Complex 3D‐Printed Microchannels within Cell‐Degradable Hydrogels

3D‐printing is emerging as a technology to introduce microchannels into hydrogels, for the perfusion of engineered constructs. Although numerous techniques have been developed, new techniques are still needed to obtain the complex geometries of blood vessels and with materials that permit desired cellular responses. Here, a printing process where a shear‐thinning and self‐healing hydrogel “ink” is injected directly into a “support” hydrogel with similar properties is reported. The support hydrogel is further engineered to undergo stabilization through a thiol‐ene reaction, permitting (i) the washing of the ink to produce microchannels and (ii) tunable properties depending on the crosslinker design. When adhesive peptides are included in the support hydrogel, endothelial cells form confluent monolayers within the channels, across a range of printed configurations (e.g., straight, stenosis, spiral). When protease‐degradable crosslinkers are used for the support hydrogel and gradients of angiogenic factors are introduced, endothelial cells sprout into the support hydrogel in the direction of the gradient. This printing approach is used to investigate the influence of channel curvature on angiogenic sprouting and increased sprouting is observed at curved locations. Ultimately, this technique can be used for a range of biomedical applications, from engineering vascularized tissue constructs to modeling in vitro cultures.     

Capturing Complex Protein Gradients on Biomimetic Hydrogels for Cell‐Based Assays

A versatile strategy to rapidly immobilize complex gradients of virtually any desired protein on soft poly(ethylene glycol) (PEG) hydrogel surfaces that are reminiscent of natural extracellular matrices (ECM) is reported. A microfluidic chip is used to generate steady‐state gradients of biotinylated or Fc‐tagged fusion proteins that are captured and bound to the surface in less than 5 min by NeutrAvidin or ProteinA, displayed on the surface. The selectivity and orthogonality of the binding schemes enables the formation of parallel and orthogonal overlapping gradients of multiple proteins, which is not possible on conventional cell culture substrates. After patterning, the hydrogels are released from the microfluidic chip and used for cell culture. This novel platform is validated by conducting single‐cell migration experiments using time‐lapse microscopy. The orientation of cell migration, as well as the migration rate of primary human fibroblasts, depends on the concentration of an immobilized fibronectin fragment. This technique can be readily applied to other proteins to address a wealth of biological questions with different cell types.     

Hybrid 3D Printing of Synthetic and Cell‐Laden Bioinks for Shape Retaining Soft Tissue Grafts

Despite recent advances in clinical procedures, the repair of soft tissue remains a reconstructive challenge. Current technologies such as synthetic implants and dermal flap autografting result in inefficient shape retention and unpredictable aesthetic outcomes. 3D printing, however, can be leveraged to produce superior soft tissue grafts that allow enhanced host integration and volume retention. Here, a novel dual bioink 3D printing strategy is presented that utilizes synthetic and natural materials to create stable, biomimetic soft tissue constructs. A double network ink composed of covalently cross‐linked poly(ethylene) glycol and ionically cross‐linked alginate acts as a physical support network that promotes cell growth and enables long‐term graft shape retention. This is coupled with a cell‐laden, biodegradable gelatin methacrylate bioink in a hybrid printing technique, and the composite scaffolds are evaluated in their mechanical properties, shape retention, and cytotoxicity. Additionally, a new shape analysis technique utilizing CloudCompare software is developed that expands the available toolbox for assessing scaffold aesthetic properties. With this dynamic 3D bioprinting strategy, complex geometries with robust internal structures can be easily modulated by varying the print ratio of nondegradable to sacrificial strands. The versatility of this hybrid printing fabrication platform can inspire the design of future multimaterial regenerative implants.     

Tissue Engineered Bio‐Blood‐Vessels Constructed Using a Tissue‐Specific Bioink and 3D Coaxial Cell Printing Technique: A Novel Therapy for Ischemic Disease

Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.     

