Colloidal Nano-apatite Particles with Active Luminescent and Magentic Properties for Biotechnology Applications

Colloidal Nano-apatite Particles with Active Luminescent and Magentic Properties for Biotechnology Applications. The synthesis of functional nano-materials is a burgeoning field that has produced remarkable and consistent breakthroughs over the last two decades. Individual particles have become smaller and shown potential for well defined functionality. However, there are still unresolved problems, a primary one being the loss of functionality and novelty due to uncontrolled aggregation driven by surface energy considerations. As such the first design criteria to harness the true potential of nanoparticles is to prevent unwanted agglomeration by: (1) improving, and, if possible, (2) controlling aggregation behavior. This requires specific knowledge of the chemistry of the immediate locale of the intended application; especially for biologically relevant applications. The latter criterion is also application driven but should be considered, generally, to diversify the range of functional properties that can be achieved. We have now reason to believe that such a novel system with multifunctional capabilities can be synthesized rather conveniently and have far reaching impact in biotechnology and other applications in the near future. We are presently experimenting with the syntheses of spheroidal, metal-doped, colloidal apatite nano-particles (~10 nm) for several potential biomedical applications.

Micro- and nanostructured polymer substrates for biomedical applications

Polymer implants are interesting alternatives to the contemporary load-bearing implants made from metals. Polyetheretherketone (PEEK), a well-established biomaterial for example, is not only iso-elastic to bone but also permits investigating the surrounding soft tissues using magnetic resonance imaging or computed tomography, which is particularly important for cancer patients. The commercially available PEEK bone implants, however, require costly coatings, which restricts their usage. As an alternative to coatings, plasma activation can be applied. The present paper shows the plasma-induced preparation of nanostructures on polymer films and on injection-molded micro-cantilever arrays and the associated chemical modifications of the surface. In vitro cell experiments indicate the suitability of the activation process. In addition, we show that microstructures such as micro-grooves 1 μm deep and 20 μm wide cause cell alignment. The combination of micro-injection molding, simultaneous microstructuring using inserts/bioreplica and plasma treatments permits the preparation of polymer implants with nature-analogue, anisotropic micro- and nanostructures.

The Threads of Biosystems Engineering

The core concepts, or threads, of Biosystems Engineering (BSEN) are variously understood by those within the discipline, but have never been unequivocally defined due to its early stage of development. This makes communication and teaching difficult compared to other well established engineering subjects. Biosystems Engineering is a field of Engineering which int egrates engineering science and design with applied biological, environmental and agricultural sciences. It represents an evolution of the Agricultural Engineering discipline applied to all living organisms not including biomedical applications. The basic key element for the emerging EU Biosystems Engineering program of studies is to ensure that it offers essential minimum fundamental engine ering knowledge and competences . A core curriculum developed by Erasmus Thematic Networks is used as benchmark for Agr icultural and Biosystems Engineering studies in Europe. The common basis of the core curriculum for the discipline across the Atlantic , including a minimum of competences comprising the Biosystems Engineering core competencies, has been defined by an Atlan tis project , but this needs to be taken further by defining the threads linking courses together. This paper presents a structured approach to define the Threads of BSEN . The definition of the mid-level competences and the associated learning outcomes has been one of the objectives of the Atlantis programme TABE.NET. The mid-level competences and learning outcomes for each of six specializations of BSEN are defined while the domain-specific knowledge to be acquired for each outcome is proposed. Once the proposed definitions are adopted, these threads will be available for global development of the BSEN.

Thermoelectric assessment of laser peening induced effects on a metallic biomedical Ti6Al4V

Laser peening has recently emerged as a useful technique to overcome detrimental effects associated to another well-known surface modification processes such as shot peening or grit blasting used in the biomedical field. It is worth to notice that besides the primary residual stress effect, thermally induced effects might also cause subtle surface and subsurface microstructural changes that might influence corrosion resistance. Moreover, since maximum loads use to occur at the surface, they could also play a critical role in the fatigue strength. In this work, plates of Ti-6Al-4V alloy of 7 mm in thickness were modified by laser peening without using a sacrificial outer layer. Irradiation by a Q-switched Nd-YAG laser (9.4 ns pulse length) working in fundamental harmonic at 2.8 J/pulse and with water as confining medium was used. Laser pulses with a 1.5 mm diameter at an equivalent overlapping density (EOD) of 5000 cm-2 were applied. Attempts to analyze the global induced effects after laser peening were addressed by using the contacting and non-contacting thermoelectric power (TEP) techniques. It was demonstrated that the thermoelectric method is entirely insensitive to surface topography while it is uniquely sensitive to subtle variations in thermoelectric properties, which are associated with the different material effects induced by different surface modification treatments. These results indicate that the stress-dependence of the thermoelectric power in metals produces sufficient contrast to detect and quantitatively characterize regions under compressive residual stress based on their thermoelectric power contrast with respect to the surrounding intact material. However, further research is needed to better separate residual stress effects from secondary material effects, especially in the case of low-conductivity engineering materials like titanium alloys.

