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  1. Full Papers

    1. The Effects of Crystal Phase and Particle Morphology of Calcium Phosphates on Proliferation and Differentiation of Human Mesenchymal Stromal Cells

      Charlène Danoux, Daniel Pereira, Nicola Döbelin, Christoph Stähli, Jake Barralet, Clemens van Blitterswijk and Pamela Habibovic

      Version of Record online: 27 MAY 2016 | DOI: 10.1002/adhm.201600184

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      Understanding the relationship between individual properties of crystalline calcium phosphates and a biological response is important for developing effective synthetic bone graft substitutes. The effects of the calcium phosphate crystal phase and particle structure on the behavior of human mesenchymal stromal cells are investigated by precipitating brushite, monetite, and octacalcium phosphate, with brushite and monetite both as needle-shaped and as plate-shaped particles.

    2. You have full text access to this OnlineOpen article
      Harnessing the Versatility of Bacterial Collagen to Improve the Chondrogenic Potential of Porous Collagen Scaffolds

      Paresh A. Parmar, Jean-Philippe St-Pierre, Lesley W. Chow, Jennifer L. Puetzer, Violet Stoichevska, Yong Y. Peng, Jerome A. Werkmeister, John A. M. Ramshaw and Molly M. Stevens

      Version of Record online: 24 MAY 2016 | DOI: 10.1002/adhm.201600136

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      Recombinant bacterial collagens are modified with selected bioactive peptide sequences designed to specifically, dynamically, and noncovalently bind glycosaminoglycans abundantly found in native articular cartilage. The proteins are fabricated into porous foam scaffolds and seeded with human mesenchymal stem cells. Specific functionalized scaffolds lead to extensive chondrogenesis and enhancement of the articular chondrocyte phenotype compared to collagen type I foams.

    3. Controlling Bone Graft Substitute Microstructure to Improve Bone Augmentation

      Zeeshan Sheikh, Justin Drager, Yu Ling Zhang, Mohamed-Nur Abdallah, Faleh Tamimi and Jake Barralet

      Version of Record online: 23 MAY 2016 | DOI: 10.1002/adhm.201600052

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      Onlay block grafting is used frequently for vertical bone augmentation for placing dental implants. In this study, two types of monetite grafts are prepared by wet and dry heating of brushite. The grafts are implanted on rabbit skulls and ≈3.2 mm of bone height gained with wet heat monetite having higher bone volume augmented than their dry heat counterparts.

    4. The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems

      Rosalyn D. Abbott, Rebecca Y. Wang, Michaela R. Reagan, Ying Chen, Francis E. Borowsky, Adam Zieba, Kacey G. Marra, J. Peter Rubin, Irene M. Ghobrial and David L. Kaplan

      Version of Record online: 19 MAY 2016 | DOI: 10.1002/adhm.201600211

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      A silk scaffold system is used to culture liquefied adipose tissues ex vivo. Without the silk scaffold, adipose tissue is too fragile to be cultured from a lipoaspirate sample or as an explant. Soaking silk scaffolds directly from a small volume of lipoaspirate makes this technique amendable to the study of patient-specific disease mechanisms and drug responses.

  2. Reviews

    1. Nano-Enabled Approaches for Stem Cell-Based Cardiac Tissue Engineering

      Mahshid Kharaziha, Adnan Memic, Mohsen Akbari, David A. Brafman and Mehdi Nikkhah

      Version of Record online: 19 MAY 2016 | DOI: 10.1002/adhm.201600088

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      Cardiac diseases are the most prevalent causes of mortality in the world. Cell-based transplanting and tissue engineering have gained significant attention for cardiac therapy. In this article, we explore tissue engineering strategies, which have emphasized on the use of nano-enabled approaches (e.g. nanoparticles, nanotopographies) in combination with stem cells for regeneration and repair of injured myocardium upon myocardial infarction (MI).

  3. Full Papers

    1. Rational Design of Prevascularized Large 3D Tissue Constructs Using Computational Simulations and Biofabrication of Geometrically Controlled Microvessels

      Chiara Arrigoni, Matilde Bongio, Giuseppe Talò, Simone Bersini, Junko Enomoto, Junji Fukuda and Matteo Moretti

      Version of Record online: 18 MAY 2016 | DOI: 10.1002/adhm.201500958

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      Vascularization of thick 3D constructs is a key challenge in tissue engineering. This paper presents a multimodal approach for the generation of prevascularized fibrin hydrogels based on computational simulations of oxygen distribution, biofabrication, and dynamic co-culture systems, highlighting different effects on microvessel outgrowth depending on the combination of shear stress and oxygen concentration.

