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  1. 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

      Article first published 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

      Article first published 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.

  2. 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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.

  3. Communications

    1. Mimicking Tissue Boundaries by Sharp Multiparameter Matrix Interfaces

      Jiranuwat Sapudom, Stefan Rubner, Steve Martin and Tilo Pompe

      Article first published 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.

  4. Full Papers

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

      Xiao Li and Xinyu Liu

      Article first published 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.

  5. Reviews

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

      Patrick van Rijn and Romana Schirhagl

      Article first published 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.

  6. 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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.

  7. 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

      Article first published 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

      Article first published 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

      Article first published 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.

  8. 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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

      Article first published 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.

  9. 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

      Article first published 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.

  10. Reviews

    1. Biodegradable Metals for Cardiovascular Stents: from Clinical Concerns to Recent Zn-Alloys

      Patrick K. Bowen, Emily R. Shearier, Shan Zhao, Roger J. Guillory II, Feng Zhao, Jeremy Goldman and Jaroslaw W. Drelich

      Article first published online: 20 APR 2016 | DOI: 10.1002/adhm.201501019

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      The current belief is that biodegradable stents will drastically reduce, if not eradicate, all of the long-term health risks associated with bare metal stents and drug eluting stents. This review compares bioabsorbable materials and summarizes progress towards bioabsorbable stents. It emphasizes on current understanding of physiological and biological benefits of zinc and its biocompatibility.

  11. 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

      Article first published 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

      Article first published 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.

  12. Communications

    1. A Janus Mucoadhesive and Omniphobic Device for Gastrointestinal Retention

      Young-Ah Lucy Lee, Shiyi Zhang, Jiaqi Lin, Robert Langer and Giovanni Traverso

      Article first published online: 6 APR 2016 | DOI: 10.1002/adhm.201501036

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      A novel Janus device with omniphobic and mucoadhesive sides that exhibit the unique capacity for antifouling and extended gastrointestinal retention is fabricated. This system enables repulsion of the food and fluid stream by the luminal-facing omniphobic side and allows attachment to the gastrointestinal mucosa by the mucoadhesive side.

  13. Full Papers

    1. 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

      Article first published 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.

    2. Guided Homing of Cells in Multi-photon Microfabricated Bioscaffolds

      Mark A. Skylar-Scott, Man-Chi Liu, Yuelong Wu, Atray Dixit and Mehmet Fatih Yanik

      Article first published online: 5 APR 2016 | DOI: 10.1002/adhm.201600082

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      The ability to multi-photon crosslink collagen scaffolds enables the precise fabrication of microvasculature at a resolution close to capillaries. When scaffold microfabrication is coupled with rapid 3D micropatterning of protein cues, this study demonstrates complex microchannels capable of selectively capturing perfused HL-60 leukemia cells.

    3. Highly Selective Photothermal Therapy by a Phenoxylated-Dextran-Functionalized Smart Carbon Nanotube Platform

      Seungmin Han, Taeyun Kwon, Jo-Eun Um, Seungjoo Haam and Woo-Jae Kim

      Article first published online: 31 MAR 2016 | DOI: 10.1002/adhm.201600015

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      A smart targeting photothermal therapy platform, based on phenoxylated-dextran-functionalized single-walled carbon nanotubes (SWNTs), is developed for treatment of inflammatory disease. Phenoxylated dextran efficiently suspends SWNTs by noncovalent π–π stacking and maintains original optical properties of SWNTs. This biocompatible nanoplatform is able to selectively target inflammatory cells over normal cells through the dextran-scavenger-receptor binding process, and induces efficient photothermal ablation of inflammatory macrophages.

  14. 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

      Article first published 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.

  15. Full Papers

    1. Mesoporous Silica Particles as a Multifunctional Delivery System for Pain Relief in Experimental Neuropathy

      Junran Xie, Dongju Xiao, Jinning Zhao, Nianqiang Hu, Qi Bao, Li Jiang and Lina Yu

      Article first published online: 29 MAR 2016 | DOI: 10.1002/adhm.201500996

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      A multifunctional drug delivery system using mesoporous silica nanoparticles that are loaded with Δ9-THC (Δ9-tetrahydrocannabinol) and ARA290 (an erythropoietin-derived polypeptide) is designed. This system attenuates in vitro and in vivo inflammation in an experimental neuropathic animal model, and achieves a sustained relief of injured animals from neuropathic pain induced by both thermal hyperalgesia and mechanical allodynia.

    2. 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

      Article first published 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.

  16. 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

      Article first published 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.