Versatile Functionalization of the Micropatterned Hydrogel of Hyperbranched Poly(ether amine) Based on “Thiol‐yne” Chemistry

The functionalization of a hydrogel with target molecules is one of the key steps in its various applications. Here, a versatile approach is demonstrated to functionalize a micropatterned hydrogel, which is formed by “thiol‐yne” photo‐click reaction between the yne‐ended hyperbranched poly(ether amine) (hPEA‐yne) and thiol‐containing polyhedral oligomeric silsesquioxane (PEG‐POSS‐SH). By controlling the molar ratio between hPEA‐yne and PEG‐POSS‐SH, patterned hydrogels containing thiol or yne groups are obtained. A series of thiol‐based click chemistry such as “thiol‐epoxy”, “thiol‐halogen”, “thiol‐ene”, and “thiol‐isocyanate” are used to functionalize the thiol‐containing hydrogel (Gel‐1), while the yne‐containing hydrogel (Gel‐2) is functionalized through a typical copper‐catalysed alkyne‐azide reaction (CuAAC). FTIR, UV‐vis spectra and confocal laser scanning microscopy (CLSM) are used to trace these click reactions. Due to the selective adsorption to the hydrophilic dyes, the obtained patterned hydrogel of hPEA modified with fluorescence dye is further demonstrated in application for the recognition of guest molecules.     

Bio‐Hybrid Tumor Cell‐Templated Capsules: A Generic Formulation Strategy for Tumor Associated Antigens in View of Immune Therapy

For the development of effective anti‐cancer vaccines, tumor associated antigens need to be internalized by antigen presenting cells alongside specific co‐stimulatory signals. Interestingly, relative to soluble antigens, nano‐ and micro‐particulate antigens are much better presented to CD8 T cells, a crucial step in the induction of cytotoxic T cells that can eliminate malignant cells. In this regard, a generic strategy to encapsulate cancer cell derived proteins into a particulate delivery system would be of high interest. Here we present a versatile approach to incorporate cancer cell proteins into polymeric capsules using the cells themselves as templates for layer‐by‐layer assembly of complimentary interacting species. After coating, the cells are killed by hypo‐osmotic treatment leading to bio‐hybrid capsules loaded with cell lysate. Particular focus is devoted in this work on choosing the optimal coating components and conditions to maximize cell membrane integrity during the coating process, minimize pre‐mature protein release and achieve optimal encapsulation of cell lysate upon lysis of the cells. To further underline the generic nature of our approach, we demonstrate that heat shock proteins, important immune‐activators, can be induced and encapsulated into the bio‐hybrid capsules.     

Microtribological and Nanomechanical Properties of Switchable Y‐Shaped Amphiphilic Polymer Brushes

We have characterized the morphology and nanomechanical properties of surface‐grafted nanoscale layers consisting of Y‐shaped binary molecules with one polystyrene (PS) arm and one poly(acrylic acid) (PAA) arm. We examined these amphiphilic brushes in fluids (in‐situ visualization), and measured their microtribological characteristics as a function of chemical composition. Atomic force microscopy (AFM)‐based nanomechanical testing has shown that nanoscale reorganization greatly influences the adhesion and elastic properties of the nanoscale brush layer. In water, a bimodal distribution of the elastic modulus, arising from the mixed chemical composition of the topmost layer, is observed. In contrast, the top layer is completely dominated by PS in toluene. As a result of this reorganization, the Y‐shaped‐brush layer exhibits a dramatic variation in the friction and wear properties after exposure to different solvents. Unexpectedly, the tribological properties are enhanced for the hydrophilic and polar, PAA‐dominated, surface, which shows a lower friction coefficient and higher wear stability, despite higher adhesion and heterogeneous surface composition. We suggest that this unusual behavior is caused by the combination of the presence of a thicker water layer on the PAA‐enriched surface that acts as a boundary lubricant and the glassy state of the PAA chains.     

Thermodynamic and Kinetic Tuning of Block Copolymer Based on Random Copolymerization for High‐Quality Sub‐6 nm Pattern Formation

The precisely controllable self‐assembly phenomenon of block copolymers (BCPs) has garnered much attention because it yields well‐defined periodic nanostructures with a periodicity of 5–50 nm. However, from both thermodynamic and kinetic viewpoints, it still remains a challenge to develop a BCP material that can provide sub‐10 nm resolution, high pattern quality, fast pattern formation, and sufficient etch selectivity. To address these challenges, this study reports a BCP system containing a random‐copolymerized block (poly(2‐vinylpyridine‐co‐4‐vinylpyridne)‐b‐poly(dimethylsiloxane) (P(2VP‐co‐4VP)‐b‐PDMS)) that can provide sub‐6 nm resolution, 3σ line edge roughness of 0.89 nm, sub‐1‐min assembly time, and a high etch selectivity over 10. Calculation of the Flory–Huggins interaction parameter (χ) based on Leibler's mean‐field theory and small‐angle X‐ray scattering measurement data confirms the gradual tunability of χ with the controlled addition of 4VP fraction in the P(2VP‐co‐4VP) block. While guaranteeing kinetically fast self‐assembly within one minute using microwave annealing, the best pattern quality resulting from the thermodynamic suppression of line edge fluctuation is achieved with a 4VP weight fraction of 33% in the random‐copolymerized block. This approach enables systematical control of sub‐6 nm scale BCP self‐assembly and will provide a practical patterning solution for diverse nanostructures and devices.     

