demand Drug Release

      Menglin Chen, Yan-Fang Li and Flemming Besenbacher

      Article first published online: 30 MAY 2014 | DOI: 10.1002/adhm.201400166

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      Electrospinning generates biomimetic nanofibers as drug delivery devices that are responsive to different stimuli, such as temperature, pH, light, and electric/magnetic field for controlled release of therapeutic substances. Although at its infancy, the mimicry of these stimuli-responsive nanofibers to the function of the living systems includes both the fibrous structural feature and bio-regulation function as an on-demand drug release depot.

  15. Full Papers

    1. Biphasic Ferrogels for Triggered Drug and Cell Delivery

      Christine A. Cezar, Stephen M. Kennedy, Manav Mehta, James C. Weaver, Luo Gu, Herman Vandenburgh and David J. Mooney

      Article first published online: 26 MAY 2014 | DOI: 10.1002/adhm.201400095

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      A new biphasic ferrogel capable of on-demand drug and cell delivery at small device size is presented. Due to their iron oxide gradient particle distribution, biphasic ferrogels demonstrate large deformations and triggered release with significantly reduced iron oxide content and potentially increased biocompatibility. Increased porosity and enhanced mechanical properties also make these ferrogels attractive for biomedical applications.

    2. SERS-Fluorescence Joint Spectral Encoded Magnetic Nanoprobes for Multiplex Cancer Cell Separation

      Zhuyuan Wang, Shenfei Zong, Hui Chen, Chunlei Wang, Shuhong Xu and Yiping Cui

      Article first published online: 26 MAY 2014 | DOI: 10.1002/adhm.201400092

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      A magnetic nanoencoder for multiplex cancer cell separation is presented, using SERS-fluorescence joint spectra encoding (SFJSE). The nano-encoder can specifically capture and separate target cancer cells. This SFJSE-based magnetic nano-encoder greatly facilitates the multiplex, rapid, and accurate cancer cell separation and has a prosperous potential in high-throughput analysis and cancer diagnosis.

    3. Rational Design of Multifunctional Hetero-Hexameric Proteins for Hydrogel Formation and Controlled Delivery of Bioactive Molecules

      Xiaoli Zhang, Hao Zhou, Ying Xie, Chunhua Ren, Dan Ding, Jiafu Long and Zhimou Yang

      Article first published online: 26 MAY 2014 | DOI: 10.1002/adhm.201300660

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      A hetero-hexameric protein with designable multiple binding sites is engineered at the first time. The obtained protein can be used as cross-linkers to form injectable biohybrid hydrogels with controllable mechanical properties. More importantly, the distinct binding sites in the hetero-hexameric proteins also endow the resulting hydrogels with plenty of docking sites for controlled delivery of bioactive molecules.

  16. Progress Reports

    1. Microfluidic Strategies for Design and Assembly of Microfibers and Nanofibers with Tissue Engineering and Regenerative Medicine Applications

      Michael A. Daniele, Darryl A. Boyd, André A. Adams and Frances S. Ligler

      Article first published online: 23 MAY 2014 | DOI: 10.1002/adhm.201400144

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      Microfluidic fiber fabrication is an emerging strategy for generating synthetic tissue scaffolds and organized cell constructs. Core-sheath flow profiles are generated within a microchannel and solidification of the core fluid continuously produces a polymer microfiber. This system is amenable to an array of polymer chemistries, material composites, and most importantly the incorporation and organization of fragile biomacromolecules and viable cell populations.

  17. Full Papers

    1. Bioengineering a Multicomponent Spinal Motion Segment Construct—A 3D Model for Complex Tissue Engineering

      Tsz Kit Chik, Wai Hon Chooi, Yuk Yin Li, Fu Chak Ho, Hiu Wa Cheng, Tsz Hang Choy, Kam Yim Sze, Keith Kei Dip Luk, Kenneth Man Chi Cheung and Barbara Pui Chan

      Article first published online: 20 MAY 2014 | DOI: 10.1002/adhm.201400192

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      The first bioengineered spinal motion segment construct simulating the native tissue with complex hierarchical organization is fabricated using a module-based integrative approach from mesenchymal stem cells and collagen-based biomaterials. This work represents an important milestone in bioengineering complex tissues and provides a 3D model for future screening of factors stimulating functional remodeling and tissue maturation.

