In the past, we have successfully designed and produced a variety of engineered spider silk-like proteins (eADF3 and eADF4) based upon the primary sequence of the natural dragline proteins ADF3 and ADF4 from the spider Araneus diadematus [1]. Genetically engineered spider silk proteins can be modified at the molecular level to optimize the biochemical and mechanical properties of the final product. Although engineered spider silk proteins can be processed into fibers using different spinning methods, our group is interested in the technical realization of a biomimetic approach. Here, we present an overview over our biomimetic fiber production process.

A facile electrophoretic deposition method was successfully applied to achieve novel nanoclay-reinforced polyacrylamide nanocomposite thin films. A special curled architecture of the re-aggregated nanoclay-platelets was identified, providing a possible source for realizing the interlocking mechanism in the nanocomposites. The curled architecture could be the result from strain releasing when the thin films were peeled off from the substrates. Through micro-/nano-indentation and in situ observation of the deformation during tensile test with an atomic force microscope (AFM), the localized deformation mechanism of the synthesized materials was investigated in further details. The results implied that a localized crack diversion mechanism worked in the synthesized nanocomposite thin films, which resembled its nature counterpart-nacre. The deformation behavior and fracture mechanism were discussed with reference to lamellar structure, interfacial strength between the nanoclays and the polyacrylamide matrix, and nanoclay agglomeration.

Poly(lactide) (PLA) and its copolymers degrade through hydrolysis into non-toxic and water soluble metabolic products in vivo. They are ideal materials for resorbable biomedical applications such as drug delivery and tissue engineering. However, these polymers are brittle and often need to be toughened. One of the most effective toughening methods is reactive blending, in which additives are dispersed into polymer matrices as small particles with strong bonding between the two materials. In this paper, we studied toughening poly(lactide-co-glycolide) (PLGA) through reactive blending with poly(trimethylene carbonate) (PTMC). We observed warm-like micelle or swollen warm-like micelle structures created during the reactive blending process with a twin screw extruder at high temperature. The micelle structures were orientated along the extrusion direction with their length ranging from 50 to 1000 nm and diameters about 50 nm. This structure could be produced only with a twin screw extruder. When a batch mixer was used, the PTMC additive (10 to 30 wt%) formed spheres with diameters on the order of 100-500 nm. The PLGA/PTMC copolymers formed in situ were responsible to this microstructure. The mechanical properties of this blend were significantly improved over the pure PLGA.

Nanoporous electrodes, such as those made from carbon or gold, can capture and release ionic analytes at concentrations near 1 mole per liter of pore volume through capacitive charging or electrochemically reversible adsorption. In vitro studies suggest that this phenomenon can be the basis for a noninvasive, precise, and programmable drug delivery method. It would eliminate the need for bulk fluid delivery to target tissue and require only a thin electrical connection, minimizing pain and tissue disruption. We have designed effective gold electrode assemblies and observed the depletion and release phenomena using electrochemical methods and charged dyes.

Poly(butylene fumerate) (PBF) and poly(butylene fumerate)-co-(butylene maleate) (PBFcBM) have been synthesized from the ring opening and condensation reactions of maleic anhydride (MA) and 1,3-butanediol (BD). PBFcBM synthesized in this way contains greater than 85% maleate groups. Both PBF and PBFcBM have a glass transition temperature (Tg) below room temperature and therefore cannot be electrospun using the conventional electrospinning process as a non-porous film results. To facilitate production of nonwoven micro- and nano-fiber mats, a UV-source (λ=356 nm) was used in combination with a photoinitator loaded polymer solution to initiate the crosslinking reaction of the fumerate and maleate functional groups as the fibers were produced. The resulting non-woven fiber mats are potentially suitable scaffolds for tissue engineering and drug delivery application.

