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An internally switched model of ocular tracking with prediction.

Ocular tracking of targets in biological systems involves switching between two strategies: slow pursuit and fast corrective saccades producing pursuit nystagmus. Here, a symmetric (bilateral) controller is used as a model for the oculomotor control system (OCS) to drive two cameras on a robotic head. It relies, as in biology, on internal switching in shared premotor circuits to alternate automatically between the two types of movements comprising nystagmus. The symmetric structural concept is gaining acceptance as evidence points to sharing of both fast phase and slow phase control in brainstem structures previously thought to be solely involved in one mode alone. This bilateral OCS model is a parsimonious design that is at once biomimetic and analytically simple. We extend prior results by incorporating more biological clues from floccular projections to establish rudimentary prediction mechanisms for both slow and fast phases; prediction is achieved by using retinal slip, which contains target velocity information. This provides a more accurate replication of the difference between fast phase and slow phase dynamics, and considers neural activity profiles in the superior colliculus to refine the controller performance. The resulting controller eliminates the need for saccades in steady state for low frequency inputs, and each saccade now has better accuracy, despite visual delays.

Animals↗

Cultivation of endothelial progenitor cells on fibrin matrix and layering on dacron/polytetrafluoroethylene vascular grafts.

Completely biological tissue-engineered vascular graft is an upcoming substitute for damaged blood vessel, but its clinical use is currently limited due to poor mechanical strength. Therefore, at present, polymeric small-diameter vascular grafts lined with endothelial cells (ECs) to reduce graft thrombosis may be a more viable option. Successful construction of EC-seeded artificial grafts faces some challenges such as (i) retention of endothelial lining; and (ii) availability of differentiated autologous cells. Biomaterial surfaces that are modified by depositing extracellular matrix (ECM) components may stabilize cells in the lumen against forces of blood flow. Adult stem cells such as endothelial progenitor cells (EPCs) circulate in the blood and they usually attach to the exposed matrix at the injured blood vessel site. Depending on the signaling capabilities of ECM, cells may differentiate into ECs,, and if a similar composition of the matrix is provided in vitro, EPCs isolated from blood might get differentiated and thus autologous cells for tissue engineering may be obtained. In this in vitro study, ECM scaffold consisting of biomolecules such as fibrin, fibronectin, and gelatin along with growth factors is found to have supported differentiation of EPC into EC. Further, the ECM precoated on Dacron and polytetrafluoroethylene is found to have supported the formation of EC monolayer that synthesized nitric oxide, and resisted shear stress. Thus, biomimetic fibrin composite is found to be suitable not only to seed cells on currently available artificial grafts but also to obtain differentiated EC from EPC.

Animals↗

Tissue engineered nerve constructs: where do we stand?

Driven by enormous clinical need, interest in peripheral nerve regeneration has become a prime focus of research and area of growth within the field of tissue engineering. While using autologous donor nerves for bridging peripheral defects remains today's gold standard, it remains associated with high donor site morbidity and lack of full recovery. This dictates research towards the development of biomimetic constructs as alternatives. Based on current concepts, this review summarizes various approaches including different extracellular matrices, scaffolds, and growth factors that have been shown to promote migration and proliferation of Schwann cells. Since neither of these concepts in isolation is enough, although each is gaining increased interest to promote nerve regeneration, various combinations will need to be identified to strike a harmonious balance. Additional factors that must be incorporated into tissue engineered nerve constructs are also unknown and warrant further research efforts. It seems that future directions may allow us to determine the "missing link".

Animals↗

The nanopore connection to cell membrane unitary permeability.

Artificial nanopores have recently emerged as versatile tools for analyzing and sorting single molecules at high speed. However, the biological cell has already developed a large set of sophisticated protein nanopores that are able to selectively translocate all types of molecules through membranes. Therefore, hybrid devices combining artifical solid-state with biomimetic protein nanopores appear to us as a particularly promising approach to the creation of powerful diagnostic, preparative and therapeutic devices. Here, we discuss a technique, optical single-transporter recording (OSTR), in which arrays of artificial micropores and nanopores are employed to analyze protein nanopores of cellular membranes. After briefly summarizing some salient features of OSTR, the technique is compared with the electrical patch clamp method and the first results of our efforts to amalgamate optical and electrical recording are described. Finally, prospects for combining OSTR with 4Pi microscopy, single-molecule fluorescence spectroscopy and fluorescence correlation spectroscopy are discussed.

Biomimetic Materials↗

Amelogenin control over apatite crystal growth is affected by the pH and degree of ionic saturation.