    2. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release

      Lang Rao, Qian-Fang Meng, Qinqin Huang, Pei Liu, Lin-Lin Bu, Kiran Kumar Kondamareddy, Shi-Shang Guo, Wei Liu and Xing-Zhong Zhao

      Version of Record online: 18 MAY 2016 | DOI: 10.1002/adhm.201600303

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      Biomimetically coated core–shell SiO2@TiO2 nanoparticles with enhanced photocatalytic activity are able to shed their surface erythrocyte membrane coatings by UV-light–triggered degradation of the latter. This approach demonstrates the potential of using biomimetic cell-membrane–coated nanocarriers for controlled drug delivery.

    3. In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization

      Benjamin A. Juliar, Melissa M. Bromley, Alexander Moncion, Denise C. Jones, Eric G. O'Neill, Christopher G. Wilson, Renny T. Franceschi and Mario L. Fabiilli

      Version of Record online: 18 MAY 2016 | DOI: 10.1002/adhm.201600008

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      An ultrasound-based technique called acoustic droplet vaporization (ADV) is used to control the release of a lipoplex—containing plasmid DNA— from a sonosensitive double emulsion. The lipoplex is encapsulated into the emulsion and released by ADV without affecting its bioactivity. Significantly greater transfection is observed following ADV, which demonstrates that ADV could have utility in spatiotemporal control of gene delivery.

  4. Communications

    1. Anisotropically Stiff 3D Micropillar Niche Induces Extraordinary Cell Alignment and Elongation

      Yunus Alapan, Mousa Younesi, Ozan Akkus and Umut A. Gurkan

      Version of Record online: 18 MAY 2016 | DOI: 10.1002/adhm.201600096

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      A microfabricated pillar substrate is developed to confine, align, and elongate cells, allowing decoupled analysis of stiffness and directionality in 3D. Mesenchymal stem cells and cardiomyocytes are successfully confined in a 3D environment with precisely tunable stiffness anisotropy. It is discovered that anisotropically stiff micropillar substrates provide cellular confinement in 3D, aligning cells in the stiffer direction with extraordinary elongation.

    2. Enhanced Lineage-Specific Differentiation Efficiency of Human Induced Pluripotent Stem Cells by Engineering Colony Dimensionality Using Electrospun Scaffolds

      Maricela Maldonado, Gerardo Ico, Karen Low, Rebeccah J. Luu and Jin Nam

      Version of Record online: 17 MAY 2016 | DOI: 10.1002/adhm.201600141

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      Electrospun scaffolds with varied stiffness promote distinct colony morphology of human induced pluripotent stem cells, which affects their subsequent differentiation. On soft scaffolds, induced pluripotent stem cells develop 3D colonies due to the pliability of the electrospun fibrous networks, leading to greater differentiation tendency to ectodermal lineage.

    3. Facile Cell Sheet Harvest and Translocation Mediated by a Thermally Expandable Hydrogel with Controlled Cell Adhesion

      Yu Bin Lee, Young Min Shin, Eun Mi Kim, Jangsoo Lim, Joong-Yup Lee and Heungsoo Shin

      Version of Record online: 17 MAY 2016 | DOI: 10.1002/adhm.201600210

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      Facile cell sheet translocation system is developed based on a thermally expandable hydrogel with modular cell adhesion favorable for both robust cell sheet formation and harvest. Efficient translocation is achieved at moderate cell–substrate interaction, which can be tuned by two-step reactions of mussel-inspired coating.

  5. Full Papers

    1. Investigation of Migration and Differentiation of Human Mesenchymal Stem Cells on Five-Layered Collagenous Electrospun Scaffold Mimicking Native Cartilage Structure

      Jenny W. Reboredo, Tobias Weigel, Andre Steinert, Lars Rackwitz, Maximilian Rudert and Heike Walles

      Version of Record online: 17 MAY 2016 | DOI: 10.1002/adhm.201600134

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      The preparation of a multilayered electrospun scaffold is reported that consists of collagen type I and II and has the potency to induce the differentiation of human mesenchymal stem cells toward the chondrogenic lineage. The novel biomaterial is designed for the replacement of damaged cartilage that allows repopulation by host cells and synthesis of a new natural matrix.