  17. 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

      Article first published 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. Pigmented Silk Nanofibrous Composite for Skeletal Muscle Tissue Engineering

      Shivaprasad Manchineella, Greeshma Thrivikraman, Khadija K. Khanum, Praveen C. Ramamurthy, Bikramjit Basu and T. Govindaraju

      Article first published online: 22 MAR 2016 | DOI: 10.1002/adhm.201501066

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      Electroactive and antioxidant scaffolds are fabricated from silk/melanin composite. These electrospun nanofibrous scaffolds promote myoblast assembly and differentiation into uniformly aligned high aspect ratio myotubes (myogenesis). The potential application of silk/melanin composite mats as electoractive platform for skeletal muscle tissue engineering is demonstrated.

    3. 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

      Article first published 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.

    4. Nanoparticle Targeting of Neutrophils for Improved Cancer Immunotherapy

      Dafeng Chu, Qi Zhao, Jian Yu, Faya Zhang, Hui Zhang and Zhenjia Wang

      Article first published online: 17 MAR 2016 | DOI: 10.1002/adhm.201500998

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      Tumor targeted delivery of therapeutic albumin NPs is mediated by neutrophil recruitment in tumor sites after administration of TA99 monoclonal antibody, resulting in the improved cancer therapy. The studies reveal a new strategy for hijacking of immune systems to deliver therapeutic NPs into the tumor microenvironment.

    5. A Biodesigned Nanocomposite Biomaterial for Auricular Cartilage Reconstruction

      Leila Nayyer, Gavin Jell, Ali Esmaeili, Martin Birchall and Alexander M. Seifalian

      Article first published online: 16 MAR 2016 | DOI: 10.1002/adhm.201500968

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      A porous nanocomposite (POSS-PCU) ear scaffold was developed, which promoted desirable cell interactions in vitro (cell attachment and growth). In vivo, the scaffolds with a similar elastic moduli to native ear cartilage, reduced fibrotic membrane encapsulation compared to the more rigid commercially available implants of similar porosity. These new scaffolds for ear replacement will reduce the high failure rates of existing materials.

    6. Diamond-Nanoneedle-Array-Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology

      Xiaoyue Zhu, Muk Fung Yuen, Li Yan, Zhenyu Zhang, Fujin Ai, Yang Yang, Peter K. N. Yu, Guangyu Zhu, Wenjun Zhang and Xianfeng Chen

      Article first published online: 15 MAR 2016 | DOI: 10.1002/adhm.201500990

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      Diamond nanoneedle arrays can efficiently deliver different biomolecules into living cells by negotiating the cytoplasma barrier. The kinetics of the cell membrance recovery and the potential influence of the diamond nanoneedle treatment on the cell physiology have been systematically investigated.

    7. 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

      Article first published 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.

    8. 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

      Article first published 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.

    9. Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment

      Ana Espinosa, Amanda K. A. Silva, Ana Sánchez-Iglesias, Marek Grzelczak, Christine Péchoux, Karine Desboeufs, Luis M. Liz-Marzán and Claire Wilhelm

      Article first published online: 15 MAR 2016 | DOI: 10.1002/adhm.201501035

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      Heat-generating efficiency of plasmonic nanoparticles is monitored in situ in environments of increasing biological complexity, from aqueous dispersion to cancer cells in vitro and solid tumors in vivo. Thanks to a subset of gold nanostars ranging from 25 to 150 nm, and investigated at three laser excitation wavelengths, the impact of cancer cells internalization on the thermal plasmonic signature is demonstrated.

    10. Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy

      Xiupeng Wang, Xia Li, Kazuko Yoshiyuki, Yohei Watanabe, Yu Sogo, Tadao Ohno, Noriko M. Tsuji and Atsuo Ito

      Article first published online: 14 MAR 2016 | DOI: 10.1002/adhm.201501013

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      A plain mesoporous silica (MS) nanoparticle without any immunomodulatory mole­cules enhances anticancer immunity in vivo. The plain MS nanoparticle promotes both Th1 and Th2 immune responses, enhances the effector memory CD4+ and CD8+ T cell populations in three most important immune organs (bone marrow, lymph node, and spleen).

  18. 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

      Article first published 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.

  19. Full Papers

    1. The Synergistic Effects of Matrix Stiffness and Composition on the Response of Chondroprogenitor Cells in a 3D Precondensation Microenvironment

      Bita Carrion, Mohammad F. Souzanchi, Victor T. Wang, Gopinath Tiruchinapally, Ariella Shikanov, Andrew J. Putnam and Rhima M. Coleman

      Article first published online: 9 MAR 2016 | DOI: 10.1002/adhm.201501017

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      A 3D biosynthetic hydrogel model containing condensation specific proteins is developed. In this system, matrix stiffness and composition can be independently studied. Chondroprogenitor cells encapsulated in hydrogels undergo condensation and subsequent differentiation. In addition to tethering proteins, the mechanical properties of the hydrogels are tuned to investigate the effects of matrix stiffness on the response of chondroprogenitor cells undergoing chondrogenesis.