A Gel‐Based Model of Selective Cell Motility: Implications for Cell Sorting,Diagnostics, and Screening

The ability to precisely control cell‐loaded material systems is essential for in vitro testing of novel therapeutics poised to advance to clinic. In this report, unique patterns of cell migration are devised into an in vitro gel‐in‐gel model for the purpose of obtaining cell response data to potentially therapeutic chemical agonists. The model consists of co‐cultures in a cell‐loaded microgel invading an acellular “sorting” gel. Material properties including biophysical and chemical compositions of the sorting gel are carefully controlled to guide a desired cell‐specific behavior, leading to massive tumor cell invasion by amoeboid migration mechanisms. Optical transparency enables straightforward and high‐throughput measurements of outgrowth response in the presence of either chemical and photoradiation therapy. Important dosing and drug sensitivity information are obtained with the gel‐in‐gel model using no more than a light microscope, without further need for arduous genomic or proteomic screening of the tissue samples.     

Self‐optimization of handover parameters for dynamic small‐cell networks

Seamless handover is an essential feature of cellular networks. For small‐cell networks, effective handover becomes particularly challenging. If some cells may be activated and deactivated dynamically, effective handover handling will become even more difficult. A key factor of good handover performance is “handover timing,” that is, making handover decision at a right time. If handover is executed too early or too late, users will experience temporary link disconnection, called radio link failure (RLF). Handover timing is controlled by handover parameters, which are set by the network. RLF prevention is directly related to the proper configuration of these parameters. In this paper, we propose a self‐optimization scheme that adjusts the handover parameters to minimize RLFs for dynamic small‐cell networks. Our scheme first detects the types of RLF and then adjusts the handover parameters according to the types of RLF. Unlike most existing schemes, our scheme adjusts both system common parameters and cell‐specific parameters together. In certain situations, such as when two adjacent cells do not have sufficient coverage overlap, RLFs may not be reduced to a satisfactory level by the handover parameter adjustment alone. To deal with such a case, our scheme adjusts the cell coverage in conjunction with the handover parameter optimization. The simulation results show that the proposed scheme can virtually eliminate RLFs. Copyright © 2013 John Wiley & Sons, Ltd.     

Silicon‐Based Laser Desorption Ionization Mass Spectrometry for the Analysis of Biomolecules: A Progress Report

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) is widely used in the biomedical field for the label‐free analysis of molecules such as drugs, lipids, peptides, proteins, and biological tissues for molecular imaging. However, organic matrices used in traditional MALDI‐MS applications introduce excessive interferences in the low m/z range. For this reason, nanostructured materials—and in particular silicon‐based LDI strategies—have become a promising alternative, since they provide a much weaker background. Herein, the recent developments in fabrication, functionalization, and practical applications of silicon‐based LDI‐MS methods are reviewed. Also the basic requirements of silicon‐based substrates for optimal LDI analysis by providing an overview of the LDI mechanisms that use silicon‐based substrates instead of organic matrices are reported. Finally, the considerable potential of silicon‐based substrates is discussed, giving suggestions for topics for future research.     