OBJECTIVE: To study the mechanisms which promote the interactions of amelogenin proteins with the forming mineral to establish suitable conditions for the biomimetic synthesis of enamel in vitro. DESIGN: Saturated calcium phosphate solutions were used in conjunction with recombinant amelogenin proteins to induce mineral formation on glass-ceramics substrates containing oriented fluoroapatite crystals (FAP). The height of mineral layers formed on these substrates within 24 h was measured by atomic force microscopy (AFM). EXPERIMENTAL VARIABLES: The effect of protein concentration, pH and degree of saturation (DS) on the growth of apatite mineral was evaluated. Mineralization experiments were performed at 0, 0.4 and 1.6 mg/ml amelogenin concentrations. Mineralization solutions were used at pH values of 6.5, 7.4, 8.0 and 8.8 and DS of calcium and phosphate between 9 and 13. OUTCOME MEASURE: Height and morphology of mineralized layer formed on glass-ceramic substrates as determined from AFM measurements. RESULTS: Homogeneous nucleation and crystal growth of thin layers on the FAP were observed, when calcium and phosphate ions were added. The height of these layers grown on (001) planes of FAP was strongly dependent on the protein concentration and pH. At concentrations of 0 and 0.4 mg/ml crystal grew 5-15 nm on the FAP, while they grew approximately to 200 nm at 1.6 mg/ml. The enhanced crystal growth was observed only at pH 6.5, 7.4 and 8.0, while layers only 20 nm thick were obtained at pH 8.8. An increase in DS resulted in uncontrolled growth of calcium phosphate mineral covering large areas of the substrate. CONCLUSIONS: Protein concentration, pH and the saturation of the mineralizing solution need to be considered carefully to provide suitable conditions for amelogenin-guided growth of apatite crystals.

Amelogenesis↗

Tissue engineering osteochondral implants for temporomandibular joint repair.

Tissue engineering has provided an alternative to traditional strategies to repair and regenerate temporomandibular joints (TMJ). A successful strategy to engineer osteochondral tissue, such as that found in the TMJ, will produce tissue that is both biologically and mechanically functional. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match patient and defect site geometry. The objective of this study was to demonstrate how scaffold design, materials, and biological factors can be used in an integrated approach to regenerate a multi-tissue interface. IBD and SFF were first used to create biomimetic scaffolds with appropriate bulk geometry and microarchitecture. Biphasic composite scaffolds were then manufactured with the same techniques and used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-l-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 in the ceramic phase and fully differentiated chondrocytes in the polymeric phase, and were subcutaneously implanted into mice. Following implantation in the ectopic site, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects and, ultimately, the TMJ.

Animals↗

Inspirations from biological optics for advanced photonic systems.

Observing systems in nature has inspired humans to create technological tools that allow us to better understand and imitate biology. Biomimetics, in particular, owes much of its current development to advances in materials science and creative optical system designs. New investigational tools, such as those for microscopic imaging and chemical analyses, have added to our understanding of biological optics. Biologically inspired optical science has become the emerging topic among researchers and scientists. This is in part due to the availability of polymers with customizable optical properties and the ability to rapidly fabricate complex designs using soft lithography and three-dimensional microscale processing techniques.

Animals↗

Microscopy and quantitative morphology of aluminum silicate nanoparticles grown on organic templates.

Biomimetic synthesis of ceramic materials is increasing in popularity because it offers many advantages. In this work, aluminum silicate nanoparticles were obtained on a self-assembled organic multilayer at near room temperature (30 < or = T < or = 50 degrees C) and at atmospheric pressure. Morphological and microanalytical characterization was carried out by means of transmission electron microscopy and subsequent image analysis. The roles of some process parameters such as template type, reactant concentration, [Al]:[Si] molar ratio, number of initiation steps (IS) of mineralization, and reaction time (rt) were assessed by comparing images, diffraction patterns, and EDX spectra. Generally, the Si-rich phase exhibited higher crystallinity, whereas the Al-rich phase was mostly amorphous. Crystal structure resulted with rt > or = 4 days for template-grown materials. Images of materials obtained at T = 50 degrees C, rt = 3 days, and 1 < or = IS < or = 4 were further analyzed by "spectrum enhancement," an algorithm based on the Fourier transform. Morphological indicators were extracted from suitably processed power spectral densities, a correlation matrix was formed, and multivariate statistics was carried out. Visual differences in nanoaggregate morphology were quantitatively translated. Materials were ranked by the spatial uniformity of nanoparticle distribution: the most uniform aggregates were those grown on templates by IS > or = 2. Univariate statistics validated the conclusion: the particles of those same materials had a narrower size distribution and sharper edges. This last property has been ascribed to crystalline structure, independently demonstrated by diffraction patterns.

Aluminum↗

Controlled silica synthesis inspired by diatom silicon biomineralization.