A wide variety of nanofillers of varying compositions have been used to create polymer nanocomposites, including tubes, wires, fibers, sheets, and particles. A new class of compounds has been identified for use as nanofillers, boron cage compounds. Boron cage compounds are discrete, icosahedral closed cage molecules of high boron content and examples include carboranes and dodecaborate salts. Several chemically modified boron cage compounds have been incorporated into polyolefin elastomers, such as poly(ethylene-co-vinyl acetate), poly(ethylene-co-vinyl acetate-co-vinyl alcohol), poly(ethylene-co-ethyl acrylate), and poly(ethylene-co-octene), among others. The resulting thermal and thermomechanical properties were evaluated in order to determine when plasticization and reinforcement occur to better understand the chemical structure/physical property relationships. Materials with a wide range of properties were produced, however under certain conditions, advanced materials were created with high boron contents, improved thermal stability, mechanical strength, and significant reinforcement.

This paper presents a combined experimental and theoretical/computational study of adhesion and interfacial fracture between multilayers in a CYPHER® model drug eluting stents (DES). Atomic Force Microscopy (AFM) is used to obtain pull-off forces between coated AFM tips and substrates that simulate the bimaterial surfaces in the DES. Adhesion theories and fracture mechanics concepts are then applied to obtain estimates of the fracture toughness over a range of mode mixities between pure mode I and pure mode II. The trends in the estimates are shown to be in good agreement with experimental measurements of interfacial fracture toughness obtained from Brazil disk specimens over the same range of mode mixities.

In this investigation, an apatite/collagen composite coating was formed at 37C on a NiTi shape memory alloy (SMA) through electrochemical deposition using double-strength simulated body fluid (2SBF) which contained dissolved collagen. Surface characteristics, wettability and stability of the composite coating were subsequently studied. Scanning electron microscope (SEM) examination of the surface of composite coatings revealed that many collagen fibers were embedded in apatite with flake-like structure and apatite nanocrystals nucleated and grew on collagen fibrils. Energy dispersive X-ray (EDX) spectroscopy analysis showed that the Ca : P ratio of the composite coating was about 1.35, which is close to that of octocalcium phosphate. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) analysis were also conducted for the composite coating. Compared to bare NiTi SMA samples, the potentiodynamic polarization curves of NiTi SMA samples with the composite coating displayed lower corrosion current density, more positive corrosion and breakdown potential, suggesting that the composite coating was chemically stable and provided corrosion resistance for NiTi SMA.

High molecular weight vinyl esters and carbonates based on oligo(ethylene glycol), oligomeric fatty acids and poly(hexamethylene carbonate), as alternatives for potentially cytotoxic acrylate based monomers have been structured by Additive Manufacturing Technologies (AMTs) like Microstereolithography (μ-SLA), Digital Light Processing (DLP) and Two-Photon Induced Photopolymerization (TPIP). With these techniques feature resolutions down to 10 μm (μ-SLA and DLP) or even 200 nm (TPIP) can be obtained. This new class of monomers exhibits LC50 values for cytotoxicity up to two orders of magnitude lower than acrylate references. Beside a high reactivity of the resin, the shrinkage and the mechanical properties of the final part material are another essential parameter. Low molecular weight monomers are very reactive and lead to densely cross-linked materials which suffer from high shrinkage and strains within the cured material. Therefore, mixtures of high molecular weight vinyl esters/carbonates with low molecular weight crosslinkers have been evaluated regarding their photoreactivity and mechanical properties.

A compact and uniform (Ti, Si, O, N)/Ti composite coating was fabricated on the surface of a NiTi shape memory alloy (SMA) (containing 50.8 at.% Ni) using plasma immersion ion implantation and deposition (PIIID) with radio-frequency (RF) magnetron sputtering. The coating and coated NiTi SMA were studied using various techniques. Analysis showed that the Ni content was drastically reduced on the surface of coated samples due to coating formation. This could greatly improve the biocompatibility of NiTi SMA. There was no TiO2 or TiN formation in the coating. The shape memory ability of NiTi SMA samples was no deteriorated by the coating process. The coating significantly improved the corrosion resistance and wear resistance of NiTi SMA and also rendered the material bioactive.