    2. 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

      Article first published 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.

  20. Communications

    1. A Textile-Based Stretchable Multi-Ion Potentiometric Sensor

      Marc Parrilla, Rocío Cánovas, Itthipon Jeerapan, Francisco J. Andrade and Joseph Wang

      Article first published online: 9 MAR 2016 | DOI: 10.1002/adhm.201600092

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      A textile-based wearable multi-ion potentiometric sensor array is described. The printed flexible sensors operate favorably under extreme mechanical strains (that reflect daily activity) while offering attractive real-time noninvasive monitoring of electrolytes such as sodium and potassium.

  21. Full Papers

    1. Three-Dimensional Graphene: A Biocompatible and Biodegradable Scaffold with Enhanced Oxygenation

      Manuela Loeblein, Guillaume Perry, Siu Hon Tsang, Wenjin Xiao, Dominique Collard, Philippe Coquet, Yasuyuki Sakai and Edwin Hang Tong Teo

      Article first published online: 4 MAR 2016 | DOI: 10.1002/adhm.201501026

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      Biocompatibility and biodegradation of three-dimensional graphene (3D-C) are studied to investigate if it is an adequate scaffold for tissue engineering. The metabolic activities of liver cells (HepG2) on 3D-C show that cell growth has high cell viability and higher oxygenation than on other forms of carbon. 3D-C is also biodegradable via a two-step oxidative biodegradation process and the speed of the biodegradation can be tuned with pretreatment of oxygen plasma.

    2. Destruction of Opportunistic Pathogens via Polymer Nanoparticle-Mediated Release of Plant-Based Antimicrobial Payloads

      Dahlia N. Amato, Douglas V. Amato, Olga V. Mavrodi, Dwaine A. Braasch, Susan E. Walley, Jessica R. Douglas, Dmitri V. Mavrodi and Derek L. Patton

      Article first published online: 4 MAR 2016 | DOI: 10.1002/adhm.201500974

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      Polythioether nanoparticles carrying high capacity plant-based antimicrobial payloads are synthesized via a one-pot, solvent-free thiol-ene photopolymerization in miniemulsion. These nanoparticles function as reservoirs for slow release of thymol and carvacrol into the aqueous phase, and exhibit high efficacy (>99.9% kill efficiency at 24 h) against gram-positive and gram-negative bacteria, including pathogenic species Escherichia coli O157:H7, Staphylococcus aureus, and Burkholderia cenocepacia.

    3. 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

      Article first published 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.

  22. Communications

    1. Photolytic Protein Aggregates: Versatile Materials for Controlled Release of Active Proteins

      Akira Ishiwatari, Satoshi Yamaguchi, Satoshi Takamori, Shinya Yamahira, Kosuke Minamihata and Teruyuki Nagamune

      Article first published online: 4 MAR 2016 | DOI: 10.1002/adhm.201500957

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      Photolytic protein aggregates are developed as a facile and versatile platform for light-induced release of active proteins. The proteins modified with biotin through a photo-cleavable linker rapidly form aggregates with streptavidin and biotinylated functional molecules simply by mixing. Light irradiation releases active proteins from the aggregates in high yields, and light-induced uptake of drug-modified transferrin into living cells is successfully demonstrated.

  23. Full Papers

    1. Programming Mechanical and Physicochemical Properties of 3D Hydrogel Cellular Microcultures via Direct Ink Writing

      Joselle M. McCracken, Adina Badea, Mikhail E. Kandel, A. Sydney Gladman, David J. Wetzel, Gabriel Popescu, Jennifer A. Lewis and Ralph G. Nuzzo

      Article first published online: 29 FEB 2016 | DOI: 10.1002/adhm.201500888

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      Poly-l-lysine (PLL) is an adhesion promotive molecule absorbed by 3D-printed microscaffolds that confers robust biocompliance to scaffold hydrogels such as poly(HEMA) that otherwise do not facilitate robust cellular growth. Subtle differences in poly(HEMA) hydrogel mesh properties impact PLL absorption kinetics, which controls growth compliance of poly(HEMA) films upon seeding them with NIH/3T3 or MC3T3-E1 cell lines.

    2. Angiogenesis in Liquid Tumors: An In Vitro Assay for Leukemic Cell Induced Bone Marrow Angiogenesis

      Yi Zheng, Yubing Sun, Xinwei Yu, Yue Shao, Ping Zhang, Guohao Dai and Jianping Fu

      Article first published online: 29 FEB 2016 | DOI: 10.1002/adhm.201501007

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      A microengineered 3D biomimetic culture system is developed to quantitatively study leukemic cell induced bone marrow angiogenesis in vitro. Rational design of the biomimetic culture system incorporating endothelial cells, leukemic cells, and bone marrow stromal fibroblasts provides an efficient biomimetic means to promote and visualize early angiogenic processes in a bone marrow like environment.

