SOFT‐MI: A novel microfabrication technique integrating soft‐lithography and molecular imprinting for tissue engineering applications

An innovative approach has been employed for the realization of bioactive scaffolds able to mimic the in vivo cellular microenvironment for tissue engineering applications. This method is based on the combination of molecular imprinting and soft‐lithography technology to enhance cellular adhesion and to guide cell growth and proliferation due to presence of highly specific recognition sites of selected biomolecules on a well‐defined polymeric microstructure. In this article polymethylmethacrylate (PMMA) scaffolds have been realized by using poly(dimethylsiloxane) (PDMS) microstructured molds imprinted with FITC‐albumin and TRITC‐lectin. In addition gelatin, an adhesion protein, was employed for the molecular imprinting of polymeric scaffolds for cellular tests. The most innovative aspect of this research was the molecular imprinting of whole cells for the development of substrates able to enhance the cell adhesion processes. Biotechnol. Bioeng. 2010;106: 804–817. © 2010 Wiley Periodicals, Inc.     

Double Emulsion Generation Using a Polydimethylsiloxane (PDMS) Co-axial Flow Focus Device

Double emulsions are useful in a number of biological and industrial applications in which it is important to have an aqueous carrier fluid. This paper presents a polydimethylsiloxane (PDMS) microfluidic device capable of generating water/oil/water double emulsions using a coaxial flow focusing geometry that can be fabricated entirely using soft lithography. Similar to emulsion devices using glass capillaries, double emulsions can be formed in channels with uniform wettability and with dimensions much smaller than the channel sizes. Three dimensional flow focusing geometry is achieved by casting a pair of PDMS slabs using two layer soft lithography, then mating the slabs together in a clamshell configuration. Complementary locking features molded into the PDMS slabs enable the accurate registration of features on each of the slab surfaces. Device testing demonstrates formation of double emulsions from 14 µm to 50 µm in diameter while using large channels that are robust against fouling and clogging.     

细胞微系统技术及其应用

细胞微系统技术研究是目前细胞生物学、微系统科学及药物筛选等学科交叉领域的一个研究热点,其综合利用了微系统平台技术,将细胞的培养、观测和分析在微系统平台上完成,丰富了细胞研究方法,为细胞研究提供了一个全新的研究平台。现对目前细胞微系统研究中几种典型的方法,如立体微结构模型、软光刻、微流体、芯片毛细管电泳、微电极等进行综述,并阐述其在细胞生物学、生命科学等领域相关研究中的应用。     

Sensors for bioanalytes by imprinting—Polymers mimicking both biological receptors and the corresponding bioparticles

Structuring of thin polymer layers by soft lithography with template bioparticles results in the formation of selective surface cavities, leading to highly effective sensor systems when combined with mass-sensitive transducers, especially QCM. These sensors allow selective differentiation of various stages of development of yeast cells. In order to achieve a higher degree of standardisation, we fabricated plastic yeast cells and utilised them for the stamp imprinting procedures. These sensitive layers are capable of the differentiation between Saccharomyces cerevisiae and Saccharomyces bayanus. Aside from achieving the same sensitivity compared to the polymers that were structured using native cells, we realised further enhancement of selectivity exceeding a factor of three regarding the two cell strains. These ideas could also be transferred to develop a recognition system for the more flexible erythrocytes and therefore MIP-layers of polyvinylpyrrolidone were combined with QCMs. These devices provide sensor-based ABO blood group typing. Additionally, the differentiation of the subgroups A₁ and A₂ is shown with the generated MIP-layers that are decorated by high selectivity, namely the threefold frequency effect for the imprinted template, and negligible unspecific effects. Application of soft lithographic methods furthermore allows the design of artificial erythrocytes. These “plastic” blood cells posses an increased robustness compared to the native cells, thus opening up multiple novel strategies of surface patterning.     

A new generation of polymer nanoparticles for drug delivery.