Hydroxyapatite (HA) nanospheres were synthesized via the sol-gel route in the presence of poly(vinyl alcohol) (PVA). The HA nanospheres were formed from the reaction between (NH4)2HPO4 and CaCl2 in ethanol/PVA sol-gel system, in which ammonia solution (NH3•H2O) was added to adjust the pH of solution. The as-synthesized products were characterized by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), field emission scanning electron microscopy (FE-SEM) and energy-dispersive X-ray spectroscopy (EDAX). XRD patterns and FTIR spectra showed that the HA nanospheres exhibit the crystalline structure and vibration bands of HA. The Ca/P molar ratio of HA nanospheres (50˜70nm) approached the stoichiometric value of 1.67, on the basis of EDAX results. Simulated Body Fluid (SBF) immersion test for three weeks demonstrated that the apatite layer can be formed on the HA nanospheres sintered at 550°C.

Cell encapsulation has been broadly investigated as a technology to provide immunoprotection for transplanted endocrine cells. Here we develop a new fabrication method that allows for rapid, homogenous microencapsulation of insulin-secreting cells with varying microscale geometries and asymmetrically modified surfaces. Micromolding systems were developed using polypropylene mesh, and the mesh material/surface properties associated with efficient encapsulation were identified. Cells encapsulated using these methods maintain desirable viability and preserve their ability to proliferate and secrete insulin in a glucose-responsive manner. This new cell encapsulation approach enables a practical route to an inexpensive and convenient process for the generation of cell-laden microcapsules without requiring any specialized equipment or microfabrication process.

Seeding a layer of cells at specific depths within scaffolds is an important optimization parameter for bi-layer skin models. The work presented investigated the effect of fiber diameter and its mechanical property on the depth of cell seeding for electro-spun fiber scaffold. Polycaprolactone (PCL) is used to generate scaffolds that are submicron (400nm) to micron (1100nm) using electro-spinning. 3T3 fibroblasts were seeded on the electro-spun fiber scaffold mat of 50-70 microns thickness in this study. In order to investigate the effect of fiber diameter on cell migration, first, the electrospun fiber scaffold was studied for variation of mechanical properties as a function of fiber diameters. Atomic force microscopy (AFM) was used to investigate the Young’s modulus (E) values as a function of fiber diameter. It was identified that as the fiber diameter increases, the Young’s modulus values decreases considerably from 1.1GPa to 200MPa. The variation in E is correlated with cell seeding depth as a function of vacuum pressure. A higher E value led to a lower depth of cell seeding (closer to the surface) indicating that nanofibrous scaffolds offer larger resistance to cell movement compared to microfibrous scaffolds.

Bio-electrospraying and aerodynamically assisted bio-jetting are rapidly evolving approaches for directly handling living cells and organisms. In this article we demonstrate how these technologies now elucidated as being safe for handling living cells and organisms can be explored not only for tissue engineering and regenerative medicine but also in biology for single cell and organism diagnostics.

Electric Cell-Impedance Sensing (ECIS) is a real-time transduction system that can be used to detect the presence of foreign particles or pathogens by measuring the changes in impedance or resistance of a cell monolayer grown on an electrode. Herein, we present the use of ECIS for the detection of the toxicity of silver nanoparticles on Madine Derby Canine Kidney (MDCK) epithelial cells as a function of changes in the cell confluence and barrier function of the cell monolayer. The barrier function is a measure of the number of tight junctions formed between confluent cells in a monolayer; tighter confluence leads to an increase in a barrier function and thus in the measured resistance. We were able to detect exposures as low as 1 μg of 20 nm silver nanoparticles per 105 cells within 2 hours; those exposures were quantified as a significant drop in impedance and a gradual decrease in the barrier function as compared to the controls. Future work would include the detection of protein toxins using impedance sensing as well as further analysis of the barrier function using fluorescent staining.