Hydrodynamic evaluation of kangaroo aortic valve matrices for tissue valve engineering

We evaluated the hydrodynamic performance of kangaroo aortic valve matrices (KMs) (19, 21, and 23 mm), as potential scaffolds in tissue valve engineering using a pulsatile left heart model at low and high cardiac outputs (COs) and heart rates (HRs) of 60 and 90 beats/min. Data were measured in two samples of each type, pooled in two CO levels (2.1 +/- 0.7 and 4.2 +/- 0.6 L/min; mean +/- standard errors on the mean), and analyzed using analysis of variance with CO level, HR, and valve type as fixed factors and compared to similar porcine matrices (PMs). Transvalvular pressure gradient (Delta P) was a function of HR (P < 0.001) and CO (P < 0.001) but not of valve type (P = 0.39). Delta P was consistently lower in KMs but not significantly different from PMs. The effective orifice area and performance index of kangaroo matrices was statistically larger for all sizes at both COs and HRs.

Systematic selection of solvents for the fabrication of 3D combined macro- and microporous polymeric scaffolds for soft tissue engineering

In this study, we investigate the fabrication of 3D porous poly(lactic-co-glycolic acid) (PLGA) scaffolds using the thermally-induced phase separation technique. The current study focuses on the selection of alternative solvents for this process using a number of criteria, including predicted solubility. toxicity, removability and processability. Solvents were removed via either vacuum freeze-drying or leaching, depending on their physical properties. The residual solvent was tested using gas chromatography-mass spectrometry. A large range of porous, highly interconnected scaffold architectures with tunable pore size and alignment was obtained, including combined macro- and microporous structures and an entirely novel 'porous-fibre' structure. The morphological features of the most promising poly(lactic-co-glycolic acid) scaffolds were analysed via scanning electron microscopy and X-ray micro-computed tomography in both two and three dimensions. The Young's moduli of the scaffolds under conditions of temperature, pH and ionic strength similar to those found in the body were tested and were found to be highly dependent on the architectures.

Nanopatterned UV curable hydrogels for biomedical applications

With an increasing use of emerging patterning technologies such as UV-NIL in biotechnological applications there is at the same time a raising demand for new material for such applications. Here we present a PEG based precursor mixed with a photoinitiator to make it UV sensitive as a new material aimed at biotechnological applications. Using HSQ patterned quartz stamps we observed excellent pattern replication indicating good flow properties of the resist. We were able to obtain imprints with <20 nm residual layer. The PEG based resist has hydrogel properties and it swelling in water was observed by AFM.

Classification of Biomedical Signals using the Dynamics of the False Nearest Neighbours (DFNN) Algorithm

* This study was supported in part by the Natural Sciences and Engineering Research Council of Canada, and by the Gastrointestinal Motility Laboratory (University of Alberta Hospitals) in Edmonton, Alberta, Canada.

Design and performance assessment of aortic heart valve for tissue engineering

Current artificial heart valves are classified as mechanical and bioprosthetic. An appealing pathway that promises to overcome the shortcomings of commercially available heart valves is offered by the interdisciplinary approach of cardiovascular tissue engineering. However, the mechanical properties of the Tissue Engineering Heart Valves (TEHV) are limited and generally fail in the long-term use. To meet this performance challenge novel biodegradable triblock copolymer poly(ethylene oxide)-polypropylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO or F108) crosslinked to Silk Fibroin (F108-SilkC) to be used as tri-leaflet heart valve material was investigated. ^ Synthesis of ten polymers with varying concentration and thickness (55 µm, 75 µm and 100 µm) was achieved via a covalent crosslinking scheme using bifunctional polyethylene glycol diglycidyl ether (PEGDE). Static and fatigue testing were used to assess mechanical properties of films, and hydrodynamic testing was performed to determine performance under a simulated left ventricular flow regime. The crosslinked copolymer (F108-Silk C) showed greater flexibility and resilience, but inferior ultimate tensile strength, by increasing concentration of PEGDE. Concentration molar ratio of 80:1 (F108: Silk) and thickness of 75 µm showed longer fatigue life for both tension-tension and bending fatigue tests. Four valves out of twelve designed satisfactorily complied with minimum performance requirement ISO 5840, 2005. ^ In conclusion, it was demonstrated that the applicability of a degradable polymer in conjugation with silk fibroin for tissue engineering cardiovascular use, specifically for aortic valve leaflet design, met the performance demands. Thinner thicknesses (t<75 µm) in conjunction with stiffness lower than 320 MPa (80:1, F108: Silk) are essential for the correct functionality of proposed heart valve biomaterial F108-SilkC. Fatigue tests were demonstrated to be a useful tool to characterize biomaterials that undergo cyclic loading. ^

Vacuum brazing of alumina ceramic to titanium for biomedical implants using pure gold as the filler metal