One of the main interests of using polymer nanoparticles as drug carrier systems is to control the delivery of the drugs including their biodistribution. During the last decade, it was clearly demonstrated that surface properties of nanoparticles were the key factor which determined the in vivo fate of such a carrier. Thus, the purpose of this work was to develop a new method which allows the easy fabrication of nanoparticles with versatile surface properties using polysaccharides. This preparation was based on the use of a redox radical polymerization reaction applied for the first time to the emulsion polymerization of alkylcyanoacrylates in aqueous continuous media. The dispersion of nanoparticles was very stable. The nanoparticle surfaces were coated with polysaccharides and their characteristics can be modulated by the type and the molecular weight of the polysaccharides used during the synthesis. Interestingly the biological properties of the polysaccharide immobilized on the nanoparticle surface can be preserved opening very interesting perspectives for such nanoparticles. This method also offers a new strategy for the design of modular biomimetic nanoparticles as drug carrier systems with multiple functions. One of the applications considered in this work was to use these nanoparticles coupled with haemoglobin as an oxygen carrier.     

Lignin Laser Lithography: A Direct‐Write Method for Fabricating 3D Graphene Electrodes for Microsupercapacitors

In this work, a simple lignin‐based laser lithography technique is developed and used to fabricate on‐chip microsupercapacitors (MSCs) using 3D graphene electrodes. Specifically, lignin films are transformed directly into 3D laser‐scribed graphene (LSG) electrodes by a simple one‐step CO₂ laser irradiation. This step is followed by a water lift‐off process to remove unexposed lignin, resulting in 3D graphene with the designed electrode patterns. The resulting LSG electrodes are hierarchically porous, electrically conductive (conductivity is up to 66.2 S cm^?1), and have a high specific surface area (338.3 m² g^?1). These characteristics mean that such electrodes can be used directly as MSC electrodes without the need for binders and current collectors. The MSCs fabricated using lignin laser lithography exhibit good electrochemical performances, namely, high areal capacitance (25.1 mF cm^?2), high volumetric energy density (≈1 mWh cm^?3), and high volumetric power density (≈2 W cm^?3). The versatility of lignin laser lithography opens up the opportunity in applications such as on‐chip microsupercapacitors, sensors, and flexible electronics at large‐scale production.     

Metal nanoclusters: Protein corona formation and implications for biological applications

Metal nanoclusters (NCs) are a new type of nanoprobe with great potential in various biological applications. For biocompatible and efficient utilization of NCs, a thorough understanding of their interactions with biological systems is highly important. Herein, we focus on recent studies addressing interactions between metal NCs and proteins as well as implications for their further biological application. These findings show that protein adsorption not only affects the photophysical properties of NCs, but also influences their subsequent biological behavior, i.e., cellular uptake and cytotoxicity. Moreover, specific protein–NC interactions have also been harnessed to develop novel protein discrimination strategies.     

Methods for the topographical patterning and patterned surface modification of hydrogels based on hydroxyethyl methacrylate

Hydrogels have gained broad acceptance as a class of biocompatible materials. In this paper, we report the topographic patterning and regiospecific functionalization of hydrogel surfaces. Both photolithography and soft lithography are combined in a hybrid process to form these topographic features. By functionalization of a base layer surface followed by lithographic patterning steps, it is possible to introduce chemical functions to specific regions of the patterned surface. The model systems investigated were based on 2-hydroxyethyl methacrylate (HEMA), which is well-known for its low toxicity and widespread use in biomedical applications. Tests of Ni-NTA modified hydrogel surfaces showed successful binding of fluorescently labeled proteins to selected regions of the patterned hydrogel surface. These processes can be expanded to a wide range of monomer systems.     

细胞膜仿生修饰纳米粒肿瘤治疗的研究进展

大量研究证明,细胞膜仿生修饰通过将不同细胞膜包被于纳米粒表面,赋予纳米粒新的生物学功能.纳米粒被细胞膜仿生修饰后,获得了细胞膜表面丰富的蛋白质并保留了纳米粒的高载药能力,延长体内循环时间,使纳米粒具有逃避免疫系统,跨越各种生理屏障的能力.本文总结了近年来细胞膜仿生修饰纳米粒用于肿瘤治疗的最新进展,讨论了细胞膜仿生修饰纳...     

