@article {2510, title = {Decoupling the role of stiffness from other hydroxyapatite signalling cues in periosteal derived stem cell differentiation}, journal = {Scientific Reports}, volume = {5}, year = {2015}, pages = {10778}, keywords = {Bioengineering}, issn = {2045-2322}, doi = {10.1038/srep10778}, url = {http://www.nature.com/doifinder/10.1038/srep10778}, author = {G. Mattei and Ferretti, C. and Tirella, A and A. Ahluwalia and Mattioli-Belmonte, M.} } @article {2507, title = { HisTOOLogy: an open-source tool for quantitative analysis of histological sections }, journal = {Journal of Microscopy}, year = {2015}, month = {08/2015}, keywords = {Bioengineering}, doi = {10.1111/jmi.12292. }, author = {C. Magliaro and Tirella, A and G. Mattei and Pirone, A. and A. Ahluwalia} } @article {2511, title = {Nano-in-Micro Self-Reporting Hydrogel Constructs}, journal = {Journal of Biomedical Nanotechnology}, volume = {11}, year = {2015}, pages = {1451{\textendash}1460}, keywords = {Bioengineering}, issn = {15507033}, doi = {10.1166/jbn.2015.2085}, url = {http://openurl.ingenta.com/content/xref?genre=article\&issn=1550-7033\&volume=11\&issue=8\&spage=1451}, author = {Tirella, A and La Marca, M and Brace, L.A. and G. Mattei and Aylott, J. and A. Ahluwalia} } @article {2274, title = {A novel dual-flow bioreactor simulates increased fluorescein permeability in epithelial tissue barriers}, journal = {Biotechnology journal}, year = {2014}, abstract = {

Permeability studies across epithelial barriers are of primary importance in drug delivery as well as in toxicology. However, traditional in vitro models do not adequately mimic the dynamic environment of physiological barriers. Here, we describe a novel two-chamber modular bioreactor for dynamic in vitro studies of epithelial cells. The fluid dynamic environment of the bioreactor was characterized using computational fluid dynamic models and measurements of pressure gradients for different combinations of flow rates in the apical and basal chambers. Cell culture experiments were then performed with fully differentiated Caco-2 cells as a model of the intestinal epithelium, comparing the effect of media flow applied in the bioreactor with traditional static transwells. The flow increases barrier integrity and tight junction expression of Caco-2 cells with respect to the static controls. Fluorescein permeability increased threefold in the dynamic system, indicating that the stimulus induced by flow increases transport across the barrier, closely mimicking the in vivo situation. The results are of interest for studying the influence of mechanical stimuli on cells, and underline the importance of developing more physiologically relevant in vitro tissue models. The bioreactor can be used to study drug delivery, chemical, or nanomaterial toxicity and to engineer barrier tissues.

}, keywords = {Bioengineering}, issn = {1860-7314}, doi = {10.1002/biot.201400004}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24756869}, author = {S. Giusti and Sbrana, T. and La Marca, M and V. Di Patria and V. Martinucci and Tirella, A and C. Domenici and A. Ahluwalia} } @conference {2275, title = {Sensorized Squeeze Pressure Bioreactor For mechanical modulation of cardiomyocyte phenotype}, booktitle = {Journal of tissue engineering and regenerative medicine}, volume = {8 Suppl 1}, year = {2014}, pages = {67{\textendash}8}, keywords = {Bioengineering}, doi = {10.1002/term.1943}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24912686}, author = {S. Giusti and Vozzi, F. and F. Pagliari and Tirella, A and D. Mazzei and Cabiati, M and S. del Ry and A. Ahluwalia} } @article {2290, title = {Sphyga: a multiparameter open source tool for fabricating smart and tunable hydrogel microbeads}, journal = {Biofabrication}, volume = {6}, year = {2014}, keywords = {Bioengineering}, doi = {10.1088/1758-5082/6/2/025009}, author = {Tirella, A and C. Magliaro and M. Penta and M. Troncone and Pimentel, R and A. Ahluwalia} } @inbook {1787, title = {Da scaffold a tessuti: progettazione, realizzazione e caratterizzazione di architetture 3D per la medicina rigenerativa }, booktitle = {Approccio Integrato per la medicina rigenerativa - book of XXXII School of Bioengineering}, year = {2013}, keywords = {Bioengineering}, author = {Tirella, A and C. De Maria and G. Vozzi and A. Ahluwalia} } @conference {1798, title = {Gelatin-Hydroxyapatite hydrogels to investigate periosteal derived progenitor cells (PDPCs) response for tissue engineering applications}, booktitle = {Advanced Cell Culture}, year = {2013}, address = {Liverpool, UK}, keywords = {Bioengineering}, author = {G. Mattei and Tirella, A and Mattioli-Belmonte, M. and Ferretti, C and A. Ahluwalia} } @article {1791, title = {In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response}, journal = {Nanotoxicology}, year = {2013}, abstract = {