Silica becomes increasingly used in chemical, pharmaceutical, and (nano)technological processes, resulting in an increased demand for well-defined silicas and silica-based materials. The production of highly structured silica from cheap starting materials and under ambient conditions, which is a target for many researchers, is already realized in the formation of diatom biosilica, producing highly hierarchical ordered meso- and macropores silica structures. This notion formed the starting point in our integrative biomolecular and biomimetic study on diatom silicon biomineralization in which we have analyzed silica transformations and structure-direction in polymer-mediated silica syntheses using a combination of (ultra)small-angle X-ray scattering and (cryo)electron microscopy. Using bio-analogous reaction conditions and reagents, such as waterglass and (combinations of) polyethylene oxide (PEO) based polymers, we demonstrate in this review the synthesis of tailor-made mesoporous silicas in which we can, as in biosilica synthesis, control the morphological features of the resulting materials on the nanometer level as well as on the micrometer level.

Biomimetics↗

Bio-adhesive surfaces to promote osteoblast differentiation and bone formation.

Binding of integrin adhesion receptors to extracellular matrix components, such as fibronectin and type I collagen, activates signaling pathways directing osteoblast survival, cell-cycle progression, gene expression, and matrix mineralization. Biomimetic strategies exploit these adhesive interactions to engineer bio-inspired surfaces that promote osteoblast adhesion and differentiation, bone formation, and osseointegration. These emerging initiatives focus on directing integrin binding through presentation of bio-adhesive motifs derived from extracellular matrices. These biomolecular approaches provide promising strategies for the development of biologically active implants and grafting substrates for enhanced bone repair.

Biomimetic Materials↗

Artificial ommatidia by self-aligned microlenses and waveguides.

We report the fabrication of artificial ommatidia, the imaging units of insects' compound eyes, by use of polymer integrated optics. These biomimetic structures are obtained by configuring microlenses to play dual roles for self-writing of waveguides (during the fabrication) and collection of light (during the operation). The artificial ommatidium, consisting of a microlens, a spacer, and a waveguide, directly resembles the structure of its biological counterpart. Optical characterizations reveal single-peak angular sensitivity with a +/- 0.75 degrees acceptance angle that is comparable to those found in nature. Using geometric and physical optics, we also investigate the relationship between angular sensitivity and the geometry of artificial ommatidia.

Animals↗

Biodegradable scaffolds--delivery systems for cell therapies.

The use of cells as therapies for disease, repair and regeneration of tissues is one of the new challenges in modern therapeutics. To facilitate the ability to localise, condition and protect cells, biodegradable scaffolds are being developed that will improve the efficiency of these treatments. Thus, cell delivery systems, either scaffolds or capsules, play a pivotal role in the success of these techniques. This review discusses these novel approaches. The selection of scaffold materials is addressed alongside issues of biocompatibility. The current research developments in smart scaffolds, which focus on the formation of biomimetic scaffolds, new fabrication techniques capable of controlling architecture and microstructure of scaffolds, and the production of injectable and in situ crosslinked scaffolds, are outlined. Finally, the continuing challenges that will drive future research in the cell therapies are highlighted.

Animals↗

Soft contact lens biomaterials from bioinspired phospholipid polymers.

Soft contact lens (SCL) biomaterials originated from the discovery of a poly(2-hydroxyethyl methacrylate) (poly[HEMA])-based hydrogel in 1960. Incorporation of hydrophilic polymers into poly(HEMA) hydrogels was performed in the 1970-1980s, which brought an increase in the equilibrium water content, leading to an enhancement of the oxygen permeability. Nowadays, the poly(HEMA)-based hydrogels have been applied in disposable SCL. At the same time, high oxygen-permeable silicone hydrogels were produced, which made it possible to continually wear SCL. Recently, numerous trials for improving the water wettability of silicone hydrogels have been performed. However, little attention has been paid to improving their anti-biofouling properties and biocompatibility. Since biomimetic phospholipid polymers possess excellent anti-biofouling properties and biocompatibility they have the potential to play a valuable role in the surface modification of the silicone hydrogel. The representative phospholipid polymers containing a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit suppressed nonspecific protein adsorption, increased cell compatibility and contributed to blood compatible biomaterials. The MPC polymer coating on the silicone hydrogel improved its water wettability and biocompatibility, while maintaining high oxygen permeability compared with the original silicone hydrogel. Furthermore, the newly prepared phospholipid-type intermolecular crosslinker made it possible to synthesize a 100% phospholipid polymer hydrogel that can enhance the anti-biofouling properties and biocompatibility. In this review, the authors discuss how polymer hydrogels should be designed in order to obtain a biocompatible SCL and future perspectives.

Biocompatible Materials↗

Solid-phase synthesis of reactive peptide crosslinker by selective deprotection.