Facile Nondestructive Assembly of Tyrosine‐Rich Peptide Nanofibers as a Biological Glue for Multicomponent‐Based Nanoelectrode Applications

Achieving the nondestructive assembly of carbon nanoelectrodes with multiple components in a scalable manner enables effective electrical interfaces among nanomaterials. Here, a facile nondestructive multiscale assembly of multicomponent nanomaterials using self‐assembled tyrosine‐rich peptide nanofibers (TPFs) as a biological glue is reported. The versatile functionalities of the rationally devised tyrosine‐rich short peptide allow for (1) self‐assembly of the peptide into nanofibers using noncovalent interactions, followed by (2) immobilization of spatially distributed metal nanoparticles on the nanofiber surface, and (3) subsequent assembly with graphitic nanomaterials into a percolated network‐structure. This percolated network‐structure of silver nanoparticle (AgNP)‐decorated peptide nanofibers with imbedded single‐walled carbon nanotubes (SWNTs) proves to be a versatile nanoelectrode platform with excellent processability. The SWNT–TPF–AgNP assembly, when utilized as a flexible and transparent multicomponent electronic film, was quite effective for enhancing direct electron transfer (DET) as verified for a third‐generation glucose sensor composed of this film. The simple solution process used to produce the functional nanomaterials could provide a new platform for scalable manufacturing of novel nanoelectrode materials forming effective electrical contacts with molecules from diverse biological systems.     

Self‐Crosslink Method for a Straightforward Synthesis of Poly(Vinyl Alcohol)‐Based Aerogel Assisted by Carbon Nanotube

As a new concept, a self‐crosslink mechanism for hydrothermal synthesis of poly(vinyl alcohol) (PVA) aerogel, assisted by multiwall carbon nanotubes, is reported. PVA, working as a low‐cost and commercially available raw material, exempts the complicated synthesis process and reserves its nontoxic nature since no organic crosslinkers are used in the synthesis process. The crosslink density and many other properties of the products can be easily tuned by simply altering the concentration of PVA precursors, which is considered to be another feature of our method. Dehydration between hydroxyl groups occurs in the hydrothermal process, leading to a reverse wettability of the products from hydrophilic to hydrophobic, thus their absorbing capacity for several organic solvents, such as bean oil and crude oil, is investigated. The absorbate has 10–52 times the original weight of the aerogel. As exhibited by the cytotoxic tests, the product has neglectable toxicity, suitable for application in environmental bioengineering. Furthermore, the product can be used as a facile substrate for transformation into conductive aerogel by in situ hybridizing with polypyrrole, showing a conductivity of 0.16 S m^?1. As it is rich in hydroxyl groups, the aerogels are believed to be further functionalized by the reactions related to the hydroxyl group.     

A 3‐in‐1 doping process for interdigitated back contact solar cells exploiting the understanding of co‐diffused dopant profiles by use of PECVD borosilicate glass in a phosphorus diffusion

Boron and phosphorus doping of crystalline silicon using a borosilicate glass (BSG) layer from plasma‐enhanced chemical vapor deposition (PECVD) and phosphorus oxychloride diffusion, respectively, is investigated. More specifically, the simultaneous and interacting diffusion of both elements through the BSG layer into the silicon substrate is characterized in depth. We show that an overlying BSG layer does not prevent the formation of a phosphorus emitter in silicon substrates during phosphorus diffusion. In fact, a BSG layer can even enhance the uptake of phosphorus into a silicon substrate compared with a bare substrate. From the understanding of the joint diffusion of boron and phosphorus through a BSG layer into a silicon substrate, a model is developed to illustrate the correlation of the concentration‐dependent diffusivities and the emerging diffusion profiles of boron and phosphorus. Here, the in‐diffusion of the dopants during diverse doping processes is reproduced by the use of known concentration dependences of the diffusivities in an integrated model. The simulated processes include a BSG drive‐in step in an inert and in a phosphorus‐containing atmosphere. Based on these findings, a PECVD BSG/capping layer structure is developed, which forms three different n⁺⁺−, n⁺− and p⁺−doped regions during one single high temperature process. Such engineered structure can be used to produce back contact solar cells. Copyright © 2016 John Wiley & Sons, Ltd.     

Simple Detection Based on Soft‐Limiting for Binary Transmission in a Mixture of Generalized Normal‐Laplace Distributed Noise and Gaussian Noise

In this letter, a simplified suboptimum receiver based on soft‐limiting for the detection of binary antipodal signals in non‐Gaussian noise modeled as a generalized normal‐Laplace (GNL) distribution combined with Gaussian noise is presented. The suboptimum receiver has low computational complexity. Furthermore, when the number of diversity branches is small, its performance is very close to that of the Neyman‐Pearson optimum receiver based on the probability density function obtained by the Fourier inversion of the characteristic function of the GNL‐plus‐Gaussian distribution.