Abstract After passage through biological barriers, nanomaterials inevitably end up in contact with the vascular endothelium and physiological flow, and can induce cardiovascular damage. In this study the toxicity and sublethal effects of 6 nanoparticles, including 4 of industrial and biomedical importance, on human endothelial cells was investigated using different in vitro assays. The results show that all the particles investigated induce some level of damage to the cells and that silver particles were most toxic, followed by titanium dioxide. Furthermore endothelial cells were shown to be more susceptible when exposed to silver nanoparticles under flow conditions in a bioreactor. The study underlines that although simple in vitro tests are useful to screen compounds and to identify the type of effect induced on cells, they may not be sufficient to define safe exposure limits. Therefore, once initial toxicity screening has been conducted on nanomaterials, it is necessary to develop more physiologically relevant in vitro models to better understand how nanomaterials can impact on human health.

}, keywords = {Bioengineering}, issn = {1743-5404}, doi = {10.3109/17435390.2013.831500}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23909703}, author = {Ucciferri, N and Collnot, E. M. and Gaiser, B. and Tirella, A and Stone, V. and C. Domenici and Lehr, C.-M. and A. Ahluwalia} } @conference {1793, title = {{SpHyGa: fabrication of hepatic lobule replicas using tissue derived material composites}}, booktitle = {ESB 2013}, year = {2013}, pages = {ID 520}, address = {Madrid}, keywords = {Bioengineering}, author = {M. La Marca and Tirella, A and G. Mattei and A. Ahluwalia} } @article {2281, title = {SQPR 3.0: A Sensorized Bioreactor for Modulating Cardiac Phenotype}, journal = {Procedia Engineering}, volume = {59}, year = {2013}, pages = {219{\textendash}225}, abstract = {

In cardiac tissue engineering, the use of bioreactors is fundamental for applying controlled mechanical stimuli on cells and recreate a physiological environment for cardiomyocyte cultures. This work is focused on the design of a sensorized Squeeze Pressure bioreactor (SQPR 3.0) able to apply a periodic contactless hydrodynamic pressure on tissue constructs. This system was then tested with H2c9, a murine cardiomyoblast cell line, to investigate the effect of different stimulation times (2h, 24h, 30h) on cell shape and cardiotypic marker expression.

}, keywords = {Bioengineering}, issn = {18777058}, doi = {10.1016/j.proeng.2013.05.114}, url = {http://linkinghub.elsevier.com/retrieve/pii/S187770581301028X}, author = {S. Giusti and F. Pagliari and Vozzi, F. and Tirella, A and D. Mazzei and Cabiati, M and S. del Ry and A. Ahluwalia} } @article {1790, title = {{Strain rate viscoelastic analysis of soft and highly hydrated biomaterials.}}, journal = {Journal of biomedical materials research. Part A}, year = {2013}, abstract = {