An effective and simple strategy for preparing peptide crosslinkers is described. An MMP-13 degradable peptide QPQGLAK-NH(2) was prepared on the solid-phase using Fmoc chemistry. The peptide crosslinker was synthesized on-bead by the coupling reaction between acrylic acid and the amine groups of glutamine and lysine residues. The synthetic procedure employed the acid-labile Fmoc-Lys (Mtt)-OH and base-labile Fmoc-AA-OH derivatives. Selective deprotection, of -Mtt and -Fmoc groups on-bead, freed the amine end-groups on glutamine and lysine residues for coupling reaction with acrylic acid while maintaining the peptide attached to the resin. Subsequent cleavage from the resin yielded a peptide crosslinker with two unsaturated acrylate end-groups with high yield and purity. This method can be generally employed for the synthesis of a wide range of peptides with one or more reactive groups for grafting in the fabrication of biomimetic scaffolds in tissue engineering applications.

Biomimetic Materials↗

Membrane interactions of host-defense peptides studied in model systems.

Host-defense, antibiotic peptides are believed to generate their cytolytic effects by interacting with the membranes of bacterial cells. Direct analyses of peptide interactions with real cellular membranes are difficult, however, due to the high complexity of physiological membranes. This review summarizes experimental work aiming to understand peptide-membrane interactions and their relationships with the peptides' biological actions using specific model systems. Varied model assemblies have been constructed that generally aim to mimic the fundamental lipid bilayer organization of the membrane. The model systems we will describe include multilamellar and unilamellar vesicles, planar lipid bilayers, lipid monolayers and micelles, and colorimetric biomimetic membranes. The different artificial models have facilitated examination of specific biological or chemical parameters affecting peptide action, for example the effect of membrane lipid composition on peptide affinities and membrane penetration, the relationship between membrane fluidity and peptide interactions, the conformations of active peptides, and other factors. We evaluate the strengths and limitations of the various approaches, and point to future directions in the field.

Antimicrobial Cationic Peptides↗

Organotypic keratinocyte-fibroblast cocultures on a bilayer gelatin scaffold as a model of skin equivalent.

The skin consists of epidermis and dermis. In order to develop a biomimetic material for more realistic tissue regeneration, we fabricated a double layer gelatin sponge with different pore sizes by freeze-drying at different temperatures -20 [symbol: see text] and -196 [symbol: see text], respectively. A pseudo microporous structure, which provided the paracrine crosstalk in epithelial-mesenchymal interactions similar to the basement membrane in epidermal-dermal junction was formed between this two compartment. Chrondroitin-6-Sulphate (C-6-S) and hyaluronic acid (HA) were incorporated within the gelatin scaffold to create an appropriate microenvironment for cell proliferation and migration. The mechanical strength of gelatin sponges was improved by cross-linking of gelatin with carbodiimide in 95% ethanol solution two times. The lattice structure and pore sizes were evaluated by SEM to confirm that the interconnected porous structures were retained. We chose a dynamic spinner flask seeding method for more even distribution followed by a culture system in the air-liquid interface cultured for 21 days. Differentiation and phenotypic expression of keratinocytes were investigated by histological analysis and immunohistochemical identification. In this study, we found multiple epidermis-like layers constructed by cultured keratinocytes. It is suggested that the bi-layer scaffolds have the potential to be used as skin equivalents for application in burn wounds. In the future, the qualitative of chemical reagents and in vivo animal model tests will be evaluated.

Animals↗

Integrating dental anatomy and biomaterials: an innovative use of composite resin.

As part of the new integrated curriculum at the New York University College of Dentistry, a pilot program uses composite resins to teach dental anatomy. The Department of Biomaterials and Biomimetics, in conjunction with the Department of Cariology and Operative Dentistry, has created a teaching module to replicate the morphology of a central incisor through the manipulation and placement of a composite resin.

Biocompatible Materials↗

Synthesis and evaluation of scaffolds prepared from chitosan fibers for potential use in cartilage tissue engineering.

Tissue engineering concepts and methodologies that employ biocompatible matrices or scaffolds have the potential to meet needs encountered in the repair of defects in articular cartilage. A desirable design parameter in the tissue engineering of cartilage in vitro is the development of seeded scaffolds with appropriate structure, composition, mechanical properties and durability that are similar to normal articular cartilage. Previous methods that have used freeze drying and lyophilization techniques to make foams and hydrogels have not met the scaffold characteristics (porosity, compressive elastic modulus, permeability and viscoelastic properties), which are required of scaffolds slated for use in cartilage tissue engineering applications. Thus there is an impetus to design and develop biomimetic scaffolds that mimic the native ECM of articular cartilage, and distribute strain in a bioresponsive manner to signal seeded chondrocytes to synthesize and organize ECM to result in material properties that are in range of natural cartilage. We have employed the method of electrospinning to prepare scaffolds with oriented and random fiber alignment.

Animals↗