    2. Synergistic Antitumor Effects of Doxorubicin-Loaded Carboxymethyl Cellulose Nanoparticle in Combination with Endostar for Effective Treatment of Non-Small-Cell Lung Cancer

      Mingqiang Li, Zhaohui Tang, Jian Lin, Yu Zhang, Shixian Lv, Wantong Song, Yubin Huang and Xuesi Chen

      Article first published online: 20 MAY 2014 | DOI: 10.1002/adhm.201400108

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      Both angiogenesis and cancer cell proliferation are the main features of tumor tissues. Combinational chemotherapy and antiangiogenic therapy strategy, based on the doxorubicin-containing nanomedicine and antiangiogenic drug endostar, demonstrate remarkably synergistic antitumor and antiangiogenesis effects for the treatment of non-small-cell lung cancer. This synergistic combination provides a convenient, safe, and efficient approach for cancer treatment.

  18. Communications

    1. Injectable Gel Scaffold Based on Biopolymer Microspheres via an Enzymatic Reaction

      Huaping Tan, Ming Fan, Ye Ma, Jiacai Qiu, Xianming Li and Jingxuan Yan

      Article first published online: 15 MAY 2014 | DOI: 10.1002/adhm.201400123

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      Injectable gel scaffolds are produced via an enzymatic reaction and extra electrostatic interactions between enzymatic peptide-functionalized heparin microspheres and a chitosan liquid phase. As a result of the controllability of this approach, the gel scaffolds with double-network structures can render the formulation of a therapeutically effective platform for tissue engineering.

  19. Full Papers

    1. Cardiogenesis of Embryonic Stem Cells with Liquid Marble Micro-Bioreactor

      Fatemeh Sarvi, Kanika Jain, Tina Arbatan, Paul J. Verma, Kerry Hourigan, Mark C. Thompson, Wei Shen and Peggy P. Y. Chan

      Article first published online: 12 MAY 2014 | DOI: 10.1002/adhm.201400138

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      A novel method for inducing embryoid body (EB) formation and spontaneous cardiac mesoderm differentiation is reported. Liquid marble micro-bioreactor is formed by self-assembled polytetrafluoroethylene (PTFE) powder around a droplet of embryonic stem cell (ESC) suspension. ESC aggregates to form uniform EBs and subsequently differentiated into cardiac mesoderm cells without the use of growth factors. Further plating allows EBs to differentiated into contractile cardiomyocytes.

  20. Communications

    1. Polymers Fight HIV: Potent (Pro)Drugs Identified Through Parallel Automated Synthesis

      Kaja Zuwala, Anton A. A. Smith, Almar Postma, Carlos Guerrero-Sanchez, Pau Ruiz-Sanchis, Jesper Melchjorsen, Martin Tolstrup and Alexander N. Zelikin

      Article first published online: 9 MAY 2014 | DOI: 10.1002/adhm.201400148

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      Macromolecular (pro)drugs interfere with the proliferation of HIV through both inhibition of viral cell entry and via intracellular delivery of antiviral drugs. Lead polymer conjugates exhibit longevity of action exceeding that of parent nucleoside analogue drug and are active in primary T cell over at least 72 h.

  21. Full Papers

    1. Suppression of VEGF by Reversible-PEGylated Histidylated Polylysine in Cancer Therapy

      Xiaojun Cai, Haiyan Zhu, Haiqing Dong, Yongyong Li, Jiansheng Su and Donglu Shi

      Article first published online: 7 MAY 2014 | DOI: 10.1002/adhm.201400063

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      Reversible PEGylation and histidylation of polylysine catiomer critically function to facilitate the efficient delivery of siRNA–VEGF. The unique structural designs significantly affect the gene transfection efficiencies both in vitro and in vivo, and further result in effective inhibition of tumor growth on the murine xenograft models.

  22. Communications

    1. Molecular Etching: A Novel Methodology for the Generation of Complex Micropatterned Growth Surfaces for Human Cellular Assays

      Ayhan Atmanli, Dongjian Hu and Ibrahim J. Domian

      Article first published online: 7 MAY 2014 | DOI: 10.1002/adhm.201400010

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      The extracellular matrix (ECM) is the noncellular component of all tissues. In vitro, micropatterning of ECM has enabled the control of cell shape and function. Here, a novel methodology to reliably micropattern complex, biologically active ECM protein mixtures on a variety of growth substrates is presented. It is further shown that these conditions provide more physiologic cues than single purified proteins.