Measuring the viscoelastic behaviour of highly hydrated biological materials is challenging because of their intrinsic softness and labile nature. In these materials it is difficult to avoid pre-stress and therefore to establish precise initial stress and strain conditions for lumped parameter estimation using creep or stress-relaxation tests. We describe a method ($ε$M or epsilon dot method) for deriving the viscoelastic parameters of soft hydrated biomaterials which avoids pre-stress and can be used to rapidly test degradable samples. Standard mechanical tests are first performed compressing samples using different strain rates. The dataset obtained is then analysed to mathematically derive the material{\textquoteright}s viscoelastic parameters. In this work a stable elastomer, PDMS, and a labile hydrogel, gelatin, were first tested using the $ε$M, in parallel stress-relaxation was used to compare lumped parameter estimation. After demonstrating that the elastic parameters are equivalent and that the estimation of short time constants is more precise using the proposed method, the viscoelastic behaviour of porcine liver was investigated using this approach. The results show that the constitutive parameters of hepatic tissue can be quickly quantified without the application of any pre-stress and before the onset of time dependent degradation phenomena.

}, keywords = {Bioengineering}, issn = {1552-4965}, doi = {10.1002/jbm.a.34914}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23946054}, author = {Tirella, A and G. Mattei and A. Ahluwalia} } @conference {1802, title = {Towards a controlled and monitorable hepatic micro-environment}, booktitle = {Advanced Cell Culture}, year = {2013}, address = {Liverpool, UK}, keywords = {Bioengineering}, author = {Tirella, A and La Marca, M and Carroll, L. A. and Aylott, J and A. Ahluwalia} } @conference {1801, title = {Continuous functionally graded materials (cFGMs) for TE}, booktitle = {TERMIS 3rd World Congress}, year = {2012}, address = {Vienna, Austria}, abstract = {

Biological structures are not uniform but possess spatially distributed functions and properties, or functional gradients. To ensure functional, mechanical and structural integration, a tissue engineered (TE) scaffold has to reproduce these functional gradients. However the fabrication of functionally graded materials is challenging and usually an experimental trial-and-error approach is used. In this work we present a controlled method for the fabrication of cFGMs using the gravitational sedimentation of discrete solid particles within a primary fluid phase. To have an overall control over particle distribution, a time-varying dynamic viscosity solution (i.e. thermo-sensitive) was used as fluid phase. Computational fluid dynamic models were developed to have a fine control over particle distribution. Biomimetic osteochondral cFGMs scaffolds were fabricated using hydroxyapatite (HA) and gelatin. Glutaraldehyde was used to covalently bind gelatin-HA graded scaffolds. Mechanical properties were measured and correlated as a function of HA volume fraction. SEM-EDX analysis was used to further characterise HA content and its distribution within gelatin-HA cFGMs. Finally gelatin-HA cFGMs scaffold were seeded using periosteum derived progenitor cells, to investigate how the HA gradient modulates cell response. This approach represents an innovative yet simple tool for the fabrication of tailored cFGMs with biologically and physiologically relevant gradients for TE applications.

}, keywords = {Bioengineering}, author = {G. Mattei and A. Ahluwalia and Ferretti, C and Mattioli-Belmonte, M. and Tirella, A} } @article {1330, title = {Functionally Graded Materials (FGMs) with predictable and controlled gradient profiles: computational modelling and realisation}, journal = {International Journal for Computational Methods in Engineering Science \& Mechanics (CMES)}, year = {2012}, pages = {accepted}, keywords = {Bioengineering}, author = {G. Mattei and Tirella, A and A. Ahluwalia} } @article {1329, title = {The impact of fabrication parameters and substrate stiffness in direct writing of living constructs}, journal = {Biotechnology progress}, volume = {28}, year = {2012}, pages = {1315{\textendash}1320}, 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. {\textcopyright} 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012.