The extracellular matrix plays a crucial role in defining the mechanical properties of connective tissues like cornea, heart, tendon, bone and cartilage among many others. The unique properties of these collagenous tissues arise because of both the hierarchal structure of collagens and the presence of negatively charged proteoglycans (PGs) which hold collagen fibers together. Here, in an effort to understand the mechanics of these structures, using the nonlinear Poison-Boltzmann (PB) equation, we study the electrostatic contribution to the elasticity of corneal stroma due to the presence of negatively charged PG glycosminoglycans (GAGs). Since collagens and GAGs have a regular hexagonal arrangement inside the corneal stroma, a triangular unit cell is chosen. The finite element method is used to solve the PB equation inside this domain and to obtain the electric potential and ionic distributions. Having the ion and potential distributions throughout the unit cell, the electrostatic free energy is computed and the tissue elasticity is calculated using the energy method. It is shown that as the ionic bath concentration increases; the electrostatic contribution to tissue elasticity is reduced.

Biomimetics deals with the application of nature-made ‘design solutions’ to the realm of engineering. In the quest to understand mechanical implications of structural hierarchies found in biological materials, multiscale mechanics may hold the key to understand ‘building plans’ inherent to entire material classes, here bone and bone replacement materials. Analyzing a multitude of biophysical hierarchical and biomechanical experiments through homogenization theories for upscaling stiffness and strength properties, reveals the following design principles: The elementary component ‘collagen’ induces, right at the nanolevel, the mechanical anisotropy of bone materials, which is amplified by fibrillar collagen-based structures at the 100 nm-scale, and by pores in the micrometer-to-millimeter regime. Hydroxyapatite minerals are poorly organized, and provide stiffness and strength in a quasi-brittle manner. Water layers between hydroxyapatite crystals govern the inelastic behavior of the nano-composite, unless the ‘collagen reinforcement’ breaks. Bone replacement materials should mimic these ‘microstructural mechanics’-features as closely as possible.

PLLA microparticles were successfully fabricated via pulsed-DC electrospray. In this study, we investigated the effect of the pulsed voltage characteristics (e.g. pulse frequency, pulse amplitude and pulse width) on the particle’s size. We found that pulse frequency, pulse amplitude, pulse width, and the combinations of these factors had a statistically significant effect on the particle’s size. The process conditions to obtain smaller particles with uniform shape and size are a low pulse frequency, high pulse amplitude, and long pulse width (or a high duty cycle).

The mechanical properties of materials designated for vascular tissue replacement are of crucial importance. The elastic modulus, the tensile strength as well as the suture tear resistance have to be adjusted. Our approach is to use photopolymers for artificial vascular grafts. Via the layer-by-layer photopolymerization of suitable resin formulations as performed in additive manufacturing (AM) very complex structures are realizable. Hence AM offer the possibility to create cellular structures within the artificial grafts that might favor the ingrowth of new tissue. Commercially available urethane acrylates (UA) were chosen as base monomers since urethane groups are known to have good cell-adhesion behavior and poly-UAs show adequate mechanical performance. The mechanical properties of the photoelastomers can be tailored by addition of reactive diluents (e.g. 2-hydroxyethyl acrylate, HEA) and thiols (e.g. 3,6 dioxa-1,8-octane-dithiol) as chain transfer agents to comply with the mechanical properties of natural blood vessels. To examine the suture tear resistance a new testing method has been developed. Finally, a formulation containing 30 wt% UA and 70 wt% HEA complies with the mechanical properties of natural blood vessels, shows good biocompatibility in in-vitro tests and was successfully 3D-printed with digital light processing AM.

We report the structural transformation and the transport studies of Silver doped hydroxyapatites Ca10-xAgx(PO4)6(OH)2 (0.0 ≤ x ≤ 1.5). A dramatic increase in the conductivity by two orders of magnitude for hydroxyapatite in presence of silver ions is recorded using impedance spectroscopy measurements in the temperature range of 450°C to 650°C. The characteristic surface plasmon resonance effect is used to explore the presence of silver nano-particles, and Ag+ ions in hydroxyapatite using optical absorption measurements. The activation energy has been found to be 0.07 eV in silver doped composition in comparison to 0.39 eV for the parent hydroxyapatite. The sintering temperature dependence and compositional variation on the structural transformations from hydroxyapatite into tricalcium phosphate phases have been explored using Raman Spectroscopy and X-ray diffraction techniques.