    2. Stimuli-Regulated Enzymatically Degradable Smart Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery

      Hyunwoo Kim, Jinhwan Kim, Minkyung Lee, Hee Cheul Choi and Won Jong Kim

      Version of Record online: 17 MAY 2016 | DOI: 10.1002/adhm.201600246

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      A rationally designed graphene oxide nanocarrier with polyethylene glycol and branched polyethylenimine via disulfide linkage shows photothermally induced endosomal escape and gene release in a reducing intracellular environment. Enzymatic degradation of the nanocarrier in macrophages ensures its effective excretion. This strategy can be further applied in safe carbon-based nanomedicine.

  6. Communications

    1. Subdermal Flexible Solar Cell Arrays for Powering Medical Electronic Implants

      Kwangsun Song, Jung Hyun Han, Taehoon Lim, Namyun Kim, Sungho Shin, Juho Kim, Hyuck Choo, Sungho Jeong, Yong-Chul Kim, Zhong Lin Wang and Jongho Lee

      Version of Record online: 3 MAY 2016 | DOI: 10.1002/adhm.201600222

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      A subdermally implantable flexible photovoltatic (IPV) device is proposed for supplying sustainable electric power to in vivo medical implants. Electric properties of the implanted IPV device are characterized in live animal models. Feasibility of this strategy is demonstrated by operating a flexible pacemaker with the subdermal IPV device which generates DC electric power of ≈647 μW under the skin.

    2. Tissue in Cube: In Vitro 3D Culturing Platform with Hybrid Gel Cubes for Multidirectional Observations

      Masaya Hagiwara, Tomohiro Kawahara and Rina Nobata

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600167

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      An in vitro 3D culturing platform enabling multidirectional observations of 3D biosamples is presented. The 3D structure of biosamples can be recognized without fluorescence. The cubic platform employs two types of hydrogels that are compatible with conventional culture dishes or well plates, facilitating growth in culture, ease of handling, and viewing at multiple angles.

  7. Full Papers

    1. Multifunctional Polymeric Nanosystems for Dual-Targeted Combinatorial Chemo/Antiangiogenesis Therapy of Tumors

      Fatima Zohra Dahmani, Yan Xiao, Juan Zhang, Yao Yu, Jianping Zhou and Jing Yao

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600169

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      A self-assembling nanosystem comprising of LMWH, gambogic acid, and c(RGDyK) peptide is developed for targeted chemo/antiangiogenesis combination therapy. This nanoassembly exhibiting both cytotoxic and antiangiogenic effects along with a dual targeting capability to tumor cells and angiogenic endothelium is shown to substantially improve the therapeutic efficacy of delivered drugs with reduced side-toxicity.

    2. Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering

      Amy Gelmi, Artur Cieslar-Pobuda, Ebo de Muinck, Marek Los, Mehrdad Rafat and Edwin W. H. Jager

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600307

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      Here a new type of smart cardiac patch material, the electromechanically active fiber scaffold, is presented. The scaffold is capable of delivering electrical and mechanical stimulation to individual cells and demonstrates controlled volume change actuation. The scaffold is noncytotoxic and may enhance the cardiac differentiation of human induced pluripotent stem cells.

    3. Surface-Driven Collagen Self-Assembly Affects Early Osteogenic Stem Cell Signaling

      Tojo Razafiarison, Unai Silván, Daniela Meier and Jess G. Snedeker

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600128

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      The role of supramolecular ligand assembly on silicone substrates as a potential significant regulator of human bone marrow stromal cell adhesion and differentiation is investigated. A smooth collagen topography obtained on hydrophilic silicone tends to accelerate the onset of osteogenic differentiation when compared to the rough collagen layer on pristine hydrophobic silicone.

    4. Flexible Inkjet-Printed Multielectrode Arrays for Neuromuscular Cartography

      Timothée Roberts, Jozina B. De Graaf, Caroline Nicol, Thierry Hervé, Michel Fiocchi and Sébastien Sanaur

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600108

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      Inkjet printed flexible PEDOT:PSS multielectrode arrays (MEAs) mapping the neuromuscular activity of an upper arm are reported. The device is validated by Electrochemical Impedance Spectroscopy, electrocardiographic and electromyographic recordings. Such results provide a new opportunity to control the movement of prosthesis with such MEAs.

  8. Communications

    1. Mimicking Tissue Boundaries by Sharp Multiparameter Matrix Interfaces

      Jiranuwat Sapudom, Stefan Rubner, Steve Martin and Tilo Pompe

      Version of Record online: 29 APR 2016 | DOI: 10.1002/adhm.201600295

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      Engineering interfaces of distinct extracellular compartments mimicking native tissues are key for in-depth in vitro studies on developmental and disease processes in biology and medicine. Sharp interfaces of extracellular matrices are constructed based on fibrillar collagen I networks with a multiparameter control of topology, mechanics, and composition, and their distinct impact on triggering the directionality of cancer cell migration is demonstrated.