}, keywords = {Bioengineering}, issn = {1520-6033}, doi = {10.1002/btpr.1586}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22736619}, author = {Tirella, A and A. Ahluwalia} } @conference {1804, title = {Monitoring cell culture 3D microenvironments: oxygen and pH nano-sensors within hydrogels}, booktitle = {National Conference of Bioengineering}, year = {2012}, address = {Rome, Italy}, abstract = {

Ratiometric pH and O2 nanosensors were fabricated independently using a fluorophore that produces a signal proportional to the concentration of the analyte of interest, and a second fluorophore that produces a reference signal, insensitive to the analyte of interest. These fluorophores emit at different wavelengths and were either entrapped or covalently bound, within an inert optically transparent polymeric matrix. In this work uniform sized 3D micro-scaled alginate hydrogel constructs of approximately 100-300 $μ$m were fabricated. Through dual incorporation of HepG2 cells and nanosensors within these alginate constructs we aim to have a real-time, non-invasive method to measure microenvironmental pH and O2 content. Ratiometric fluorescent output from the microenvironment is used to monitor O2 concentrations and pH during cell culture. Measurements show that 3D micro-scaled constructs are suitable for cell growth and proliferation. Moreover O2 and pH values within the hydrogel cellularised microspheres are shown to have physiological values that enable the maintenance of the hepatic phenotype

}, keywords = {Bioengineering}, author = {Tirella, A and Carroll, L. A. and Aylott, J and A. Ahluwalia} } @conference {1800, title = {{Monitoring microconstructs: cell and nanosensor encapsulation in alginate micro-beads}}, booktitle = {TERMIS 3rd World Congress}, year = {2012}, address = {Vienna, Austria}, abstract = {

Monitoring and controlling the microenvironment of cell cultures is an ongoing challenge for many researchers. Much research has been conducted characterising individual aspects such as 3D architecture, mechanical properties, biochemicals, etc. The biggest deficits in existing models for monitoring analytes within the cellular environment is the lack of appropriate means for non invasive, real-time and integrated monitoring of the cellular responses. Nanosensors can overcome these issues: they are porous polymeric nanoparticles that are sensitive to a range of analytes including pH and O2. Microfabrication techniques are innovative tools to obtain controlled microstructures with a defined 3D architecture. In this work uniform sized 3D micro-scaled hydrogel constructs of approximately 300-400 um diameter were fabricated. Through dual incorporation of cells and nanosensors within these constructs we aim to have a real-time, non invasive method to measure microenvironmental pH value and O2 content. Ratiometric fluorescent output from the microenvironment is used to monitor O2 and pH during cell culture. Measurements show that 3D micro-scaled constructs are suitable for cell growth and proliferation. Moreover O2 content and pH within hydrogel cellularised microspheres are shown to have physiological values which enable the maintenance of the hepatic phenotype.

}, keywords = {Bioengineering, Nanotools}, author = {Tirella, A and A. Ahluwalia and Aylott, J and Carroll, L. A.} } @conference {1803, title = {A multi-stimuli environment for cardiac tissue engineering}, booktitle = {TERMIS 3rd World Congress}, year = {2012}, address = {Vienna, Austria}, abstract = {

The identification of the ideal cell source to generate cardiac tissue able to integrate into the host myocardium and with the contractile system is crucial for cardiac engineering. Amongst different cell sources so far proposed, human adult Cardiac Progenitor Cells (hCPCs) show the ability to proliferate and differentiate toward cardiac lineages when grown in appropriate microenvironmental conditions. It is widely accepted that conventional 2D cultures may provide a physiological environment for growing cells. For this reason the need to have an engineered microenvironment, matching physiological requirements, is crucial. A 3D context with spatial and time varying distribution of regulatory factors using mechanically matched scaffolds and bioreactors could represent an in vitro cell culture model being able to more closely reflects the in vivo conditions. In the present study, the possibility of using biocompatible and biodegradable scaffolds of collagen based or derivatives hydrogels in combination with Linneg/Sca-1pos hCPCs gathered from human heart biopsies was investigated. Bio-constructs were placed in the low shear, high flow MCmB (MultiCompartment modular Bioreactor) and the combined effects of dynamic culture conditions and 3D scaffolds on cell morphology and differentiation were studied in order to investigate the possibility of fabricating stem cell-derived cardiac patches to replace infarcted tissue.