    3. Multifunctional Quantum Dot Nanoparticles for Effective Differentiation and Long-Term Tracking of Human Mesenchymal Stem Cells In Vitro and In Vivo

      Jinming Li, Wayne Yukwai Lee, Tianyi Wu, Jianbin Xu, Kunyu Zhang, Gang Li, Jiang Xia and Liming Bian

      Article first published online: 25 FEB 2016 | DOI: 10.1002/adhm.201500879

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      The quantum dots (QDs) are conjugated with RGD peptide and β-cyclodextrin (β-CD) to co-deliver siRNA and small molecule for enhancing the differentiation and long-term tracking of human mesenchymal stem cells (hMSCs). The RGD peptide and β-CD conjugation of QDs not only promote the cellular uptake of nanocarriers but also enable the co-delivery of siRNA and small molecules into hMSCs by nanocarriers, thereby significantly enhancing the differentiation of hMSCs in vitro and in vivo. Furthermore, the fluorescent QDs allow tracking of the hMSCs in vivo for 21 days, providing crucial insight to the behaviors of stem cells after implantation.

    4. Differentiation Induction of Mouse Neural Stem Cells in Hydrogel Tubular Microenvironments with Controlled Tube Dimensions

      Hiroaki Onoe, Midori Kato-Negishi, Akane Itou and Shoji Takeuchi

      Article first published online: 25 FEB 2016 | DOI: 10.1002/adhm.201500903

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      Differentiation induction of mouse neuronal stem cells in a geometrically controlled tubular 3D microenvironment is examined. The tubular microenvironment with a diameter of less than ≈100 μm contributes to forming highly viable and aligned neural tissue. This system can provide an effective tool for constructing microfiber-shaped neural tissues with controlled differentiation induction.

    5. Gelatin Microspheres as Vehicle for Cardiac Progenitor Cells Delivery to the Myocardium

      Dries A. M. Feyen, Roberto Gaetani, Janine Deddens, Danielle van Keulen, Chantal van Opbergen, Michelle Poldervaart, Jacqueline Alblas, Steven Chamuleau, Linda W. van Laake, Pieter A. Doevendans and Joost P. G. Sluijter

      Article first published online: 23 FEB 2016 | DOI: 10.1002/adhm.201500861

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      Gelatin microspheres are perfectly fitted for the delivery of stem cells to the heart. The biocompatibility of these micro­carriers allows for cardiac progenitor cells attachment to their surface. Once the cellular cargo is loaded, microcarriers can effectively improve the retention and survival of the attached cells. Additionally, their size allows for administration through a clinically relevant noninvasive cardiac injection-catheter.

  24. Communications

    1. Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes

      Subhamoy Das, Anthony J. Monteforte, Gunjan Singh, Marjan Majid, Michael B. Sherman, Andrew K. Dunn and Aaron B. Baker

      Article first published online: 18 FEB 2016 | DOI: 10.1002/adhm.201500993

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      Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype.

  25. Full Papers

    1. A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum

      Dillip K. Bishi, Santosh Mathapati, Jayarama R. Venugopal, Soma Guhathakurta, Kotturathu M. Cherian, Rama S. Verma and Seeram Ramakrishna

      Article first published online: 18 FEB 2016 | DOI: 10.1002/adhm.201500897

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      Development of a patient-inspired hepatocyte-scaffold composite is reported. Hepatocyte growth factor-enriched sera obtained from cardiac failure patients with secondary hyperbilirubinemia are used to induce hepatic commitment of bone marrow-derived mesenchymal stem cells of same individuals on an electrospun fibrous mesh of poly-l-lactic acid (PLLA)/gelatin. This generates metabolically competent hepatocyte-like cells on fibrous scaffold, which can have future therapeutic implication to restore damaged liver functions.

    2. Multiwalled Carbon Nanotubes Inhibit Tumor Progression in a Mouse Model

      Lorena García-Hevia, Juan C. Villegas, Fidel Fernández, Íñigo Casafont, Jesús González, Rafael Valiente and Mónica L. Fanarraga

      Article first published online: 11 FEB 2016 | DOI: 10.1002/adhm.201500753

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      Multiwalled carbon nanotubes (MWCNTs) and microtubules share many properties that prompt their intracellular association. Here, it is shown how single intratumoral doses of serum-functionalized MWCNTs produce significant anti-tumoral effects in melanoma resistant tumors. Thus, MWCNTs represent a possible solution for the generation of new ground-breaking chemotherapies.


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