  9. Full Papers

    1. A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays

      Xiao Li and Xinyu Liu

      Version of Record online: 28 APR 2016 | DOI: 10.1002/adhm.201501038

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      The first microfluidic paper-based origami nanobiosensor, featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, is developed for label-free, ultrasensitive immunoassays. The sensor is able to achieve a limit of detection as low as 300 fg mL−1 for HIV p24 antigen in human serum.

  10. Reviews

    1. Viruses, Artificial Viruses and Virus-Based Structures for Biomedical Applications

      Patrick van Rijn and Romana Schirhagl

      Version of Record online: 27 APR 2016 | DOI: 10.1002/adhm.201501000

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      Virus particles have unique properties including a reproducible and controllable nanostructure, as well as their ability to deliver their genetic cargo. Thus they have inspired scientists to engineer them artificially. This review covers the latest advances in this field and the use of artificial virus structures for biomedical applications.

  11. Full Papers

    1. High-Throughput Blood- and Lymph-Capillaries with Open-Ended Pores Which Allow the Transport of Drugs and Cells

      Daichi Hikimoto, Akihiro Nishiguchi, Michiya Matsusaki and Mitsuru Akashi

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600180

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      Perfusable blood- and lymph-capillary (BC/LC) networks embedded in 3D-tissues inside a 24-microplate using a cell-coating technology are demonstrated which allow location control of cell layers. The constructed BC networks are able to mimick in vivo processes like cancer metastasis, extravasation, growth, and growth suppression by drug treatment. These BC/LC networks with open pores are useful as a high-throughput 3D-tissue in pharmaceutical and tissue engineering fields.

    2. An In Situ Gelling Drug Delivery System for Improved Recovery after Spinal Cord Injury

      Dongfei Liu, Tao Jiang, Weihua Cai, Jian Chen, Hongbo Zhang, Sami Hietala, Hélder A. Santos, Guoyong Yin and Jin Fan

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600055

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      An in situ gelling drug delivery system is developed for spinal cord injury therapy. The administration of drug-incorporated hydrogel inhibits the apoptotic cell death and glial scar formation, enhances the neuron regeneration, provides neuroprotection to the injured spinal cord, and ultimately improves the locomotor recovery in rats.

    3. Hybrid Polycaprolactone/Alginate Scaffolds Functionalized with VEGF to Promote de Novo Vessel Formation for the Transplantation of Islets of Langerhans

      Giulia Marchioli, Andrea Di Luca, Eelco de Koning, Marten Engelse, Clemens A. Van Blitterswijk, Marcel Karperien, Aart A. Van Apeldoorn and Lorenzo Moroni

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600058

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      A hybrid scaffold for embedding the islets of Langerhans to achieve enhanced revascularization upon transplantation is presented. Islets are secured in the central alginate core, while the outer polycaprolactone ring is functionalized with vascular endothelial growth factor. These constructs provide protection for islets and facilitate blood vessel ingrowth in proximity to the embedded tissue.

    4. Osteoanabolic Implant Materials for Orthopedic Treatment

      Yun-Fei Ding, Rachel W. Li, Masaaki Nakai, Trina Majumdar, Dong-Hai Zhang, Mitsuo Niinomi, Nick Birbilis, Paul N. Smith and Xiao-Bo Chen

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600074

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      An orthopedic implant material specifically designed for osteoporotic bone fractures is reported herein. A strontium phosphate (SrPO4) coating applied to a bone-mimicking low elastic modulus Ti alloy, TNTZ, results in upregulating the growth of osteoblasts and downregulating that of osteoclasts. This functional SrPO4 coating provides a new direction in the design and manufacture of implantable devices used in the treatment of osteoporotic bone fractures.

    5. Far-Red Fluorescent Lipid-Polymer Probes for an Efficient Labeling of Enveloped Viruses

      William Lacour, Salim Adjili, Julie Blaising, Arnaud Favier, Karine Monier, Sarra Mezhoud, Catherine Ladavière, Christophe Place, Eve-Isabelle Pécheur and Marie-Thérèse Charreyre

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600091

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      Far-red emitting fluorescent lipid probes are desirable to label enveloped viruses and to track them by optical microscopy inside autofluorescent cells. Water-soluble lipid-polymer probes harboring hydrophilic or hydrophobic far-red dyes are synthesized and used to efficiently label Hepatitis C Virus. Labeled viral particles can be successfully tracked inside hepatocarcinoma cells in spite of their autofluorescence up to 700 nm.