}, keywords = {Bioengineering, Bioreactors, Dynamic 3D Cultures}, author = {Tirella, A and A. Ahluwalia and P. Di Nardo and Gaudiello, E and S. Giusti and F. Pagliari} } @conference {1797, title = {New method for the viscoelastic analysis of soft and highly hydrated biomaterials}, booktitle = {National Conference of Bioengineering}, year = {2012}, address = {Rome, Italy}, abstract = {

The role of materials mechanical properties is a new frontier for the evaluation of cell/material interaction, as well as for the determination of healthy/pathological state of a tissue. In these sense there is the need to have a unique method to measure materials viscoelastic properties. However, concerning with soft and highly hydrated constructs, the experimental set-up to precisely measure these properties is challenging because of the difficulty in defining zero stress or strain. To overcome these problems, we propose a novel and unique testing and data analysis technique (ERM) to derive materials viscoelastic properties. Results derived with this method can be compared to the ones obtained with standard testing techniques for viscoelastic materials. Pre-conditioning problems of testing soft and floppy materials are thus overcome, giving rise to have an accurate measure of viscous and elastic moduli of both hydrated materials and soft biological tissues. Small variations of measured properties can be also monitored with high precision, allowing a deeper investigation on the role of the scaffolding material or of tissue{\^a}{\texteuro}{\texttrademark}s extracellular matrix (respectively in cell culture systems or in biomechanics measurements for the characterisation of soft tissues).

}, keywords = {Bioengineering}, author = {Tirella, A and G. Mattei and A. Ahluwalia} } @article {1331, title = {The PAM2 system: a multilevel approach for fabrication of complex three-dimensional microstructures}, journal = {Rapid Prototyping Journal}, volume = {18}, year = {2012}, pages = {299{\textendash}307}, keywords = {Bioengineering}, doi = {10.1108/13552541211231725}, author = {Tirella, A and C. De Maria and G. Criscenti and G. Vozzi and A. Ahluwalia} } @article {1333, title = {Rapid Prototyping Composite and Complex Scaffolds with PAM2}, journal = {Methods in Molecular Biology}, volume = {868}, year = {2012}, pages = {57{\textendash}69}, keywords = {Bioengineering}, author = {G. Vozzi and Tirella, A and A. Ahluwalia} } @article {1334, title = {Realization of a poro-elastic ultrasound replica of pulmonary tissue}, journal = {Biomatter}, volume = {2}, year = {2012}, pages = {27{\textendash}26}, keywords = {Bioengineering}, url = {http://www.landesbioscience.com/journals/biomatter/article/19835/}, author = {Spinelli, A and Vinci, B. and Tirella, A and Matteucci, M and Gargani, L and A. Ahluwalia and C. Domenici and Picano, E and Chiarelli, P} } @conference {2283, title = {Replicating the 3D cardiomyocyte environment in the squeeze pressure bioreactor}, booktitle = {Journal of tissue engineering and regenerative medicine}, volume = {6 Suppl 1}, year = {2012}, pages = {341}, keywords = {Bioengineering}, doi = {10.1002/term.1586}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22941753}, author = {S. Giusti and Tirella, A and Galli, E and Vozzi, F. and Cabiati, M and A. Ahluwalia} } @conference {1792, title = {Replicating the cardiac environment in the Squeeze Pressure Bioreactor}, booktitle = {TERMIS 3rd World Congress}, year = {2012}, keywords = {Bioengineering}, author = {S. Giusti and Tirella, A and Galli, E and Vozzi, F. and Cabiati, M and A. Ahluwalia} } @article {1327, title = {Riboflavin and collagen: New crosslinking methods to tailor the stiffness of hydrogels}, journal = {Materials Letters}, volume = {74}, year = {2012}, pages = {58{\textendash}61}, 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.