One of the many promising applications of metal/ceramic joining is in biomedical implantable devices. This work is focused on vacuum brazing of C.P titanium to 96% alumina ceramic using pure gold as the filler metal. A novel method of brazing is developed where resistance heating of C.P titanium is done inside a thermal evaporator using a Ta heating electrode. The design of electrode is optimized using Ansys resistive heating simulations. The materials chosen in this study are biocompatible and have prior history in implantable devices approved by FDA. This research is part of Boston Retinal implant project to make a biocompatible implantable device (www.bostonretina.org). ^ Pure gold braze has been used in the construction of single terminal feedthrough in low density hermetic packages utilizing a single platinum pin brazed to an alumina or sapphire ceramic donut (brazed to a titanium case or ferrule for many years in implantable pacemakers. Pure gold (99.99%) brazing of 96% alumina ceramic with CP titanium has been performed and evaluated in this dissertation. Brazing has been done by using electrical resistance heating. The 96% alumina ceramic disk was manufactured by high temperature cofired ceramic (HTCC) processing while the Ti ferrule and gold performs were purchased from outside. Hermetic joints having leak rate of the order of 1.6 × 10-8 atm-cc/ sec on a helium leak detector were measured. ^ Alumina ceramics made by HTCC processing were centreless grounded utilizing 800 grit diamond wheel to provide a smooth surface for sputtering of a thin film of Nb. Since pure alumina demonstrates no adhesion or wetting to gold, an adhesion layer must be used on the alumina surface. Niobium (Nb), Tantalum (Ta) and Tungsten (W) were chosen for evaluation since all are refractory (less dissolution into molten gold), all form stable oxides (necessary for adhesion to alumina) and all are readily thin film deposited as metals. Wetting studies are also performed to determine the wetting angle of pure gold to Ti, Ta, Nb and W substrates. Nano tribological scratch testing of thin film of Nb (which demonstrated the best wetting properties towards gold) on polished 96% alumina ceramic is performed to determine the adhesion strength of thin film to the substrate. The wetting studies also determined the thickness of the intermetallic compounds layers formed between Ti and gold, reaction microstructure and the dissolution of the metal into the molten gold.^

Poly(3-hydroxyoctanoate), a promising new material for cardiac tissue engineering

Cardiac tissue engineering (CTE) is currently a prime focus of research due to an enormous clinical need. In this work, a novel functional material, Poly(3-hydroxyoctanoate), P(3HO), a medium chain length polyhydroxyalkanoate (PHA), produced using bacterial fermentation, was studied as a new potential material for CTE. Engineered constructs with improved mechanical properties, crucial for supporting the organ during new tissue regeneration, and enhanced surface topography, to allow efficient cell adhesion and proliferation, were fabricated. Our results showed that the mechanical properties of the final patches were close to that of cardiac muscle. Biocompatibility of the P(3HO) neat patches, assessed using Neonatal ventricular rat myocytes (NVRM), showed that the polymer was as good as collagen in terms of cell viability, proliferation and adhesion. Enhanced cell adhesion and proliferation properties were observed when porous and fibrous structures were incorporated to the patches. Also, no deleterious effect was observed on the adults cardiomyocytes’ contraction when cardiomyocytes were seeded on the P(3HO) patches. Hence, P(3HO) based multifunctional cardiac patches are promising constructs for efficient CTE. This work will provide a positive impact on the development of P(3HO) and other PHAs as a novel new family of biodegradable functional materials with huge potential in a range of different biomedical applications, particularly CTE, leading to further interest and exploitation of these materials.

Mechanical properties and cellular response of novel electrospun nanofibers for ligament tissue engineering: Effects of orientation and geometry

Electrospun nanofibers are a promising material for ligamentous tissue engineering, however weak mechanical properties of fibers to date have limited their clinical usage. The goal of this work was to modify electrospun nanofibers to create a robust structure that mimics the complex hierarchy of native tendons and ligaments. The scaffolds that were fabricated in this study consisted of either random or aligned nanofibers in flat sheets or rolled nanofiber bundles that mimic the size scale of fascicle units in primarily tensile load bearing soft musculoskeletal tissues. Altering nanofiber orientation and geometry significantly affected mechanical properties; most notably aligned nanofiber sheets had the greatest modulus; 125% higher than that of random nanofiber sheets; and 45% higher than aligned nanofiber bundles. Modifying aligned nanofiber sheets to form aligned nanofiber bundles also resulted in approximately 107% higher yield stresses and 140% higher yield strains. The mechanical properties of aligned nanofiber bundles were in the range of the mechanical properties of the native ACL: modulus=158±32MPa, yield stress=57±23MPa and yield strain=0.38±0.08. Adipose derived stem cells cultured on all surfaces remained viable and proliferated extensively over a 7 day culture period and cells elongated on nanofiber bundles. The results of the study suggest that aligned nanofiber bundles may be useful for ligament and tendon tissue engineering based on their mechanical properties and ability to support cell adhesion, proliferation, and elongation.