  12. Communications

    1. Surface-Mediated Stimuli Responsive Delivery of Organic Molecules from Porous Carriers to Adhered Cells

      Bahar Ergün, Luisa De Cola, Hans-Joachim Galla and Nermin Seda Kehr

      Version of Record online: 26 APR 2016 | DOI: 10.1002/adhm.201600098

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      The alternating layer-by-layer deposition of oppositely charged polyelectrolytes on fluorescence-dye-(Hst)-loaded zeolites L (HstZeo-PSS/PLL) is described. The arrays and nanocomposite (NC) hydrogels of HstZeo-PSS/PLL are prepared. The subsequent cell experiments show the potential application of arrays and NC hydrogels of HstZeo-PSS/PLL as alternative 2D- and 3D-surfaces, respectively, for 2D- and 3D-surface-mediated controlled organic molecules delivery applications.

    2. Photoactive g-C3N4 Nanosheets for Light-Induced Suppression of Alzheimer's β-Amyloid Aggregation and Toxicity

      You Jung Chung, Byung Il Lee, Jong Wan Ko and Chan Beum Park

      Version of Record online: 25 APR 2016 | DOI: 10.1002/adhm.201500964

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      Graphitic carbon nitride (g-C3N4) has a suppressive capability toward Alzheimer's Aβ aggregation under light-illumination. Photoinduced electrons of g-C3N4 generate reactive oxygen resulting in photooxidation of amyloid peptides that blocks Aβ aggregation. Fe doping of g-C3N4 frameworks results in enhanced optical properties and even stronger inhibition of Aβ aggregation.

    3. Developing Precisely Defined Drug-Loaded Nanoparticles by Ring-Opening Polymerization of a Paclitaxel Prodrug

      Jinyao Liu, Yan Pang, Jayanta Bhattacharyya, Wenge Liu, Isaac Weitzhandler, Xinghai Li and Ashutosh Chilkoti

      Version of Record online: 25 APR 2016 | DOI: 10.1002/adhm.201600230

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      Nanoparticles with high paclitaxel (PTX) loading and low systemic toxicity are prepared in scalable and versatile manner via one-step ring-opening polymerization of a prodrug monomer consisting of PTX that is appended to a cyclic carbonate through a hydrolysable ester linker. Initiating this monomer from a hydrophilic macroinitiator results in an amphiphilic diblock copolymer that spontaneously self-assembles into well-defined nanoparticles with tunable size.

  13. Full Papers

    1. Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity

      Basmah A. Othman, Christina Greenwood, Ayman F. Abuelela, Anil A. Bharath, Shu Chen, Ioannis Theodorou, Trevor Douglas, Maskai Uchida, Mary Ryan, Jasmeen S. Merzaban and Alexandra E. Porter

      Version of Record online: 25 APR 2016 | DOI: 10.1002/adhm.201501012

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      A fluorescently labeled RGD-targeted ZnO nanoparticle (ZnO-GFP-HCV-RGD NP) is developed for targeted delivery of ZnO to integrin αvβ3 receptors expressed on triple negative breast cancer cells (TNBCs). Correlative light-electron microscopy shows ZnO-GFP-HCV-RGD NPs dissolve in the intracellular environment of TNBCs and cause apoptosis with intratumor heterogeneity. More importantly, these NPs provide a possible strategy for targeted breast cancer therapy.

    2. Development and Characterization of Organic Electronic Scaffolds for Bone Tissue Engineering

      Donata Iandolo, Akhilandeshwari Ravichandran, Xianjie Liu, Feng Wen, Jerry K. Y. Chan, Magnus Berggren, Swee-Hin Teoh and Daniel T. Simon

      Version of Record online: 25 APR 2016 | DOI: 10.1002/adhm.201500874

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      PEDOT-coated 3D macroporous scaffolds are developed as active substrates for mesenchymal stem cell culture. The conducting polymer PEDOT:tosylate is deposited on medical-grade polycaprolactone scaffolds via vapor phase polymerization. This results in a continuous conformal layer, and electrically and electrochemically active scaffolds. The mechanical strength of the functionalized scaffolds can be preserved, and they are shown to promote stem cell proliferation.