  23. Full Papers

    1. Gold-Nanorod-Assisted Near-Infrared Stimulation of Primary Auditory Neurons

      Jiawey Yong, Karina Needham, William G. A. Brown, Bryony A. Nayagam, Sally L. McArthur, Aimin Yu and Paul R. Stoddart

      Article first published online: 5 MAY 2014 | DOI: 10.1002/adhm.201400027

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      Primary auditory neurons incubated with silica-coated gold nanorods exhibit enhanced electrical activity when exposed to 780 nm pulsed laser irradiation, as observed by whole-cell patch-clamp electrophysiology. The enhancement appears to be driven by the laser-induced photothermal heating of Au NRs in the vicinity of the neurons.

    2. Graphene-Based Electroresponsive Scaffolds as Polymeric Implants for On-Demand Drug Delivery

      Ania Servant, Veronica Leon, Dhifaf Jasim, Laura Methven, Patricia Limousin, Ester Vazquez Fernandez-Pacheco, Maurizio Prato and Kostas Kostarelos

      Article first published online: 5 MAY 2014 | DOI: 10.1002/adhm.201400016

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      The fabrication of graphene hydrogel hybrid electroactive scaffolds for on-demand drug delivery is shown. In this study, an illustration of how the heat dissipating properties of graphene can provide significant advantages in the design of electroresponsive hydrogels, able to maintain optimal functionality by overcoming adverse effects due to unwanted heating, is offered.

    3. Inflammation-Induced Drug Release by Using a pH-Responsive Gas-Generating Hollow-Microsphere System for the Treatment of Osteomyelitis

      Ming-Fan Chung, Wei-Tso Chia, Hung-Yi Liu, Chun-Wen Hsiao, Hsu-Chan Hsiao, Chih-Man Yang and Hsing-Wen Sung

      Article first published online: 2 MAY 2014 | DOI: 10.1002/adhm.201400158

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      In the inflammation-induced acidic environment of osteomyelitis, the NaHCO3 in the hollow microspheres (HMs) that are embedded in the bone cement will react with the acid to quickly form CO2 bubbles, which create pressure inside the HMs and disrupt their walls, promptly and locally unloading an amount of encapsulated vancomycin that exceeds the therapeutic threshold for curing the disease.

    4. Intracellular Delivery of Peptide Nucleic Acid and Organic Molecules Using Zeolite-L Nanocrystals

      Alessandro Bertucci, Henning Lülf, Dedy Septiadi, Alex Manicardi, Roberto Corradini and Luisa De Cola

      Article first published online: 2 MAY 2014 | DOI: 10.1002/adhm.201400116

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      Multifunctional nanocarriers based on zeolite-L crystals bearing PNA probes are developed for biomedical applications. The surface of the nanoparticles is covalently functionalized with PNA strands able to recognize specific target sequences, whereas the internal channel system is exploited to carry fluorophores or model drug molecules into living cells, to create multifunctional nanosystems for theranostic applications.

    5. A Symmetrical Fluorous Dendron-Cyanine Dye-Conjugated Bimodal Nanoprobe for Quantitative 19F MRI and NIR Fluorescence Bioimaging

      Zhe Wang, Xuyi Yue, Yu Wang, Chunqi Qian, Peng Huang, Marty Lizak, Gang Niu, Fu Wang, Pengfei Rong, Dale O. Kiesewetter, Ying Ma and Xiaoyuan Chen

      Article first published online: 2 MAY 2014 | DOI: 10.1002/adhm.201400088

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      19F MRI and optical imaging are two powerful noninvasive molecular imaging modalities in biomedical applications. A bimodal nanoprobe incorporating a symmetrical fluorous dendron-cyanine dye single molecule is developed by addressing shortcomings of conventional contrast agents to explore the quantitative 19F MRI and fluorescent imaging. This nanoprobe can hold great potential for quantitative and sensitive multi-modal bioimaging.

  24. 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.

  25. 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, Stuart 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.

  26. 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.

  27. 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.

  28. 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.

  29. 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.

  30. 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. You have full text access to this OnlineOpen article
      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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. Communications

    1. You have full text access to this OnlineOpen article
      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.

  36. 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.

  37. 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.

  38. 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.

  39. 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.

  40. 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.

  41. 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.

  42. 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.

  43. 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.

  44. 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.

  45. 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.

  46. 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.

  47. 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.

  48. 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. 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.

  49. 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.

  50. 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.

  51. 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.

  52. 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.

  53. 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.

  54. 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.

  55. 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.

    2. 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.

    3. 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.

    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.

  56. 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.

  57. 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.

  58. Communications

    1. 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.

  59. 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.

  60. 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.

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