}, keywords = {Bioengineering}, issn = {0167577X}, doi = {10.1016/j.matlet.2012.01.036}, url = {http://dx.doi.org/10.1016/j.matlet.2012.01.036}, author = {Tirella, A and Liberto, T and A. Ahluwalia} } @conference {1799, title = {How dimension a substrate for the realisation of controlled micro- and bio-inspired environment}, booktitle = {Euromat-FEMS}, year = {2011}, address = {Montpellier, France}, abstract = {

European Congress and Exhibition on Advanced Materials and Processes - Oral

}, keywords = {Bioengineering}, author = {Tirella, A and A. Ahluwalia and C. De Maria and Vozzi, F. and G. Vozzi and Sandri, T and Sassano, D and Cognolato, L} } @inbook {1789, title = {{Inherently Bio-Active Scaffolds: Intelligent Constructs to Model the Stem Cell Niche}}, booktitle = {Myocardial Tissue Engineering}, series = {Studies in Mechanobiology, Tissue Engineering and Biomaterials}, volume = {6}, year = {2011}, pages = {29{\textendash}47}, publisher = {Springer Berlin Heidelberg}, organization = {Springer Berlin Heidelberg}, address = {Berlin, Heidelberg}, abstract = {

The oft-abused phrase {\^a}{\texteuro}{\oe}genes load the gun, environment pulls the trigger{\^a}{\texteuro} can be applied to stem cells and stem cell niches as well as to cell{\^a}{\texteuro}{\textquotedblleft}material interfaces. Much is known about cell{\^a}{\texteuro}{\textquotedblleft}material interaction in general, perhaps a little less about how these interactions condition cell phenotype. With the increasing interest in stem cells and, in particular, their applications in tissue regeneration, the regulation of the stem cell microenvironment through modulation of intuitive or smart materials and structures, or what we term IBAS (Inherently Bio-Active Scaffolds) is poised to become a major field of research. Here, we discuss how cardiac regeneration strategies have undergone a gradual shift from the emphasis on biochemical signals and basic biology to one in which the material or scaffold plays a major role in establishing an equilibrium state. From being a constant battle or tug-of-war between the cells and synthetic environments, we conceive IBAS as intuitively responding to the cell{\^a}{\texteuro}{\texttrademark}s requirements to instate a sort of equilibrium in the system.

}, keywords = {Bioengineering}, isbn = {978-3-642-18055-2}, doi = {10.1007/978-3-642-18056-9}, url = {http://www.springerlink.com/content/j3k541l113233424/}, author = {P. Di Nardo and M. Minieri and Tirella, A and G. Forte and A. Ahluwalia}, editor = {Boccaccini, A. R. and Harding, S. E.} } @conference {1805, title = {Modelling and realisation of smart graded hydrogel scaffolds}, booktitle = {Euromat-FEMS}, year = {2011}, address = {Montpellier, France}, abstract = {

European Congress and Exhibition on Advanced Materials and Processes - Poster F12-P-2-08

}, keywords = {Bioengineering}, author = {Tirella, A and G. Mattei and F. Montemurro and G. Vozzi and A. Ahluwalia} } @article {1490, title = {PAM2 (Piston Assisted Microsyringe): A New Rapid Prototyping Technique for Biofabrication of Cell Incorporated Scaffolds}, journal = {Tissue Eng Part C Methods}, volume = {17}, year = {2011}, keywords = {Bioengineering}, doi = {10.1089/ten.tec.2010.0195}, author = {Tirella, A and Vozzi, F. and G. Vozzi and A. Ahluwalia} } @article {1488, title = {Substrate stiffness influences high resolution printing of living cells with an ink-jet system}, journal = {Journal of bioscience and bioengineering}, volume = {112}, year = {2011}, pages = {79{\textendash}85}, abstract = {