    3. Micropatterning Facilitates the Long-Term Growth and Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks

      Lena F. Burbulla, Kristin G. Beaumont, Milan Mrksich and Dimitri Krainc

      Version of Record online: 24 APR 2016 | DOI: 10.1002/adhm.201500900

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      While conventional methods for long-term culturing of induced pluripotent stem cell (iPSC)-derived neuronal cells result in clustering of neurons, micropatterned surfaces enable culturing of individual neurons and defined neuronal networks to monitor cellular processes such as neurite outgrowth and trafficking of neuronal organelles over extended periods of time.

    4. Mechanocompatible Polymer-Extracellular-Matrix Composites for Vascular Tissue Engineering

      Bin Jiang, Rachel Suen, Jiao-Jing Wang, Zheng J. Zhang, Jason A. Wertheim and Guillermo A. Ameer

      Version of Record online: 24 APR 2016 | DOI: 10.1002/adhm.201501003

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      Heparinized mechanocompatible polymer-extracellular-matrix (ECM) composites for vascular tissue engineering are fabricated by reacting heparin-(N-[ß-maleimidopropionic acid] hydrazide) with thiolated polymer-ECM composites via “click” chemistry. This mechanocompatible strategy improves ECM hemocompatibility without affecting its mechanical properties. Mechanocompatible polymer-ECM composites outperform heparinized ECM vascular grafts prepared using carbodiimide chemistry in vivo, highlighting the importance of maintaining the original ECM mechanical properties.

    5. Near-Infrared-Light-Assisted Photothermal Polymerization for Transdermal Hydrogelation and Cell Delivery

      Hwangjae Lee, Solchan Chung, Min-Gon Kim, Luke P. Lee and Jae Young Lee

      Version of Record online: 24 APR 2016 | DOI: 10.1002/adhm.201600048

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      Near infrared-light-assisted photothermal polymerization of diacrylated polyethylene glycol for transdermal hydrogelation is developed and its capacity for cell delivery and encapsulation is examined. NAPP is shown to result in successful transdermal gelation and good viability of the transplanted cells.

    6. Targeted siRNA Delivery Using a Lipo-Oligoaminoamide Nanocore with an Influenza Peptide and Transferrin Shell

      Wei Zhang, Katharina Müller, Eva Kessel, Sören Reinhard, Dongsheng He, Philipp M. Klein, Miriam Höhn, Wolfgang Rödl, Susanne Kempter and Ernst Wagner

      Version of Record online: 24 APR 2016 | DOI: 10.1002/adhm.201600057

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      A multifunctional transferrin-receptor-(TfR)-targeted small interfering RNA (siRNA) delivery system is developed based on cationic siRNA complexes formed with precise sequence-defined T-shaped lipo-oligomer, sequentially decorated with PEG-linked transferrin-(Tf)-targeting ligand for surface shielding and specific cellular uptake through TfR, and with INF7 as small pH-triggered peptide for endosomal escape.

    7. Tuning Cell Differentiation into a 3D Scaffold Presenting a Pore Shape Gradient for Osteochondral Regeneration

      Andrea Di Luca, Ivan Lorenzo-Moldero, Carlos Mota, Antonio Lepedda, Dietmar Auhl, Clemens Van Blitterswijk and Lorenzo Moroni

      Version of Record online: 24 APR 2016 | DOI: 10.1002/adhm.201600083

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      Additive manufacturing is used to fabricate 3D scaffolds displaying gradients in pore shape. Studies of adult stem cell activity show that by changing pore shapes from cubical to rhomboidal, cells increasingly shift from a more chondrogenic to a more osteogenic differentiated phenotype in the presence of soluble factors. This may contribute to enhance osteochondral regeneration in orthopedic treatments.

  14. Communications

    1. Self-Assembly Protein Nanogels for Safer Cancer Immunotherapy

      Alberto Purwada, Ye F. Tian, Weishan Huang, Kathleen M. Rohrbach, Simrita Deol, Avery August and Ankur Singh

      Version of Record online: 21 APR 2016 | DOI: 10.1002/adhm.201501062

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      Soluble antigen-based cancer vaccines have poor retention in tissues along with suboptimal antigen processing by dendritic cells. Multiple booster doses are often needed, leading to dose limiting systemic toxicity. A versatile, immunomodulatory, self-assembly protein nanogel vaccine is reported that induces robust immune cell response at lower antigen doses than soluble antigens, an important step towards biomaterials-based safer immunotherapy approaches.

