Meir Israelowitz

Fluid Dynamics in Bioreactor Design: Considerations for the Theoretical and Practical Approach

The following chapter summarizes principles of fluid dynamics in bioreactor design with a focus on mammalian cell-culture systems.

A Differential Pressure Laminar Flow Reactor Supports Osteogenic Differentiation and Extracellular Matrix Formation from Adipose Mesenchymal Stem Cells in a Macroporous Ceramic Scaffold

Abstract We present a laminar flow reactor for bone tissue engineering that was developed based on a computational fluid dynamics model. The bioreactor design permits a laminar flow field through its specific internal shape. An integrated bypass system that prevents pressure build-up through bypass openings for pressure release allows for a constant pressure environment during the changing of permeability values that are caused by cellular growth within a porous scaffold. A macroporous ceramic scaffold, composed of zirconium dioxide, was used as a test biomaterial that studies adipose stem cell behavior within a controlled three-dimensional (3D) flow and pressure environment. The topographic structure of the material provided a basis for stem cell proliferation and differentiation toward the osteogenic lineage. Dynamic culture conditions in the bioreactor supported cell viability during long-term culture and induced cell cluster formation and extra-cellular matrix deposition within the porous scaffold, though no complete closure of the pores with new-formed tissue was observed. We postulate that our system is suitable for studying fluid shear stress effects on stem cell proliferation and differentiation toward bone formation in tissue-engineered 3D constructs.

Development of a Laminar Flow Bioreactor by Computational Fluid Dynamics

The purpose of this study is to improve the design of a bioreactor for growing bone and other three-dimensional tissues using a computational fluid dynamics (CFD) software to simulate flow through a porous scaffold, and to recommend design changes based on the results. Basic requirements for CFD modeling were that the flow in the reactor should be laminar and any flow stagnation should be avoided in order to support cellular growth within the scaffold. We simulated three different designs with different permeability values of the scaffold and tissue. Model simulation addressed flow patterns in combination with pressure distribution within the bioreactor. Pressure build-up and turbulent flow within the reactor was solved by introduction of an integrated bypass system for pressure release. The use of CFD afforded direct feedback to optimize the bioreactor design.

Mechanism of Infrared Detection and Transduction by Beetle Melanophila Acuminata In memory of Jerry Wolken

The Melanophila acuminata beetle is attracted to forest fires via a pair of infrared sensory organs composed of sensilla. Our histological work showed that each sensillum contains lipid layers surrounding a protein layer and a unique polysaccharide base that is associated with a neuron to each sensillum. Infrared microscopy showed that the protein region maximally absorbs infrared radiation at 3 μm wavelength and at 10 μm, which corresponds to the known radiation produced by forest fires at 3 μm. Mathematical calculations showed that the physical properties of the sensilla are such that the expected temperature rise is insufficient for transduction of the infrared signal through mechanical means or as a thermal receptor as previously thought; hence the protein plays the pivotal role in perception of single photons and transmission of the signal within the sensilla.

Three-Dimensional Modelling inside a Differential Pressure Laminar Flow Bioreactor Filled with Porous Media

A three-dimensional computational fluid dynamics- (CFD-) model based on a differential pressure laminar flow bioreactor prototype was developed to further examine performance under changing culture conditions. Cell growth inside scaffolds was simulated by decreasing intrinsic permeability values and led to pressure build-up in the upper culture chamber. Pressure release by an integrated bypass system allowed continuation of culture. The specific shape of the bioreactor culture vessel supported a homogenous flow profile and mass flux at the scaffold level at various scaffold permeabilities. Experimental data showed an increase in oxygen concentration measured inside a collagen scaffold seeded with human mesenchymal stem cells when cultured in the perfusion bioreactor after 24 h compared to static culture in a Petri dish (dynamic: 11% O2 versus static: 3% O2). Computational fluid simulation can support design of bioreactor systems for tissue engineering application.

Biomimetic-Inspired Infrared Sensors from Microwires: Study of Their Photoconductivity and Infrared Spectrum Properties

The fire beetle, Melanophila acuminata (Coleoptera: Buprestidae), senses infrared radiation at wavelengths of 3 and 10–25 microns via specialized protein-containing sensilla. Although the protein denatures outside of a biological system, this detection mechanism has inspired our bottom-up approach to produce single zinc phosphide microwires via vapour transport for IR sensing. The Zn3P2 microwires were immobilized and electrical contact was made by dielectrophoresis. Photoconductivity measurements have been extended to the near IR range, spanning the Zn3P2 band gaps. Purity and integrity of the Zn3P2 microwires including infrared light scattering properties were confirmed by infrared transmission microscopy. This biomimetic microwire shows promise for infrared chip development.

Protein Modelling and Surface Folding by Limiting the Degrees of Freedom

One aspect of tissue engineering represents modelling of the extracellular matrix of connective tissue as the fiber network arrangement of the matrix determines its tensile strength. In order to define the correct position of the e.g. collagen in a structure, an optimized tertiary structure must be characterized. Existing approaches of protein models consider random packing of rigid spheres. We propose an alternative strategy to model protein structure by focusing on the folding. Our model considers (a) segments of amino-acid peptides or beads, (b) hydrogen bond distances, and (c) the distance geometry as functional components rather than minimizing distances between the centers of atoms. We reduced the molecular volume by using concepts from low dimensional topology, such as braids and surfaces, via differential geometry. A braid group maintains the continuity of a sequence while the spatial minimization is performed, and guarantees the continuity during the process. We have applied this approach to different examples of known protein sequences using ab initio protocols of ProteoRubix Systems™. Sequence files of three different proteins types were tested and modeled by ProteoRubix™ and compared to models derived by other methods. ProteoRubix™ created near-identical models with minimal computational load. This model can be expanded to large, multi-molecular network structures.