The adaptation of inkjet printing technology for the realisation of controlled micro- and nano-scaled biological structures is of great potential in tissue and biomaterial engineering. In this paper we present the Olivetti BioJet system and its applications in tissue engineering and cell printing. BioJet, which employs a thermal inkjet cartridge, was used to print biomolecules and living cells. It is well known that high stresses and forces are developed during the inkjet printing process. When printing living particles (i.e., cell suspensions) the mechanical loading profile can dramatically damage the processed cells. Therefore computational models were developed to predict the velocity profile and the mechanical load acting on a droplet during the printing process. The model was used to investigate the role of the stiffness of the deposition substrate during droplet impact and compared with experimental investigations on cell viability after printing on different materials. The computational model and the experimental results confirm that impact forces are highly dependent on the deposition substrate and that soft and viscous surfaces can reduce the forces acting on the droplet, preventing cell damage. These results have high relevance for cell bioprinting; substrates should be designed to have a good compromise between substrate stiffness to conserve spatial patterning without droplet coalescence but soft enough to absorb the kinetic energy of droplets in order to maintain cell viability.

}, keywords = {Bioengineering}, issn = {1347-4421}, doi = {10.1016/j.jbiosc.2011.03.019}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21497548}, author = {Tirella, A and Vozzi, F. and C. De Maria and G. Vozzi and Sandri, T and Sassano, D and Cognolato, L and A. Ahluwalia} } @conference {1532, title = {Enzymatic cross-linked hydrogel: role of Lysyl oxidase as an initiator of fibroblast inflammatory response}, booktitle = {Congresso Nazionale di Bioingegneria 2010}, year = {2010}, keywords = {Bioengineering}, author = {Tirella, A and G. Vozzi and N. Tirelli and A. Ahluwalia} } @article {1332, title = {Finite element modelling and design of a concentration gradient generating bioreactor: Application to biological pattern formation and toxicology}, journal = {Toxicology in vitro}, volume = {24}, year = {2010}, pages = {1828{\textendash}1837}, 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.

}, keywords = {Bioengineering}, issn = {1879-3177}, doi = {10.1016/j.tiv.2010.05.010}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20580814}, author = {G. Vozzi and D. Mazzei and Tirella, A and Vozzi, F. and A. Ahluwalia} } @conference {1527, title = {Hydrogel Bioactive Scaffold Fabricated with PAM2 System: Realization of Complex Shaped Scaffold with a Homogeneous Dispersion of HepG2 cells}, booktitle = {NIP Conference}, year = {2010}, keywords = {Bioengineering}, author = {Tirella, A and Vozzi, F. and G. Vozzi and A. Ahluwalia} } @conference {1531, title = {PAM2 microfabricated three-dimensional bioactive hydrogel systems: realisation of a hepatic-like structure}, booktitle = {Congresso Nazionale di Bioingegneria 2010}, year = {2010}, keywords = {Bioengineering}, author = {Tirella, A and Vozzi, F. and Vinci, B. and G. Vozzi and A. Ahluwalia} } @conference {1525, title = {PAM2 System: a Modular Approach for the Realisation of Complex Shaped Scaffold Able to Reproduce the Main Features of a Specific Micro-environment,}, booktitle = {2010 International Conference on Biofabrication, 4-6 October 2010, Philadelphia, USA}, year = {2010}, keywords = {Bioengineering}, author = {A. Ahluwalia and Tirella, A and G. Vozzi} } @inbook {1522, title = {Rapid Prototyping Composite and Complex Scaffolds with PAM2}, booktitle = {Computer-Aided Tissue Engineering}, volume = {868}, number = {Methods in Molecular Biology}, year = {2010}, pages = {57-69}, chapter = {Rapid Prototyping Composite and Complex Scaffolds with PAM2}, keywords = {Bioengineering}, author = {G. Vozzi and Tirella, A and A. Ahluwalia} } @conference {1526, title = {Site Specific Nano-Tuning of Scaffolds Using Inkjet Printing}, booktitle = {NIP Conference}, year = {2010}, address = {Austin, Texas }, keywords = {Bioengineering}, author = {Tirella, A and F. Montemurro and Vinci, B. and Vozzi, F. and G. Vozzi and Sassano, D and Sandri, T and Cognolato, L and A. Ahluwalia} } @article {1328, title = {A phase diagram for microfabrication of geometrically controlled hydrogel scaffolds}, journal = {Biofabrication}, volume = {1}, year = {2009}, pages = {045002}, 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.