Interfacial Effects of Superhydrophobic Plant Surfaces： A Review

Nature is a huge gallery of art involving nearly perfect structures and properties over the millions of years of development. Many plants and animals show water-repellent properties with fine micro-structures, such as lotus leaf, water skipper and wings of butterfly. Inspired by these special surfaces, the artificial superhydrophobic surfaces have attracted wide attention in both basic research and industrial applications. The wetting properties of superhydrophobic surfaces in nature are affected by the chemical compositions and the surface topographies. So it is possible to realize the biomimetic superhydrophobic surfaces by tuning their surface roughness and surface free energy correspondingly. This review briefly introduces the physical-chemical basis of superhydrophobic plant surfaces in nature to explain how the superhydrophobicity of plant surfaces can be applied to different biomimetic functional materials with relevance to technological applications. Then, three classical effects of natural surfaces are classified： lotus effect, salvinia effect, and petal effect, and the promising strategies to fabricate biomimetic su- perhydrophobic materials are highlighted. Finally, the prospects and challenges of this area in the future are proposed.     

Profile Simulation and Fabrication of Gold Nanostructures by Separated Nanospheres with Oblique Deposition and Perpendicular Etching

This paper investigates in detail the profiles of the nanostructures fabricated by nanosphere lithography through oblique deposition and perpendicular etching. 2D or 3D nanostructures can be achieved by this cost-effective method. Because the optical response of a particular nanoparticle depends on its size and shape, this angle deposition method can produce various shapes of nanostructures, which are suitable for localized surface plasmon resonance biosensor applications. The nanostructure profiles under various deposition and etching conditions are simulated in our work. The calculated 3D profiles are verified by the 3D nanostructures fabricated in our experiments, and the calculated 2D profiles are in good agreement with the fabricated nanocrescents reported by another research group. This paper gives a full theoretical solution of the obtainable nanostructure shapes by nanosphere lithography utilizing oblique deposition and perpendicular etching.     

Invited review liquid crystal models of biological materials and silk spinning

A review of thermodynamic, materials science, and rheological liquid crystal models is presented and applied to a wide range of biological liquid crystals, including helicoidal plywoods, biopolymer solutions, and in vivo liquid crystals. The distinguishing characteristics of liquid crystals (self-assembly, packing, defects, functionalities, processability) are discussed in relation to biological materials and the strong correspondence between different synthetic and biological materials is established. Biological polymer processing based on liquid crystalline precursors includes viscoelastic flow to form and shape fibers. Viscoelastic models for nematic and chiral nematics are reviewed and discussed in terms of key parameters that facilitate understanding and quantitative information from optical textures and rheometers. It is shown that viscoelastic modeling the silk spinning process using liquid crystal theories sheds light on textural transitions in the duct of spiders and silk worms as well as on tactoidal drops and interfacial structures. The range and consistency of the predictions demonstrates that the use of mesoscopic liquid crystal models is another tool to develop the science and biomimetic applications of mesogenic biological soft matter.     

Biomimetic vibrissal sensing for robots

Active vibrissal touch can be used to replace or to supplement sensory systems such as computer vision and, therefore, improve the sensory capacity of mobile robots. This paper describes how arrays of whisker-like touch sensors have been incorporated onto mobile robot platforms taking inspiration from biology for their morphology and control. There were two motivations for this work: first, to build a physical platform on which to model, and therefore test, recent neuroethological hypotheses about vibrissal touch; second, to exploit the control strategies and morphology observed in the biological analogue to maximize the quality and quantity of tactile sensory information derived from the artificial whisker array. We describe the design of a new whiskered robot, Shrewbot, endowed with a biomimetic array of individually controlled whiskers and a neuroethologically inspired whisking pattern generation mechanism. We then present results showing how the morphology of the whisker array shapes the sensory surface surrounding the robot's head, and demonstrate the impact of active touch control on the sensory information that can be acquired by the robot. We show that adopting bio-inspired, low latency motor control of the rhythmic motion of the whiskers in response to contact-induced stimuli usefully constrains the sensory range, while also maximizing the number of whisker contacts. The robot experiments also demonstrate that the sensory consequences of active touch control can be usefully investigated in biomimetic robots.     