  15. Full Papers

    1. Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering

      Daniela Filipa Duarte Campos, Andreas Blaeser, Kate Buellesbach, Kshama Shree Sen, Weiwei Xun, Walter Tillmann and Horst Fischer

      Version of Record online: 13 APR 2016 | DOI: 10.1002/adhm.201501033

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      Adequate printability characteristics of polysaccharide hydrogels can be combined with biological agents present in collagen hydrogels to achieve both defined 3D-printed constructs with satisfactory conditions for mesenchymal stem cell growth and osteogenic differentiation. By adjusting the ratio of collagen type I in hydrogel blends, it is possible to fine-tune the osteogenesis of MSC in such matrices that are additionally suitable for 3D-bioprinting.

    2. Bioactive Anti-Thrombotic Modification of Decellularized Matrix for Vascular Applications

      Jeremy J. Glynn and Monica T. Hinds

      Version of Record online: 13 APR 2016 | DOI: 10.1002/adhm.201600020

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      The decellularized biomaterial derived from porcine small intestinal submucosa (SIS) is widely used in tissue repair, but can cause blood clot formation. An endothelial-inspired, biologically active coating consisting of thrombomodulin and heparin inhibits blood coagulation and reduces blood clot formation on SIS when exposed to flowing whole blood in an extracorporeal blood loop, as shown.

    3. Enhancing the Biomechanical Performance of Anisotropic Nanofibrous Scaffolds in Tendon Tissue Engineering: Reinforcement with Cellulose Nanocrystals

      Rui M. A. Domingues, Silvia Chiera, Pavel Gershovich, Antonella Motta, Rui L. Reis and Manuela E. Gomes

      Version of Record online: 5 APR 2016 | DOI: 10.1002/adhm.201501048

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      Cellulose nanocrystals (CNCs) are applied as bioderived reinforcing nanofillers in anisotropically aligned electrospun scaffolds for tendon/ligament tissue engineering (TE). The incorporation of small amounts of CNCs into tendon mimetic scaffolds has a significant biomaterial-toughening effect without negatively affecting biological performance. The strategy enables to exploit the benefits of the scaffolds topography and hierarchy in high mechanically demanding tendon/ligament TE.

  16. Communications

    1. Efficient Purification and Release of Circulating Tumor Cells by Synergistic Effect of Biomarker and SiO2@Gel-Microbead-Based Size Difference Amplification

      Qinqin Huang, Bo Cai, Bolei Chen, Lang Rao, Zhaobo He, Rongxiang He, Feng Guo, Libo Zhao, Kiran Kumar Kondamareddy, Wei Liu, Shishang Guo and Xing-Zhong Zhao

      Version of Record online: 29 MAR 2016 | DOI: 10.1002/adhm.201500981

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      Microfluidics-based circulating tumor cell (CTC) isolation is achieved by using gelatin-coated silica microbeads conjugated to CTC-specific antibodies. Bead-binding selectively enlarges target cell size, providing efficient high-purity capture. CTCs captured can be further released non-invasively. This stratagem enables high-performance CTC isolation for subsequent studies.

  17. Full Papers

    1. Functional 3D Neural Mini-Tissues from Printed Gel-Based Bioink and Human Neural Stem Cells

      Qi Gu, Eva Tomaskovic-Crook, Rodrigo Lozano, Yu Chen, Robert M. Kapsa, Qi Zhou, Gordon G. Wallace and Jeremy M. Crook

      Version of Record online: 29 MAR 2016 | DOI: 10.1002/adhm.201600095

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      Three dimensional (3D) human neural tissue is generated by bioprinting human neural stem cells with a novel polysaccharide-based bioink. After bioink gelation, encapsulated stem cells self-renew and differentiate to neuronal and neuroglial cell lineage. Neurons are predominantly gamma-aminobutyric acid expressing, establish networks, are spontaneously active, and show a bicuculline-induced increased calcium response.

  18. Progress Reports

    1. Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

      Karen M. Oprych, Raymond L. D. Whitby, Sergey V. Mikhalovsky, Paul Tomlins and Jimi Adu

      Version of Record online: 29 MAR 2016 | DOI: 10.1002/adhm.201500864

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      Carbon nanotubes (CNTs) are a unique nanomaterial currently being developed for engineering and interfacing with neurological tissues. In the context of the “state-of-the-art” in peripheral nerve repair, this progress report will consolidate and evaluate the current literature pertinent to CNTs as a biomaterial for supporting axon regeneration and outlines how CNTs may enhance the performance of next generation peripheral nerve repair conduits.