}, keywords = {Bioengineering}, issn = {1758-5090}, doi = {10.1088/1758-5082/1/4/045002}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20811111}, author = {Tirella, A and Orsini, A and G. Vozzi and A. Ahluwalia} } @conference {1795, title = {Pneumatic module of PAM2 microfabrication system: realization of bio-inspired complex scaffolds}, booktitle = {3B International Conference in Bioprinting and Biofabrication}, year = {2009}, address = {Bordeaux, France}, abstract = {

poster

}, keywords = {Bioengineering}, author = {C. De Maria and Tirella, A and A. Ahluwalia and G. Vozzi} } @conference {1642, title = {Biomimicry of PAM Microfabricated Hydrogel Scaffolds}, booktitle = {International Conference on Digital Printing Technologies Conference Proceedings}, year = {2008}, pages = {{\textendash}}, keywords = {Bioengineering}, author = {Tirella, A and G. Vozzi and A. Ahluwalia} } @conference {1640, title = {Microfabbricazione di scaffold in alginato con propriet{\`a}~ meccaniche modulabili}, booktitle = {Congresso Nazionale Biomateriali 2008}, year = {2008}, pages = {{\textendash}}, keywords = {Bioengineering}, author = {Orsini, A and Tirella, A and A. Ahluwalia and G. Vozzi} } @conference {1634, title = {Microfabrication of Hydrogels scaffolds including cells and mechanical characterization}, booktitle = {Congresso Nazionale di Bioingegneria 2008}, year = {2008}, pages = {367-368}, address = {Pisa, Italy}, keywords = {Bioengineering}, author = {Tirella, A and G. Vozzi} } @conference {1794, title = {Microfluidic Gradient Maker for Pattern Generation}, booktitle = {TERMIS-EU}, year = {2008}, pages = {879}, address = {Porto, Portugal}, abstract = {

poster

}, keywords = {Bioengineering}, author = {Tirella, A and D. Mazzei and G. Vozzi and A. Ahluwalia} } @article {1489, title = {A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine}, journal = {Toxicology in vitro}, volume = {22}, year = {2008}, pages = {1957{\textendash}64}, abstract = {

A great deal of effort is being dedicated to the development of new devices able to conduct effective in vitro toxicology analyses. This paper describes the use of a microfluidic gradient maker for the toxicological analysis of two conventional local anesthetics, bupivacaine and lidocaine on cell cultures. The microfluidic device was designed and simulated using COMSOL Multiphysics and the concentration gradient in the microfluidic network was analysed through a fluidodynamic and diffusive study. Subsequently the device was fabricated with soft lithography, casting PDMS in a master to obtain channels about 250 microm deep. Both drugs were 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 system was critically compared with microwell-based toxicity testing. The results show that the GM 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. However, the flow rates required to obtain a suitable concentration range across the device may damage shear sensitive cells.

}, keywords = {Bioengineering}, issn = {0887-2333}, doi = {10.1016/j.tiv.2008.09.016}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18940244}, author = {Tirella, A and Marano, M and Vozzi, F. and A. Ahluwalia} } @conference {1796, title = {PAM Composite Scaffold of PCL and Carbon NanoTubes for Bone Tissue Regeneration}, booktitle = {National Conference of Bioengineering}, year = {2008}, pages = {369}, address = {Pisa, Italy}, abstract = {

poster

}, keywords = {Bioengineering}, author = {Mattioli-Belmonte, M. and Fantauzzi, V and K KYRIAKIDOU and Tirella, A and A. Ahluwalia and G. Vozzi} } @conference {1641, title = {Realizzazione di strutture micro fabbricate tramite tecnica di micro Laser Sintering per applicazione alla Tissue Engineering}, booktitle = {Congresso Nazionale Biomateriali 2008}, year = {2008}, pages = {{\textendash}}, keywords = {Bioengineering}, author = {G. Criscenti and Tirella, A and A. Ahluwalia and P. Giusti and G. Vozzi} }