03563nas a2200205   4500008004100000022002200041245010600063210006900169260003300238300001400271520283400285653001903119100001503138700001403153700001403167700001803181700001703199700001703216856012403233       2011                        eng d  a978-1-62100-164-500aMulti-Compartmental Modular Bioreactor as Innovative System for Dynamic Cell Cultures and Co-Cultures0 aMultiCompartmental Modular Bioreactor as Innovative System for D  bNova Science Publishers, Inc  a159 - 1783 a<p>In this chapter, the design, fabrication process and preliminary tests of a Multi- Compartmental Modular Bioreactor used as a system for dynamic cell cultures and co-cultures is described. Although the microwell (MW) plate has become a standard in cell culture, the complexity of the physiological environment is not replicated in petri dishes or microplates. All cells are exquisitely sensitive to their micro-environment which is rich with cues from other cells and from mechanical stimuli due to flow, perfusion and movement. Microwells do not offer any form of dynamic chemical or physical stimulus to cells, such as concentration gradients, flow, pressure or mechanical stress. This is a major limitation in experiments investigating cellular responses in-vitro since the complex interplay of mechanical and biochemical factors is absent. Most researchers and industry have started to accept that classical in vitro experiments offer poor predictive value or mechanistic understanding and are shifting their interests to new technologies such as bioreactors. For this reason, a large number of bioreactor systems for cell culture have been recently designed and described. With the purpose of developing cell culture models to establish a physiological-like interaction between different cell types, a novel Multi-Compartmental Modular Bioreactor (MCmB)was realized. The modular chamber was designed with shape and dimensions similar to the 24-MultiWell allowing an easy transfer of microwell protocols. The MCmB consists of a cell culture chamber made of bio-compatible silicon polymer, with excellent self-sealing proprieties, transparency and flexibility. The modular chambers can be also connected together in series or in parallel as desired, in order to allow cell-cell cross-talk or replicate in vitro models of metabolism or diseases using allometric design principles. In this chapter we describe the bioreactor design process starting from a finite-element method (FEM) model, developed in order to study the shear stress and the oxygen concentration at the cell surface. A further version of the MCmB is also described, in which a semipermeable membrane is placed into the bioreactor allowing to create a double-chamber system (MCmB-dc) for biological barriers simulation like for example lung or intestine. Allometric methods for designing in-vitro organ models using combinations of different cell types or tissues cultured in different chambers are also presented. Allometric laws mathematically correlate non linear quantities such as organ mass, blood flow, blood retention time and metabolic rate. Using these laws the modules can be assembled in various configurations enabling organ and system physiology to be recapitulated in vitro. Preliminary experiments using the modules are also described.</p>
10aBioengineering1 aMazzei, D.1 aGiusti, S1 aSbrana, T1 aAhluwalia, A.1 aAntolli, P G1 aLiu, Zhiming  uhttp://95.110.227.47/publications/multi-compartmental-modular-bioreactor-innovative-system-dynamic-cell-cultures-and-co04733nas a2200181   4500008004100000245014100041210006900182260004800251300001400299520406100313653001904374100001404393700001804407700001704425700001704442700001204459856008004471       2011                        eng d00aThe Squeeze Pressure Bioreactor: Design and Modelling of a Non-Contact Device for Mechanical Stimulation of Tissue Engineered Constructs0 aSqueeze Pressure Bioreactor Design and Modelling of a NonContact  aHauppauge NYbNova Science Publishers, Inc.  a199–2143 a<p>Diseases of hyaline cartilage represent one of the major health problems, especially in industrialized countries with high life expectancy. The erosion of the articulating surfaces of joints, known as osteoarthritis, currently affects more than 200 million citizens worldwide, and more than 50% of the patients need or will need a surgical treatment. Articular cartilage is a three dimensional avascular tissue, which covers the ends of all synovial joints. During normal daily function, articular cartilage can be repeatedly subjected to forces up to several time body weight, but it is able to provide articulating joints with a nearly frictionless motion. Despite its tremendously important function, articular cartilage has limited capacity for auto regeneration after degenerative and rheumatic diseases, like arthritis, as well as traumatic injuries. Cartilage problems are a huge and still unsolved medical issue, which therefore represents one of the most important tissue engineering targets requiring high quality products as fast as possible. For this reason, the possibility to recreate in vitro cartilage substitutes as a real alternative to total joint replacement represents an increasing and hopeful market, in which many research groups are still working. At the moment, one of the main findings in invitro cartilage studies is the importance of the role of mechanical stimuli and dynamic loads for the chondrocytes growth and differentiation. Several studies using cartilage explants or chondrocytes seeded in 3D scaffolds have shown that mechanical compressive loads affect the cells metabolic activity and their matrix production. In order to simulate the in vivo environment, the use of bioreactors is becoming fundamental: bioreactors can provide the chemical and mechanical signals that optimize tissue development. Furthermore, bioreactors could be an important instrument to reduce the cost of clinical studies, used as in vitro predictors of in vivo performance. In this way,the use of bioreactors can reduce animal studies, helping the scientists to focus their attention in the right direction before starting pre-clinical studies, which are usually more expensive than preliminary research. In the past few years, several systems for the application of different mechanical stimuli to chondrocytes have been developed. Most of these can generate biomechanical-like forces such as the direct compression, tensile and shear forces, or hydrostatic pressure, in order to stimulate the articular chondrocyctes to increase their matrix production. Generally, the most important requirements that a culture system has to satisfy are high reliability and usability, perfect sterility, easy control of all the important culture parameters and low cost. In this work, a new system, inspired by the synovial environment of mobile joints and able to apply an innovative type of stimulation on articular chondrocytes is described and modeled. The SQPR (SQueeze PRessure) bioreactor chamber is designed to impose a cyclic hydrodynamic pressure on cell cultures, constructs or tissues slices. The basic principle of this new system is the generation of a localized contact less overpressure on articular chondrocytes, using a simple vertical piston movement. This kind of stimulation is particularly useful for neo-tissue or fresh-constructs, in which cells require a dynamic environment to maintain their differentiate state, but at the same time do not tolerate direct compression or high shear stress. When the piston moves down, a controlled hydrodynamic overpressure and a shear stress is generated over the cell surface, stimulating the chondrocytes to improve their matrix production. The fluid dynamics inside the SQPR bioreactor is illustrated from an analytical and numerical point of view. We show how these models can predict the pressure, velocity field and wall shear stress generated on the cell surface of the construct. The bioreactor design is presented in detail and validation tests on chondrocytes are described.</p>
10aBioengineering1 aGiusti, S1 aAhluwalia, A.1 aDe Maria, C.1 aAntolli, P G1 aLiu, Z.  uhttps://www.novapublishers.com/catalog/product\_info.php?products\_id=22653