  19. Full Papers

    1. Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for Targeting Bacteria Residing inside Immune Cells

      Chuan Yang, Sangeetha Krishnamurthy, Jie Liu, Shaoqiong Liu, Xiaohua Lu, Daniel J. Coady, Wei Cheng, Gennaro De Libero, Amit Singhal, James L. Hedrick and Yi Yan Yang

      Version of Record online: 29 MAR 2016 | DOI: 10.1002/adhm.201600070

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      Antibacterial star polycarbonates containing mannose groups are synthesized. The mannose-functionalized polymer of optimized composition demonstrates mannose receptor-mediated intracellular activity against BCG mycobacteria without inducing cytotoxicity or hemolysis at the effective dose. It thus has potential as an antibacterial agent in treating infectious diseases caused by intracellular bacteria such as tuberculosis.

    2. A Closed Chondromimetic Environment within Magnetic-Responsive Liquified Capsules Encapsulating Stem Cells and Collagen II/TGF-β3 Microparticles

      Clara R. Correia, Sara Gil, Rui L. Reis and João F. Mano

      Version of Record online: 18 MAR 2016 | DOI: 10.1002/adhm.201600034

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      Multilayered and liquified magnetic capsules encapsulating microparticles and stem cells are proposed as an injectable and self-regulated system to regenerate cartilage. The microparticle's surface is modified with TGF-β3 cross-linked to collagen II. Within the closed 3D chondromimetic environment, encapsulated stem cells are expected to differentiate toward the chondrogenic lineage and maintain their phenotype without growth factor supplementation.

    3. Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents

      Adem Yildirim, Rajarshi Chattaraj, Nicholas T. Blum, Galen M. Goldscheitter and Andrew P. Goodwin

      Version of Record online: 15 MAR 2016 | DOI: 10.1002/adhm.201600030

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      A fluorocarbon-free nanoscale ultrasound contrast agent is described based on mesoporous silica particles with hydrophobic interiors and resuspension in an amphiphilic copolymer. Administration of high intensity focused ultrasound (HIFU) produces macroscopic bubbles, in the presence of down to 1010 nanoparticles particles mL−1. These agents provide ultrasound contrast in biological media, and imaging was sustained continuously for at least 20 min.

    4. Phase and Size Control of Core–Shell Upconversion Nanocrystals Light up Deep Dual Luminescence Imaging and CT In Vivo

      Ning Kang, Yu Liu, Yaming Zhou, Dong Wang, Chuan Chen, Shefang Ye, Liming Nie and Lei Ren

      Version of Record online: 15 MAR 2016 | DOI: 10.1002/adhm.201600159

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      The crystalline phase and size of NaLuF4 - based Upconversion Nanocrystals is successfully controlled by a novel strategy using yttrium ion doping. Superior performance of the crystals is demonstrated in both, deep luminscence imaging and computer tomography.

  20. Communications

    1. Carbon-Quantum-Dots-Loaded Mesoporous Silica Nanocarriers with pH-Switchable Zwitterionic Surface and Enzyme-Responsive Pore-Cap for Targeted Imaging and Drug Delivery to Tumor

      Zhongning Liu, Xin Chen, Xiaojin Zhang, John Justin Gooding and Yongsheng Zhou

      Version of Record online: 14 MAR 2016 | DOI: 10.1002/adhm.201600002

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      Mesoporous silica nanocarriers with pH-switchable antifouling zwitterionic surface, enzyme responsive drug release properties and blue fluorescence are reported. Prolonged circulation in the blood system with zero premature release as well as efficient cellular uptake and intracellular drug release in tumor tissue are achieved.

  21. Full Papers

    1. Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications

      Michael Zakrewsky, Amrita Banerjee, Sanjana Apte, Theresa L. Kern, Mattie R. Jones, Rico E. Del Sesto, Andrew T. Koppisch, David T. Fox and Samir Mitragotri

      Version of Record online: 9 MAR 2016 | DOI: 10.1002/adhm.201600086

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      A unique formulation of choline, geranate, and geranic acid eutectic solvent (CAGE) holds promise as a transformative platform for the prevention and treatment of microbial infections.

    2. Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α

      Wenjie Zhang, Qing Chang, Ling Xu, Guanglong Li, Guangzheng Yang, Xun Ding, Xiansong Wang, Daxiang Cui and Xinquan Jiang

      Version of Record online: 4 MAR 2016 | DOI: 10.1002/adhm.201500824

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      Aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. By activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins.


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