Biomechanics of Musculoskeletal System and Its Biomimetic Implications： A Review

Biological musculoskeletal system （MSK）, composed of numerous bones, cartilages, skeletal muscles, tendons, ligaments etc., provides form, support, movement and stability for human or animal body. As the result of million years of selection and evolution, the biological MSK evolves to be a nearly perfect mechanical mechanism to support and transport the human or animal body, and would provide enormously rich resources to inspire engineers to innovate new technology and methodology to develop robots and mechanisms as effective and economical as the biological systems. This paper provides a general review of the current status of musculoskeletal biomechanics studies using both experimental and computational methods. This includes the use of the latest three-dimensional motion analysis systems, various medical imaging modalities, and also the advanced rigid-body and continuum mechanics musculoskeletal modelling techniques. Afterwards, several representative biomimetic studies based on ideas and concepts inspired from the structures and biomechanical functions of the biological MSK are dis- cussed. Finally, the major challenges and also the future research directions in musculoskeletal biomechanics and its biomimetic studies are proposed.     

Non-covalent molecular imprinting with emphasis on its application in separation and drug development

The molecular imprinting technique can be defined as the formation of specific nano-sized cavities by means of template-directed synthesis. The resulting molecularly imprinted polymers (MIPs), which often have an affinity and a selectivity approaching those of antibody-antigen systems, have thus been coined "artificial antibodies." MIPs are characterized by their high specificity, ease of preparation, and their thermal and chemical stability. They have been widely studied in connection with many potential applications, including their use for separation and isolation purposes, as antibody mimics (biomimetic assays and sensors), as enzyme mimics, in organic synthesis, and in drug delivery. The non-covalent imprinting approach, developed mainly in Lund, has proven to be more versatile than the alternative covalent approach because of its preparation being less complicated and of the broad selection of functional monomers and possible target molecules that are available. The paper presents a review of studies of this versatile technique in the areas of separation and drug development, with emphasis being placed on work carried out in our laboratory.     

Advances in polymeric systems for tissue engineering and biomedical applications

The characteristics of tissue engineered scaffolds are major concerns in the quest to fabricate ideal scaffolds for tissue engineering applications. The polymer scaffolds employed for tissue engineering applications should possess multifunctional properties such as biocompatibility, biodegradability and favorable mechanical properties as it comes in direct contact with the body fluids in vivo. Additionally, the polymer system should also possess biomimetic architecture and should support stem cell adhesion, proliferation and differentiation. As the progress in polymer technology continues, polymeric biomaterials have taken characteristics more closely related to that desired for tissue engineering and clinical needs. Stimuli responsive polymers also termed as smart biomaterials respond to stimuli such as pH, temperature, enzyme, antigen, glucose and electrical stimuli that are inherently present in living systems. This review highlights the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers have also been discussed. The ultimate objective is to emphasize on these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.     

Microstructure of pretarsal pulvilli in shield bug Acanthosoma spinicolle (Heteroptera: Acanthosomatidae)

Shield bugs effectively attach themselves on both rough and smooth surfaces, but their advanced biological attachment devices have not been studied closely. Our fine structural examination of the attachment devices in the shield bug A. spinicolle reveals a unique system to achieve extraordinary adhesion that allows vertical climbing. Each appendage has a pair of tarsal claws that attach to rough substrates and a pair of pretarsal pulvilli that attach to smooth surfaces. Similar to other heteropteran insects, the pulvilli of this bug are categorized as a wet adhesion system, which makes use of an adhesive fluid from the pad secretion. However, this deformable pad creates a regular pattern of contact with the mating surface with a compact array of microfolds and setae with filamentous distal protrusions. To date, this distinctive microstructure in pulvilli pads has never been reported. These microstructural characteristics should be further studied to understand biological adhesion as well as create biomimetic applications.     

A fast, precise and low-cost replication technique for nano- and high-aspect-ratio structures of biological and artificial surfaces

Biological surfaces are multifunctional interfaces between the organisms and their environment. Properties such as the wettability and adhesion of particles are linked to the micro- and nanostructures of their surfaces. In this study, we used plant and artificial surfaces covered with wax crystals to develop a low-cost replication technique with high resolution. The technique is applicable for fragile surface structures, as demonstrated for three-dimensional wax crystals, and is fast to prevent shrinking of the biological material by water loss during the molding process. Thermal evaporation of octacosan-1-ol has been used to create microstructured surfaces with small platelets as templates for molding. Epoxy resin as filling material provided the smallest deviations from the original surface structures and can be used for replication of nanostructures as small as 4.5 nm. Contact angle measurements of leaves and their replicas show that this technique can be used to develop biomimetic surfaces with similar wettability as in the plant surfaces.