Biomedical subjects

Marcello Lappa

Publications and source records attributed to Marcello Lappa.

5 recordsLinked to original sources

PubMed2005

Discrete layers of interacting growing protein seeds: convective and morphological stages of evolution.

The growth of several macromolecular seeds uniformly distributed on the bottom of a protein reactor (i.e., a discrete layer of N crystals embedded within a horizontal layer of liquid with no-slip boundaries) under microgravity conditions is investigated for different values of N and for two values of the geometrical aspect ratio of the container. The fluid dynamics of the growth reactor and the morphological (shape-change) evolution of the crystals are analyzed by means of a recently developed moving boundary method based on differential equations coming from the protein "surface incorporation kinetics." The face growth rates are found to depend on the complex multicellular structure of the convective field and on associated "pluming phenomena." This correspondence is indirect evidence of the fact that mass transport in the bulk and surface attachment kinetics are competitive as rate-limiting steps for growth. Significant adjustments in the roll pattern take place as time passes. The convective field undergoes an interesting sequence of transitions to different values of the mode and to different numbers of rising solutal jets. The structure of the velocity field and the solutal effects, in turn, exhibit sensitivity to the number of interacting crystals if this number is small. In the opposite case, a certain degree of periodicity can be highlighted for a core zone not affected by edge effects. The results with no-slip lateral walls are compared with those for periodic boundary conditions to assess the role played by geometrical constraints in determining edge effects and the wavelength selection process. The numerical method provides "microscopic" and "morphological" details as well as general rules and trends about the macroscopic evolution (i.e., "ensemble behaviors") of the system.

Binding Sites↗

PubMed2005

A CFD level-set method for soft tissue growth: theory and fundamental equations.

A level-set method, specifically conceived for the case of soft organic tissue growth from feeding solutions, is introduced and described in detail. The model can handle the morphological evolution of the organic specimen under the influence of external convection (fluid-dynamics of the bioreactor). The analogies and differences between this technique and a previous volume of fraction method are discussed pointing out advantages and limitations of both formulations.

Growth↗

PubMed2003

Organic tissues in rotating bioreactors: fluid-mechanical aspects, dynamic growth models, and morphological evolution.

This analysis deals with advances in tissue-engineering models and computational methods as well as with novel results on the relative importance of "controlling forces" in the growth of organic constructs. Specifically, attention is focused on the rotary culture system, because this technique has proven to be the most practical solution for providing a suitable culture environment supporting three-dimensional tissue assemblies. From a numerical point of view, the growing biological specimen gives rise to a moving boundary problem. A "volume-of-fraction" method is specifically and carefully developed according to the complex properties and mechanisms of organic tissue growth and, in particular, taking into account the sensitivity of the construct/liquid interface to the effect of the fluid-dynamic shear stress (it induces changes in tissue metabolism and function that elicit a physiological response from the biological cells). The present study uses available data to introduce a set of growth models. The surface conditions are coupled to the transfer of mass and momentum at the specimen/culture-medium interface and lead to the introduction of a group of differential equations for the nutrient concentration around the sample and for the evolution of tissue mass displacement. The models are then used to show how the proposed surface kinetic laws can predict (through sophisticated numerical simulations) many of the known characteristics of biological tissues grown using rotating-wall perfused vessel bioreactors. This procedure provides a validation of the models and associated numerical method and also gives insight into the mechanisms of the phenomena. The interplay between the increasing size of the tissue and the structure of the convective field is investigated. It is shown that this interaction is essential in determining the time evolution of the tissue shape. The size of the growing specimen plays a critical role with regard to the intensity of convection and the related shear stresses. Convective effects, in turn, are found to impact growth rates, tissue size, and morphology, as well as the mechanisms driving growth. The method exhibits novel capabilities to predict and elucidate experimental observations and to identify cause-and-effect relationships.

Acceleration↗

PubMed2003

The growth and the fluid dynamics of protein crystals and soft organic tissues: models and simulations, similarities and differences.

The fluid-dynamic environment within typical growth reactors as well as the interaction of such flow with the intrinsic kinetics of the growth process are investigated in the frame of the new fields of protein crystal and tissue engineering. The paper uses available data to introduce a set of novel growth models. The surface conditions are coupled to the exchange mass flux at the specimen/culture-medium interface and lead to the introduction of a group of differential equations for the nutrient concentration around the sample and for the evolution of the construct mass displacement. These models take into account the sensitivity of the construct/liquid interface to the level of supersaturation in the case of macromolecular crystal growth and to the "direct" effect of the fluid-dynamic shear stress in the case of biological tissue growth. They then are used to show how the proposed surface kinetic laws can predict (through sophisticated numerical simulations) many of the known characteristics of protein crystals and biological tissues produced using well-known and widely used reactors. This procedure provides validation of the models and associated numerical method and at the same time gives insights into the mechanisms of the phenomena. The onset of morphological instabilities is discussed and investigated in detail. The interplay between the increasing size of the sample and the structure of the convective field established inside the reactor is analysed. It is shown that this interaction is essential in determining the time evolution of the specimen shape. Analogies about growing macromolecular crystals and growing biological tissues are pointed out in terms of behaviours and cause-and-effect relationships. These aspects lead to a common source (in terms of original mathematical models, ideas and results) made available for the scientific community under the optimistic idea that the contacts established between the "two fields of engineering" will develop into an ongoing, mutually beneficial dialogue.

Animals↗

PubMed2002

Experimental observations and numerical modelling of diffusion-driven crystallisation processes.

This paper reports experimental results and modelling on the crystallisation processes induced by counter diffusion method of a precipitant agent in a lysozyme protein solution. Comparison between experimental observations and numerical simulations in the presence of convection and sedimentation and without them (suppressed using gel) provides a validation of the model. Different values of the initial protein concentration are used, in order to investigate the effects of supersaturation conditions on the process, and in particular on nucleation. The model and the experimental approach may represent a useful methodology for the determination of the parameters and conditions that may lead to protein crystallisation. A Mach-Zehnder interferometer is used to monitor the transport dynamics in situ in the fluid phase by observing the compositional field. The effect of the solute transport gives rise to a "nucleation front" that propagates inside the protein solution. The crystal formation, caused by progressing of the front, results in a modulation in time and in space (similar to Liesegang patterns), due to the non-linear interplay among transport, crystal nucleation and growth. Both experimental observation and numerical modelling show spatial and size distributions of crystals that demonstrate comparable evidences of the phenomena.

Animals↗