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Finite element modelling and design of a concentration gradient generating bioreactor: Application to biological pattern formation and toxicology

TitleFinite element modelling and design of a concentration gradient generating bioreactor: Application to biological pattern formation and toxicology
Publication TypeJournal Article
Year of Publication2010
AuthorsVozzi, G, Mazzei, D, Tirella, A, Vozzi, F, Ahluwalia, A
JournalToxicology in vitro
Volume24
Pagination1828–1837
ISSN1879-3177
KeywordsBioengineering
Abstract

This paper describes the use of a microfluidic gradient maker for the toxicological analysis of some conventional biomolecules such as hydrogen peroxide and a local anaesthetic, lidocaine on different cell cultures, human endothelial cells and myoblasts, respectively. The microfluidic device was designed and simulated using COMSOL Multiphysics(R) and the concentration gradient in the microfluidic network was analysed through a fluid-dynamic and mass-transport study. Subsequently the device was fabricated with soft lithography, casting PDMS in a master to obtain channels about 250mum deep. Hydrogen peroxide was tested on human endothelial cells, while lidocaine was tested on C2C12 myoblasts and an analysis was performed using propidium iodide staining followed by an imaging processing routine to obtain quantitative dose-response profiles in the gradient maker. The results show that the Gradient Maker (GM) bioreactor is a more sensitive method for detection of cell toxicity, and compared with testing of drug toxicity using microwells with individual cell cultures, allows one shot testing with a single cell culture exposed to a large number of concentrations. Moreover, the Gradient Maker was also modelled in order to realise biological pattern formation using two morphogenes acting as activator and inhibitor with varying diffusion rates.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/20580814
DOI10.1016/j.tiv.2010.05.010

The impact of fabrication parameters and substrate stiffness in direct writing of living constructs

TitleThe impact of fabrication parameters and substrate stiffness in direct writing of living constructs
Publication TypeJournal Article
Year of Publication2012
AuthorsTirella, A, Ahluwalia, A
JournalBiotechnology progress
Volume28
Pagination1315–1320
ISSN1520-6033
KeywordsBioengineering
Abstract

Biomolecules and living cells can be printed in high-resolution patterns to fabricate living constructs for tissue engineering. To evaluate the impact of processing cells with rapid prototyping (RP) methods, we modeled the printing phase of two RP systems that use biomaterial inks containing living cells: a high-resolution inkjet system (BioJet) and a lower-resolution nozzle-based contact printing system (PAM(2) ). In the first fabrication method, we reasoned that cell damage occurs principally during drop collision on the printing surface, in the second we hypothesize that shear stresses act on cells during extrusion (within the printing nozzle). The two cases were modeled changing the printing conditions: biomaterial substrate stiffness and volumetric flow rate, respectively, in BioJet and PAM(2) . Results show that during inkjet printing impact energies of about 10(-8) J are transmitted to cells, whereas extrusion energies of the order of 10(-11) J are exerted in direct printing. Viability tests of printed cells can be related to those numerical simulations, suggesting a threshold energy of 10(-9) J to avoid permanent cell damage. To obtain well-defined living constructs, a combination of these methods is proposed for the fabrication of scaffolds with controlled 3D architecture and spatial distribution of biomolecules and cells. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/22736619
DOI10.1002/btpr.1586

A phase diagram for microfabrication of geometrically controlled hydrogel scaffolds

TitleA phase diagram for microfabrication of geometrically controlled hydrogel scaffolds
Publication TypeJournal Article
Year of Publication2009
AuthorsTirella, A, Orsini, A, Vozzi, G, Ahluwalia, A
JournalBiofabrication
Volume1
Pagination045002
ISSN1758-5090
KeywordsBioengineering
Abstract

Hydrogels are considered as excellent candidates for tissue substitutes by virtue of their high water content and biphasic nature. However, the fact that they are soft, wet and floppy renders them difficult to process and use as custom-designed scaffolds. To address this problem alginate hydrogels were modeled and characterized by measuring stress-strain and creep behavior as well as viscosity as a function of sodium alginate concentration, cross-linking time and calcium ion concentration. The gels were then microfabricated into scaffolds using the pressure-assisted microsyringe. The mechanical and viscous characteristics were used to generate a processing window in the form of a phase diagram which describes the fidelity of the scaffolds as a function of the material and machine parameters. The approach can be applied to a variety of microfabrication methods and biomaterials in order to design well-controlled custom scaffolds.

URLhttp://www.ncbi.nlm.nih.gov/pubmed/20811111
DOI10.1088/1758-5082/1/4/045002

Riboflavin and collagen: New crosslinking methods to tailor the stiffness of hydrogels

TitleRiboflavin and collagen: New crosslinking methods to tailor the stiffness of hydrogels
Publication TypeJournal Article
Year of Publication2012
AuthorsTirella, A, Liberto, T, Ahluwalia, A
JournalMaterials Letters
Volume74
Pagination58–61
ISSN0167577X
KeywordsBioengineering
Abstract

Fabricating materials with tailored mechanical properties is a challenge and crucial for their successful application in a variety of fields such as tissue engineering. Here collagen and riboflavin were used to create hydrogels with controlled mechanical properties mimicking those of soft tissues (e.g. liver). Collagen-based hydrogels were obtained using a two-step gelation method. Firstly a physical gelation step (i.e. modulation of temperature and pH) was used to fix a specific shape; then photo-initiated cross-links were formed to increase the stiffness. Specifically the chemical cross-linking step was initiated with UV (ultra-violet) radiation to obtain riboflavin derivatised radical polymerization of collagen chains. Cylindrical shaped samples with controlled dimensions were fabricated, and then tested using compressive loading. We show that the compressive elastic modulus of collagen-based hydrogels can be tuned between 0.9 and 3.6 kPa by changing collagen concentration, irradiation with UV in the presence of riboflavin and freeze-drying.

URLhttp://dx.doi.org/10.1016/j.matlet.2012.01.036
DOI10.1016/j.matlet.2012.01.036

Underwater vehicle technology in the European research project VENUS

TitleUnderwater vehicle technology in the European research project VENUS
Publication TypeJournal Article
Year of Publication2009
AuthorsConte, G, Gambella, L, Scaradozzi, D, Zanoli, SM, Caiti, A, Calabrò, V, Alcocer, A, Alves, J, Cardeira, B, Cunha, R, Curado, F, Oliveira, P, Oliveira, A, Pascoal, A, Rufino, M, Sebastião, L, Silvestre, C
JournalUNDERWATER TECHNOLOGY
Volume28
Pagination175–185
ISSN1756-0543
KeywordsRobotics
URLhttp://dx.medra.org/10.3723/ut.28.175
DOI10.3723/ut.28.175

A geographical information system (GIS)-based simulation tool to assess civilian harbor protection levels

TitleA geographical information system (GIS)-based simulation tool to assess civilian harbor protection levels
Publication TypeJournal Article
Year of Publication2012
AuthorsCaiti, A, Munafò, A, Vettori, G
JournalIEEE JOURNAL OF OCEANIC ENGINEERING
Volume37
Pagination85–102
ISSN0364-9059
KeywordsRobotics
URLhttp://dx.medra.org/10.1109/JOE.2011.2174675
DOI10.1109/JOE.2011.2174675
Refereed DesignationRefereed

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